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5.4: Cardiac Cycle - Biology

5.4: Cardiac Cycle - Biology


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Learning Objectives

By the end of this section, you will be able to:

  • Describe the relationship between blood pressure and blood flow
  • Summarize the events of the cardiac cycle
  • Compare atrial and ventricular systole and diastole
  • Relate heart sounds detected by auscultation to action of heart’s valves

The period of time that begins with contraction of the atria and ends with ventricular relaxation is known as the cardiac cycle. The period of contraction that the heart undergoes while it pumps blood into circulation is called systole. The period of relaxation that occurs as the chambers fill with blood is called diastole. Both the atria and ventricles undergo systole and diastole, and it is essential that these components be carefully regulated and coordinated to ensure blood is pumped efficiently to the body.

Pressures and Flow

Fluids, whether gases or liquids, are materials that flow according to pressure gradients—that is, they move from regions that are higher in pressure to regions that are lower in pressure. Accordingly, when the heart chambers are relaxed (diastole), blood will flow into the atria from the veins, which are higher in pressure. As blood flows into the atria, the pressure will rise, so the blood will initially move passively from the atria into the ventricles. When the action potential triggers the muscles in the atria to contract (atrial systole), the pressure within the atria rises further, pumping blood into the ventricles. During ventricular systole, pressure rises in the ventricles, pumping blood into the pulmonary trunk from the right ventricle and into the aorta from the left ventricle. Again, as you consider this flow and relate it to the conduction pathway, the elegance of the system should become apparent.

Phases of the Cardiac Cycle

At the beginning of the cardiac cycle, both the atria and ventricles are relaxed (diastole). Blood is flowing into the right atrium from the superior and inferior venae cavae and the coronary sinus. Blood flows into the left atrium from the four pulmonary veins. The two atrioventricular valves, the tricuspid and mitral valves, are both open, so blood flows unimpeded from the atria and into the ventricles. Approximately 70–80 percent of ventricular filling occurs by this method. The two semilunar valves, the pulmonary and aortic valves, are closed, preventing backflow of blood into the right and left ventricles from the pulmonary trunk on the right and the aorta on the left.

Atrial Systole and Diastole

Contraction of the atria follows depolarization, represented by the P wave of the ECG. As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum, pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular (tricuspid, and mitral or bicuspid) valves. At the start of atrial systole, the ventricles are normally filled with approximately 70–80 percent of their capacity due to inflow during diastole. Atrial contraction, also referred to as the “atrial kick,” contributes the remaining 20–30 percent of filling (see the image below). Atrial systole lasts approximately 100 ms and ends prior to ventricular systole, as the atrial muscle returns to diastole.

Ventricular Systole

Ventricular systole (see image below) follows the depolarization of the ventricles and is represented by the QRS complex in the ECG. It may be conveniently divided into two phases, lasting a total of 270 ms. At the end of atrial systole and just prior to atrial contraction, the ventricles contain approximately 130 mL blood in a resting adult in a standing position. This volume is known as the end diastolic volume (EDV) or preload.

Initially, as the muscles in the ventricle contract, the pressure of the blood within the chamber rises, but it is not yet high enough to open the semilunar (pulmonary and aortic) valves and be ejected from the heart. However, blood pressure quickly rises above that of the atria that are now relaxed and in diastole. This increase in pressure causes blood to flow back toward the atria, closing the tricuspid and mitral valves. Since blood is not being ejected from the ventricles at this early stage, the volume of blood within the chamber remains constant. Consequently, this initial phase of ventricular systole is known as isovolumic contraction, also called isovolumetric contraction (see image below).

In the second phase of ventricular systole, the ventricular ejection phase, the contraction of the ventricular muscle has raised the pressure within the ventricle to the point that it is greater than the pressures in the pulmonary trunk and the aorta. Blood is pumped from the heart, pushing open the pulmonary and aortic semilunar valves. Pressure generated by the left ventricle will be appreciably greater than the pressure generated by the right ventricle, since the existing pressure in the aorta will be so much higher. Nevertheless, both ventricles pump the same amount of blood. This quantity is referred to as stroke volume. Stroke volume will normally be in the range of 70–80 mL. Since ventricular systole began with an EDV of approximately 130 mL of blood, this means that there is still 50–60 mL of blood remaining in the ventricle following contraction. This volume of blood is known as the end systolic volume (ESV).

Ventricular Diastole

Ventricular relaxation, or diastole, follows repolarization of the ventricles and is represented by the T wave of the ECG. It too is divided into two distinct phases and lasts approximately 430 ms.

During the early phase of ventricular diastole, as the ventricular muscle relaxes, pressure on the remaining blood within the ventricle begins to fall. When pressure within the ventricles drops below pressure in both the pulmonary trunk and aorta, blood flows back toward the heart, producing the dicrotic notch (small dip) seen in blood pressure tracings. The semilunar valves close to prevent backflow into the heart. Since the atrioventricular valves remain closed at this point, there is no change in the volume of blood in the ventricle, so the early phase of ventricular diastole is called the isovolumic ventricular relaxation phase, also called isovolumetric ventricular relaxation phase (see image below).

In the second phase of ventricular diastole, called late ventricular diastole, as the ventricular muscle relaxes, pressure on the blood within the ventricles drops even further. Eventually, it drops below the pressure in the atria. When this occurs, blood flows from the atria into the ventricles, pushing open the tricuspid and mitral valves. As pressure drops within the ventricles, blood flows from the major veins into the relaxed atria and from there into the ventricles. Both chambers are in diastole, the atrioventricular valves are open, and the semilunar valves remain closed (see image below). The cardiac cycle is complete. Figure 2 illustrates the relationship between the cardiac cycle and the ECG.

Heart Sounds

One of the simplest, yet effective, diagnostic techniques applied to assess the state of a patient’s heart is auscultation using a stethoscope.

In a normal, healthy heart, there are only two audible heart sounds: S1 and S2. S1 is the sound created by the closing of the atrioventricular valves during ventricular contraction and is normally described as a “lub,” or first heart sound. The second heart sound, S2, is the sound of the closing of the semilunar valves during ventricular diastole and is described as a “dub” (Figure 3). In both cases, as the valves close, the openings within the atrioventricular septum guarded by the valves will become reduced, and blood flow through the opening will become more turbulent until the valves are fully closed. There is a third heart sound, S3, but it is rarely heard in healthy individuals. It may be the sound of blood flowing into the atria, or blood sloshing back and forth in the ventricle, or even tensing of the chordae tendineae. S3 may be heard in youth, some athletes, and pregnant women. If the sound is heard later in life, it may indicate congestive heart failure, warranting further tests. Some cardiologists refer to the collective S1, S2, and S3 sounds as the “Kentucky gallop,” because they mimic those produced by a galloping horse. The fourth heart sound, S4, results from the contraction of the atria pushing blood into a stiff or hypertrophic ventricle, indicating failure of the left ventricle. S4 occurs prior to S1 and the collective sounds S4, S1, and S2 are referred to by some cardiologists as the “Tennessee gallop,” because of their similarity to the sound produced by a galloping horse with a different gait. A few individuals may have both S3 and S4, and this combined sound is referred to as S7.

The term murmur is used to describe an unusual sound coming from the heart that is caused by the turbulent flow of blood. Murmurs are graded on a scale of 1 to 6, with 1 being the most common, the most difficult sound to detect, and the least serious. The most severe is a 6. Phonocardiograms or auscultograms can be used to record both normal and abnormal sounds using specialized electronic stethoscopes.

During auscultation, it is common practice for the clinician to ask the patient to breathe deeply. This procedure not only allows for listening to airflow, but it may also amplify heart murmurs. Inhalation increases blood flow into the right side of the heart and may increase the amplitude of right-sided heart murmurs. Expiration partially restricts blood flow into the left side of the heart and may amplify left-sided heart murmurs. Figure 4 indicates proper placement of the bell of the stethoscope to facilitate auscultation.

Chapter Review

The cardiac cycle comprises a complete relaxation and contraction of both the atria and ventricles, and lasts approximately 0.8 seconds. Beginning with all chambers in diastole, blood flows passively from the veins into the atria and past the atrioventricular valves into the ventricles. The atria begin to contract (atrial systole), following depolarization of the atria, and pump blood into the ventricles. The ventricles begin to contract (ventricular systole), raising pressure within the ventricles. When ventricular pressure rises above the pressure in the atria, blood flows toward the atria, producing the first heart sound, S1 or lub. As pressure in the ventricles rises above two major arteries, blood pushes open the two semilunar valves and moves into the pulmonary trunk and aorta in the ventricular ejection phase. Following ventricular repolarization, the ventricles begin to relax (ventricular diastole), and pressure within the ventricles drops. As ventricular pressure drops, there is a tendency for blood to flow back into the atria from the major arteries, producing the dicrotic notch in the ECG and closing the two semilunar valves. The second heart sound, S2 or dub, occurs when the semilunar valves close. When the pressure falls below that of the atria, blood moves from the atria into the ventricles, opening the atrioventricular valves and marking one complete heart cycle. The valves prevent backflow of blood. Failure of the valves to operate properly produces turbulent blood flow within the heart; the resulting heart murmur can often be heard with a stethoscope.

Self Check

Answer the question(s) below to see how well you understand the topics covered in the previous section.

Critical Thinking Question

Describe one cardiac cycle, beginning with both atria and ventricles relaxed.

[practice-area rows=”4″][/practice-area]
[reveal-answer q=”324052″]Show an Example Answer[/reveal-answer]
[hidden-answer a=”324052″]The cardiac cycle comprises a complete relaxation and contraction of both the atria and ventricles, and lasts approximately 0.8 seconds. The atria begin to contract following depolarization of the atria and pump blood into the ventricles. The ventricles begin to contract, raising pressure within the ventricles. When ventricular pressure rises above the pressure in the two major arteries, blood pushes open the two semilunar valves and moves into the pulmonary trunk and aorta in the ventricular ejection phase. Following ventricular repolarization, the ventricles begin to relax, and pressure within the ventricles drops. When the pressure falls below that of the atria, blood moves from the atria into the ventricles, opening the atrioventricular valves and marking one complete heart cycle.[/hidden-answer]

Glossary

cardiac cycle period of time between the onset of atrial contraction (atrial systole) and ventricular relaxation (ventricular diastole)

diastole:: period of time when the heart muscle is relaxed and the chambers fill with blood

end diastolic volume (EDV): (also, preload) the amount of blood in the ventricles at the end of atrial systole just prior to ventricular contraction

end systolic volume (ESV): amount of blood remaining in each ventricle following systole

heart sounds: sounds heard via auscultation with a stethoscope of the closing of the atrioventricular valves (“lub”) and semilunar valves (“dub”)

isovolumic contraction: also, isovolumetric contraction) initial phase of ventricular contraction in which tension and pressure in the ventricle increase, but no blood is pumped or ejected from the heart

isovolumic ventricular relaxation phase: initial phase of the ventricular diastole when pressure in the ventricles drops below pressure in the two major arteries, the pulmonary trunk, and the aorta, and blood attempts to flow back into the ventricles, producing the dicrotic notch of the ECG and closing the two semilunar valves

murmur: unusual heart sound detected by auscultation; typically related to septal or valve defects

preload: (also, end diastolic volume) amount of blood in the ventricles at the end of atrial systole just prior to ventricular contraction

systole: period of time when the heart muscle is contracting

ventricular ejection phase: second phase of ventricular systole during which blood is pumped from the ventricle


Table 1 – Pressures observed within cardiac chambers during systole and diastole
Heart region Pressure (mmHg)
Right atrium 0-4
Right ventricle 25 systolic 4 diastolic
Pulmonary artery 25 systolic 10 diastolic
Left atrium 8-10
Left ventricle 120 systolic 10 diastolic
Aorta 120 systolic 80 diastolic

The above table shows the range of pressures present throughout the heart during the cardiac cycle. Knowing these values can help us understand the progression between different stages of the cycle. For example, the pulmonary artery has a systolic pressure of 25mmHg, so the right ventricle must match this force to successfully eject blood.


5.4: Cardiac Cycle - Biology

C2006/F2402 '05 Outline for Lecture 22 (c) 2005 Deborah Mowshowitz

Last Update: 04/20/2005 10:19 AM .

Handouts: 22A (Heart Action Potentials) 22B (Heart Structure & Circulation) 22C (as Exchange -- to be covered next time) 22D -- Smooth Muscle Structure. Handouts are not on web extras are in boxes outside 700 Mudd.

Some Nice Web Links on the Heart

Additional reading:

Medical reference:

  • American Heart Association. All-around good site for information on heart disease and heart health.
  • Heartpoint. An excellent compilation of information on heart disease, as well as advice on heart-healthy living.

A. What use is smooth muscle? What unique properties does it have?

1. Location -- much of it makes up walls of hollow organs & tubes. Maintains shape and pushes contents along.

2. Contraction speed & rate of fatigue -- relatively slow.

3. Latch state possible -- can remain contracted for prolonged period without input of ATP. (One ATP split per bridge cycle, but cycle is much slower.)

4. Length over which it contracts/stretch es -- relatively long.

5. Contracts/relaxes in response to many different stimuli -- nerves, hormones, stretch, etc.

Overall: Can integrate multiple signals and maintain "tone" over wide range of length with economical use of ATP.

B. Ca ++ triggers contraction

1. Role of Ca ++ : State of thick filaments, not state of thin, are affected by Ca ++ .

2. Where Ca ++ comes from
:

a. Most Ca ++ comes from outside of cell. Neurotransmitters, hormones etc. open Ca ++ channels in plasma membrane using second messengers, and Ca ++ comes in from extracellular fluid (ECF). In some smooth muscles, voltage gated Ca ++ channels open and generate an AP.

b. A little Ca ++ is released by the ER. (See "Ca ++ induced Ca release," described below.)

1. Smooth muscle contains no troponin (does have tropomyosin, but doesn't block actin-myosin binding sites)

2. Arrangement of actin/myosin bundles -- see handout 22D, bottom.

3. Intermediate filaments -- connect dense bodies & help hold bundles in place. (Dense body = same function as Z line in skeletal muscle.)

4. No T tubules.

5. Two Types.

a. Single Unit smooth muscle -- the cells are connected by gap junctions and contract as a unit.

b. Multi unit smooth muscle -- the cells are not coupled electrically cells are stimulated and contract individually.

D. Calmodulin controls contraction/Ca ++ response (instead of troponin). See Becker fig. 23-24 & Handout 22D, middle.

1. Calmodulin-Ca ++ complex forms

2. Calmodulin--Ca ++ complex binds to and activates a kinase (MLCK)

3. Kinase phosphorylates and activates myosin (so it can bind actin)

D. Actin accessibility may be regulated by other factors, but not Ca ++

E. Cross bridge Cycle -- Can maintain stable cross bridges for a long time without breaking ATP (because of slow bridge cycle -- slow ATPase and slower Ca ++ pump. Still need one ATP used per cross bridge made/broken.)

F. Speed -- contraction is slower than with skeletal, because:

1. A component requires phosphorylation before bridge cycle can begin

2. ATPase of myosin slower get slower contraction (slower bridge cycle) but less fatigue

G. Trigger for contraction -- innervation & hormones

1. Autonomic system and/or hormones , not somatic (as for skeletal).

a. Stimulus can be excitatory or inhibitory.

(1). Hormones and autonomic neurotransmitters from postganglionic neurons affect channels & pumps indirectly using 2nd messengers. (Compare to situation with nerve/muscle synapse.)

(2). Examples in previous lectures: epinephrine can cause smooth muscle contraction (through IP3) or relaxation (through cAMP and Ca ++ pump). Response depends on receptors on smooth muscle.

b. Stimulus can generate an action potential (to open Ca ++ channels) or act through a second messenger to affect Ca ++ levels (w/o going through an AP). See examples above.

c. An external stimulus may not be needed. Some smooth muscles have pacemaker cells that generate an AP spontaneously. Autonomic and/or hormonal stimulation modulate effects of internal signals from pacemakers.

2. Structure of nerve/muscle synapse is different -- neurons have multiple varicosities (points of contact with smooth muscle -- contain vesicles of neurotransmitter), and muscle has no complex structure at synapse (no motor endplate). One autonomic neuron can stimulate multiple smooth muscle cells &/or multiple points on a single muscle cell. See handout 22D, top. One smooth muscle cell (or single unit smooth muscle) can get input from both PS and S.

Try problem 9-1, parts C & D, and try answering question 9-4 for the case of smooth muscle. If we finish smooth muscle, you should be able to do all of the problems in set 9.

1. Bridge cycle etc. much like skeletal . See below for details of Ca ++ role.

2. Similar to oxidative/slow twitch skeletal -- low fatigue rate but very oxygen dependent.

3. Cells are coupled electrically (gap junctions at intercalated disks)

4. Special features of AP in membrane (see handout 22-A)

a. AP lasts much longer (as long as contraction) so tetany is impossible. Each contraction ends before next AP arrives. (see fig. 14-15 on handout & 47.7 & 49.8 (47.11) of Purves)

b. Prolonged AP (long depolarized phase) is due to delay in opening slow voltage gated K+ gates and opening of Ca ++ channels. (see fig. 14-14 on handout & 49.8 in Purves.)

5. Role of Pacemakers. Trigger for contraction is signal from pacemaker cells of heart, not from AP of nerve. (Autonomic neurons release transmitters that slow or speed up contractions see below.)

B. Pacemaker cells -- found in heart and some smooth muscle -- see handout 22-A (fig. 14-16) or Purves 49.6 (49.7).

1. Set pace of heart beat

2. Fire spontaneously

3. Depolarize slowly to threshold --> pacemaker potential ---> AP when reaches threshold.

Overall cause of slow depolarization in heart: more Na + and Ca ++ leak in, and less K + leaks out, gradually depolarizing the cell. The movement of ions is controlled by multiple channels -- see handouts and below.

4. Channels involved: T he ion flows & channels that generate the pacemaker potential are quite complex. Here are some of the critical points see advanced texts if you are interested in more details.

a. If channels: Na + goes through a Na + /K + channel similar to one ---> EPSP. This channel = If channel on handout 22A. Na + leaks in slowly, depolarizing the cell to threshold. The If channels are called "funny" channels because they open when the cell is hyperpolarized, not when it is depolarized.

b. K + leak channels: The slow depolarization during the pacemaker potential is caused by the closing of K + leak channels out of the cell, in addition to the opening of If channels that allow Na + in. Since the K + flow out (through leak channels) is reduced, the slight Na + leak in (through the If channels) depolarizes the cell. If the K + leak channels remain open, they can counterbalance the effects of Na + leakage. Transmitters and/or hormones can alter the state of the leak channels &/or the If channels, as explained below.

c. Ca ++ channels are also involved in the late phases of the pacemaker potential.

5. Role of Autonomic innervation. S/PS release transmitters --> open/shut K + leak channels, Ca ++ channels and/or the If channels --> faster or slower depolarization = steeper or flatter pacemaker potential ---> pacemaker cells fire AP sooner or later --> faster or lower heartbeat. (see Purves 49.6 (49.7))

Note: Transmitters may also affect the threshold value needed to fire an AP and/or the maximum hyperpolarization of the pacemaker cells -- this can also affect the time between AP's. (See advanced texts if you are interested.)

6. AP (spike in potential) in pacemaker cells is largely due to inrush of Ca ++ not Na + . (see fig. 14-6, panel (c) on handout 22A). When cells depolarize to threshold, voltage gated Ca ++ channels, not voltage gated Na + channels, are opened.

See Problems 11-1 & 11-2.

C. Excitation-Contraction Coupling -- how AP in muscle plasma membrane leads to cross bridge activity within the muscle.

1. What occurs in both cardiac & skeletal muscle:

a. AP in muscle membrane travels into T tubules.

b. Proteins in T tubule membrane are activated (change conformation) in response to voltage differences.

c. Activated receptors in T tubule trigger opening of Ca ++ channels in ER/SR. ( How DHP receptors open channels in ER is different between the two muscle types -- linkage is mechanical in skeletal muscle through Ca ++ release in cardiac muscle. See below.)

d. Ca ++ released from ER/SR.

e. Increase in cytoplasmic Ca ++ triggers start of cross bridge cycle.

f. Contraction ends when Ca ++ removed. (Ca ++ is sent back where it came from -- Pumped back into ER or out of cell using ATP.)

2. What's different in cardiac muscle

a. Voltage activated proteins in membrane are Ca ++ channels.

b. AP triggers opening of the Ca ++ channels in T tubule Small amount of Ca ++ from extracellular fluid (ECF) in T tubule enters cytoplasm.

c. "Ca ++ induced Ca release": Small amount of Ca ++ from ECF binds to receptors on surface of ER and opens Ca ++ channels in ER/SR --> release of large amounts of Ca ++ into cytoplasm. (Occurs in smooth muscle, too but amount of Ca ++ release from ER not as significant.)

FYI: The voltage activated proteins in the plasma membrane referred to above are usually called DHP or dihyropyridine receptors. In smooth and cardiac muscle, the DHP receptors are also Ca ++ channels. The Ca ++ channels in the ER are called ryanodine receptors. (The names come from inhibitors that bind to the respective proteins.) The DHP and ryanodine receptors are coupled in all three types of muscle, but the mechanism of coupling is different.

3. What's different in smooth muscle? No T tubules Ca ++ mostly comes from outside the cell. Small amount of "Ca ++ induced Ca release" from ER by same mechanism as for cardiac muscle.

III. Heart Structure & Function (See handout 22B). Where are the contractile and pacemaker cells?

A. Structure of heart -- Purves Fig. 49.3 (49.4) -- note all pictures show person facing you, so "right" 1/2 of heart is on left of picture. "Subway diagrams" on top and bottom show what is connected to what, and how overall blood flow goes, but no real anatomy. Pictures in middle show approximations of actual structures.

B. Position, function of pacemaker cells (nodes), bundle of His, Purkinje fibers -- see Purves fig. 49.7 (49.8) & handout middle right.

1. All these cells have pacemaker activity -- make up the conduction system -- carry the AP to all parts of the heart.

2. SA node usually in charge. SA node has the fastest firing rhythm -- normally controls heart beat. Fires first.

3. Role of AP in SA node. Causes atria to contract, pushing blood into ventricles. Causes AV node to fire after a short delay

4. AP in AV node spreads to bundle of His and Purkinje fibers

5. Bundle of His etc. causes ventricles to contract , from bottom up, pushing blood out top of heart.

See Problems 11--3, 11-4, & 11-6.

C. Overall view of circulation -- see handout 22B and Purves p. 945 (870).

1. There are 2 loops of circulation -- to lungs (pulmonary) and to body (systemic) -- see picture on bottom. Different blood vessels go in parallel to various parts of body. (Helps to compare all pictures on 22B to understand the structure of heart and circulation.)

2. Arteries go away from the heart don't necessarily carry oxygenated blood

3. Structure: Arteries and veins, arterioles and venules are surrounded by smooth muscle capillaries are not.

4. Cardiac cycle -- systole & diastole

a. Systole -- ventricles contract ("squeeze"), blood pumped out to system

b. Diastole -- ventricles relax fill with blood

c. Note: the terms systole (contraction) and diastole (relaxation) can be used to refer to the state of the ventricles or to the state of the atria. In common usage, the terms always refer to the state of the ventricles.

See problem 11-5.

IV. Gas Exchange -- how do you get O2 to cells and CO2 to lungs? See Gas Exchange handouts (22C & D) & Purves 48.14 (48.17).

A. Exchange (of oxygen, carbon dioxide & other nutrients and waste) at capillaries. (For structures see Purves fig.48-10 (48-12) or handout 22D.

1. In lungs: materials in alveoli exchange with materials in pulmonary capillaries

2. In tissues: materials in cells exchange with materials in systemic capillaries

3. Structure: capillaries have large surface area and slow flow of blood, promoting exchange

Rest of material will be covered next time.

1. Hemoglobin (Hb) binds & traps O2 in red blood cell (RBC) at lungs (See handout 22C, panel B)

2. Hb releases O2 in tissues (See handout 22C, panel D)

3. Hb has many important properties that enable it to function properly if time some will be discussed next time.

C. How is CO2 carried? See handout 22C panels A & C or Purves fig. 48.14 (48.17)

1. What happens in tissues? (panel C on 22-C)

a. CO2 from metabolism enters RBC

b. Inside RBC, carbonic anhydrase (one of fastest enzymes known turn over # of 6 X 10 5 /sec) converts CO2 to carbonic acid. Traps CO2.

c. Carbonic acid disassociates into bicarbonate and H + . (This is not actually a separate step -- enzyme directly generates bicarb.)

d. Anion exchanger (band 3 protein) switches bicarb (in cell) for Cl- in blood.

e. Some CO2 and H + binds to Hb (deoxygenated)

2. What happens in lungs? (Panel A on 22-C)

a. Process described above reverses -- bicarb. reenters cell, made back into CO2, etc.

b. CO2 released to air (low CO2 in alveloli/air pull CO2 off by Le Chatelier's principle higher CO2 conc. in blood than in alveoli)

c. O2 helps drive off CO2 and H + from Hb. (Additional push factor.)

Next Time: Gas Exchange, cont How is salt & water balance maintained?


Contents

The discovery of a natriuretic factor (one that promotes kidney excretion of salt and water) was first reported by de Bold in 1981 when rat atrial extracts were found to contain a substance that increased salt and urine output in the kidney. [3] Later, the substance was purified from heart tissue by several groups and named atrial natriuretic factor (ANF) or ANP. [4]

ANP is a 28-amino acid peptide with a 17-amino acid ring in the middle of the molecule. The ring is formed by a disulfide bond between two cysteine residues at positions 7 and 23. ANP is closely related to BNP (brain natriuretic peptide) and CNP (C-type natriuretic peptide), which all share a similar amino acid ring structure. ANP is one of a family of nine structurally similar natriuretic hormones: seven are atrial in origin. [5]

ANP is synthesized as an inactive preprohormone, encoded by the human NPPA gene located on the short arm of chromosome 1. [2] The NPPA gene is expressed primarily in atrial myocytes and consists of 2 introns and three exons, with translation of this gene yielding a high molecular mass 151 amino acid polypeptide known as preproANP. [6] The preprohormone is activated via post-translational modification that involves cleavage of the 25 amino acid signal sequence to produce proANP, a 126 amino acid peptide that is the major form of ANP stored in intracellular granules of the atria. [6] Following stimulation of atrial cells, proANP is released and rapidly converted to the 28-amino-acid C-terminal mature ANP on the cell surface by the cardiac transmembrane serine protease corin. [7] [8] Recently, it was discovered that ANP also can be O-glycosylated. [9]

ANP is secreted in response to:

  • Stretching of the atrial wall, via Atrial volume receptors
  • Increased Sympathetic stimulation of β-adrenoceptors
  • Increased sodium concentration (hypernatremia), though sodium concentration is not the direct stimulus for increased ANP secretion [10] , a potent vasoconstrictor

Three types of atrial natriuretic peptide receptors have been identified on which natriuretic peptides act. They are all cell surface receptors and designated:

  • guanylyl cyclase-A (GC-A) also known as natriuretic peptide receptor-A (NPRA/ANPA) or NPR1
  • guanylyl cyclase-B (GC-B) also known as natriuretic peptide receptor-B (NPRB/ANPB) or NPR2
  • natriuretic peptide clearance receptor (NPRC/ANPC) or NPR3

NPR-A and NPR-B have a single membrane-spanning segment with an extracellular domain that binds the ligand. [ citation needed ] The intracellular domain maintains two consensus catalytic domains for guanylyl cyclase activity. Binding of a natriuretic peptide induces a conformational change in the receptor that causes receptor dimerization and activation. [ citation needed ]

The binding of ANP to its receptor causes the conversion of GTP to cGMP and raises intracellular cGMP. As a consequence, cGMP activates a cGMP-dependent kinase (PKG or cGK) that phosphorylates proteins at specific serine and threonine residues. In the medullary collecting duct, the cGMP generated in response to ANP may act not only through PKG but also via direct modulation of ion channels. [11]

NPR-C functions mainly as a clearance receptor by binding and sequestering ANP from the circulation. All natriuretic peptides are bound by the NPR-C. [ citation needed ]

Maintenance of the ECF volume (space), and its subcompartment the vascular space, is crucial for survival. [ citation needed ] These compartments are maintained within a narrow range, despite wide variations in dietary sodium intake. There are three volume regulating systems: two salt saving systems, the renin angiotensin aldosterone system (RAAS) and the renal sympathetic system (RSS) and the salt excreting natriuretic peptide (NP) hormone system. When the vascular space contracts, the RAAS and RSS are "turned on" when the atria expand, NP's are "turned on". Each system also suppresses its counteracting system(s). NP's are made in cardiac, intestinal, renal, and adrenal tissue: ANP in one of a family of cardiac NP's: others at BNP, CNP, and DNP. [5]

ANP binds to a specific set of receptors – ANP receptors. Receptor-agonist binding causes the increase in renal sodium excretion, which results in a decreased ECF and blood volume. Secondary effects may be an improvement in cardiac ejection fraction and reduction of systemic blood pressure. [ citation needed ]

Renal Edit

ANP acts on the kidney to increase sodium and water excretion (natriuresis) in the following ways: [12] [13]

  • The medullary collecting duct is the main site of ANP regulation of sodium excretion. [14] ANP effects sodium channels at both the apical and basolateral sides. [14] ANP inhibits ENaC on the apical side and the Sodium Potassium ATPase pump on the basolateral side in a cGMP PKG dependent manner resulting in less sodium re-absorption and more sodium excretion. [15]
  • ANP increases glomerular filtration rate and glomerular permeability. [14] ANP directly dilates the afferent arteriole and counteracts the norepinephrine induced vasoconstriction of the afferent arteriole. [15] Some studies suggest that ANP also constricts the efferent arteriole, but this is not a unanimous finding. [15] ANP inhibits the effect of Angiotensin II on the mesangial cells, thereby relaxing them. [15] ANP increases the radius and number of glomerular pores, thereby increasing glomerular permeability and resulting in greater filter load of sodium and water. [14]
  • Increases blood flow through the vasa recta, which will wash the solutes (sodium chloride (NaCl), and urea) out of the medullary interstitium. The lower osmolarity of the medullary interstitium leads to less reabsorption of tubular fluid and increased excretion.
  • Decreases sodium reabsorption at least in the thick ascending limb (interaction with NKCC2) and cortical collecting duct of the nephron via guanosine 3',5'-cyclic monophosphate (cGMP) dependent phosphorylation of ENaC.
  • It inhibits renin secretion, thereby inhibiting the production of angiotensin and aldosterone.
  • It inhibits the renal sympathetic nervous system.

ANP has the opposite effect of angiotensin II on the kidney: angiotensin II increases renal sodium retention and ANP increases renal sodium loss.

Adrenal Edit

Vascular Edit

Relaxes vascular smooth muscle in arterioles and venules by:

  • Membrane Receptor-mediated elevation of vascular smooth muscle cGMP
  • Inhibition of the effects of catecholamines

Promotes uterine spiral artery remodeling, which is important for preventing pregnancy-induced hypertension. [16]

Cardiac Edit

  • ANP inhibits cardiac hypertrophy in heart failure as well as fibrosis. [17] Fibrosis is inhibited by preventing fibroblasts from entering heart tissue and replicating, as well as decreasing inflammation. [17] ANP prevents hypertrophy by inhibiting calcium influx that is caused by norepinephrine. [17]
  • Re-expression of NPRA rescues the phenotype. [citation needed]

Adipose tissue Edit

  • Increases the release of free fatty acids from adipose tissue. Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans.
  • Activates adipocyte plasma membrane type A guanylyl cyclase receptors NPR-A
  • Increases intracellular cGMP levels that induce the phosphorylation of a hormone-sensitive lipase and perilipin A via the activation of a cGMP-dependent protein kinase-I (cGK-I)
  • Does not modulate cAMP production or PKA activity.

Immune System Edit

ANP is produced locally by several immune cells. ANP is shown to regulate several functions of innate and adaptive immune system as well as shown to have cytoprotective effects. [18]

  • ANP modulates innate immunity by raising defence against extracellular microbes and inhibiting the release of pro-inflammatory markers and expression of adhesion molecules. [18]
  • There is evidence of cytoprotective effects of ANP in myocardial, vascular smooth, endothelial, hepatocytes and tumour cells. [18]

Modulation of the effects of ANP is achieved through gradual degradation of the peptide by the enzyme neutral endopeptidase (NEP). Recently, NEP inhibitors have been developed, such as Sacubitril and Sacubitril/valsartan. They may be clinically useful in treating patients in heart failure with reduced ejection fraction .

Fragments derived from the ANP precursor, including the signal peptide, N-terminal pro-ANP and ANP, have been detected in human blood. [19] ANP and related peptides are used as biomarkers for cardiovascular diseases such as stroke, coronary artery disease, myocardial infarction and heart failure. [20] [21] [22] [23] A specific ANP precursor called mid-regional pro-atrial natriuretic peptide (MRproANP) is a highly sensitive biomarker in heart failure. [24] MRproANP levels below 120 pmol/L can be used to effectively rule out acute heart failure. [24]

Large amounts of ANP secretion has been noted to cause electrolyte disturbances (hyponatremia) and polyuria. These indications can be a marker of a large atrial myxoma. [25]

Opinions regarding the use of ANP for the treatment of acute heart failure and kidney disease are varied. [26] While this molecule has been shown to successfully restore some hemodynamic parameters following heart failure, and yield clinical improvement for kidney injury, whether it ultimately reduces mortality and its long-term effects are unknown. [27] Therefore, more studies need to be conducted to better understand the therapeutic effects of ANP. [27] Newly synthesized homologues of ANP molecule are being assessed for the treatment of acute heart failure. [28] Preliminary research on one of such molecules, ularitide, has shown that this drug is safe, well tolerated, and effective in the treatment of acute heart failure. [28]

Brain natriuretic peptide (BNP) – a misnomer it is secreted by ventricular myocytes – is similar to ANP in its effect. It acts via atrial natriuretic peptide receptors but with 10-fold lower affinity than ANP. The biological half-life of BNP, however, is twice as long as that of ANP, and that of NT-proBNP is even longer, making these peptides better choices than ANP for diagnostic blood testing.

In addition to the mammalian natriuretic peptides (ANP, BNP, CNP), other natriuretic peptides with similar structure and properties have been isolated elsewhere in the animal kingdom. A salmon natriuretic peptide known as salmon cardiac peptide has been described, [29] and dendroaspis natriuretic peptide (DNP) has been found in the venom of the green mamba, as well as an NP in a species of African snake. [30]

Beside these four, five additional natriuretic peptides have been identified: long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide, urodilatin, and adrenomedullin. [5]

Neutral endopeptidase (NEP) also known as neprilysin is the enzyme that metabolizes natriuretic peptides. Several inhibitors of NEP are currently being developed to treat disorders ranging from hypertension to heart failure. Most of them are dual inhibitors (NEP and ACE). In 2014, PARADIGM-HF study was published in NEJM. This study considered as a landmark study in treatment of heart failure. The study was double blinded compared LCZ696 versus enalapril in patients with heart failure. The study showed lower all cause mortality, cardiovascular mortality and hospitalization in LCZ696 arm. [31] Omapatrilat (dual inhibitor of NEP and angiotensin-converting enzyme) developed by BMS did not receive FDA approval due to angioedema safety concerns. Other dual inhibitors of NEP with ACE/angiotensin receptor are (in 2003) being developed by pharmaceutical companies. [32]

ANP is also called atrial natriuretic factor (ANF), atrial natriuretic hormone (ANH), cardionatrine, cardiodilatin (CDD), and atriopeptin.


Disorders of the Heart: Abnormal Heart Rates

For an adult, normal resting HR will be in the range of 60–100 bpm. Bradycardia is the condition in which resting rate drops below 60 bpm, and tachycardia is the condition in which the resting rate is above 100 bpm. Trained athletes typically have very low HRs. If the patient is not exhibiting other symptoms, such as weakness, fatigue, dizziness, fainting, chest discomfort, palpitations, or respiratory distress, bradycardia is not considered clinically significant. However, if any of these symptoms are present, they may indicate that the heart is not providing sufficient oxygenated blood to the tissues. The term relative bradycardia may be used with a patient who has a HR in the normal range but is still suffering from these symptoms. Most patients remain asymptomatic if the HR remains above 50 bpm.

Bradycardia may be caused by either inherent factors or causes external to the heart. While the condition may be inherited, typically it is acquired in older individuals. Inherent causes include abnormalities in either the SA or AV node. If the condition is serious, a pacemaker may be required. Other causes include ischaemia to the heart muscle or diseases of the heart vessels or valves. External causes include metabolic disorders, pathologies of the endocrine system often involving the thyroid, electrolyte imbalances, neurological disorders including inappropriate autonomic responses, autoimmune pathologies, over-prescription of beta blocker drugs that reduce HR, recreational drug use, or even prolonged bed rest. Treatment relies upon establishing the underlying cause of the disorder and may necessitate supplemental oxygen.

Tachycardia is not normal in a resting patient but may be detected in pregnant women or individuals experiencing extreme stress. In the latter case, it would likely be triggered by stimulation from the limbic system or disorders of the autonomic nervous system. In some cases, tachycardia may involve only the atria. Some individuals may remain asymptomatic, but when present, symptoms may include dizziness, shortness of breath, light-headedness, rapid pulse, heart palpations, chest pain, or fainting (syncope). While tachycardia is defined as a HR above 100 bpm, there is considerable variation among people. Further, the normal resting HRs of children are often above 100 bpm, but this is not considered to be tachycardia Many causes of tachycardia may be benign, but the condition may also be correlated with fever, anaemia, hypoxia, hyperthyroidism, hypersecretion of catecholamines, some cardiomyopathies, some disorders of the valves, and acute exposure to radiation. Elevated rates in an exercising or resting patient are normal and expected. Resting rate should always be taken after recovery from exercise. Treatment depends upon the underlying cause but may include medications, implantable cardioverter defibrillators, ablation or surgery.


The heart functions as a pump and acts as a double pump in the cardiovascular system to provide a continuous circulation of blood throughout the body. This circulation includes the systemic circulation and the pulmonary circulation. Both circuits transport blood but they can also be seen in terms of the gases they carry. The pulmonary circulation collects oxygen from the lungs and delivers carbon dioxide for exhalation. The systemic circuit transports oxygen to the body and returns relatively de-oxygenated blood and carbon dioxide to the pulmonary circuit. [1]

Blood flows through the heart in one direction, from the atria to the ventricles, and out through the pulmonary artery into the pulmonary circulation, and the aorta into the systemic circulation. The pulmonary artery (also trunk) branches into the left and right pulmonary arteries to supply each lung. Blood is prevented from flowing backwards (regurgitation) by the tricuspid, bicuspid, aortic, and pulmonary valves.

The function of the right heart, is to collect de-oxygenated blood, in the right atrium, from the body via the superior vena cava, inferior vena cava and from the coronary sinus and pump it, through the tricuspid valve, via the right ventricle, through the semilunar pulmonary valve and into the pulmonary artery in the pulmonary circulation where carbon dioxide can be exchanged for oxygen in the lungs. This happens through the passive process of diffusion. In the left heart oxygenated blood is returned to the left atrium via the pulmonary vein. It is then pumped into the left ventricle through the bicuspid valve and into the aorta for systemic circulation. Eventually in the systemic capillaries exchange with the tissue fluid and cells of the body occurs oxygen and nutrients are supplied to the cells for their metabolism and exchanged for carbon dioxide and waste products [1] In this case, oxygen and nutrients exit the systemic capillaries to be used by the cells in their metabolic processes, and carbon dioxide and waste products will enter the blood. [1]

The ventricles are stronger and thicker than the atria, and the muscle wall surrounding the left ventricle is thicker than the wall surrounding the right ventricle due to the higher force needed to pump the blood through the systemic circulation. Atria facilitate circulation primarily by allowing uninterrupted venous flow to the heart, preventing the inertia of interrupted venous flow that would otherwise occur at each ventricular systole. [2]

Cardiac muscle tissue has autorhythmicity, the unique ability to initiate a cardiac action potential at a fixed rate – spreading the impulse rapidly from cell to cell to trigger the contraction of the entire heart. This autorhythmicity is still modulated by the endocrine and nervous systems. [1]

There are two types of cardiac muscle cell: cardiomyocytes which have the ability to contract easily, and modified cardiomyocytes the pacemaker cells of the conducting system. The cardiomyocytes make up the bulk (99%) of cells in the atria and ventricles. These contractile cells respond to impulses of action potential from the pacemaker cells and are responsible for the contractions that pump blood through the body. The pacemaker cells make up just (1% of cells) and form the conduction system of the heart. They are generally much smaller than the contractile cells and have few of the myofibrils or myofilaments which means that they have limited contractibility. Their function is similar in many respects to neurons. [1] The bundle of His and Purkinje fibres are specialised cardiomyocytes that function in the conduction system.

Structure of cardiac muscle Edit

Cardiomyocytes, are considerably shorter and have smaller diameters than skeletal myocytes. Cardiac muscle (like skeletal muscle) is characterized by striations – the stripes of dark and light bands resulting from the organised arrangement of myofilaments and myofibrils in the sarcomere along the length of the cell. T (transverse) tubules are deep invaginations from the sarcolemma (cell membrane) that penetrate the cell, allowing the electrical impulses to reach the interior. In cardiac muscle the T-tubules are only found at the Z-lines. [1] When an action potential causes cells to contract, calcium is released from the sarcoplasmic reticulum of the cells as well as the T tubules. The calcium release triggers sliding of the actin and myosin fibrils leading to contraction. [3] A plentiful supply of mitochondria provide the energy for the contractions. Typically, cardiomyocytes have a single, central nucleus, but can also have two or more. [1]

Cardiac muscle cells branch freely and are connected by junctions known as intercalated discs which help the synchronized contraction of the muscle. [4] The sarcolemma (membrane) from adjacent cells bind together at the intercalated discs. They consist of desmosomes, specialized linking proteoglycans, tight junctions, and large numbers of gap junctions that allow the passage of ions between the cells and help to synchronize the contraction. Intercellular connective tissue also helps to strongly bind the cells together, in order to withstand the forces of contraction. [1]

Cardiac muscle undergoes aerobic respiration patterns, primarily metabolizing lipids and carbohydrates. Oxygen from the lungs attaches to haemoglobin and is also stored in the myoglobin, so that a plentiful supply of oxygen is available. Lipids, and glycogen are also stored within the sarcoplasm and these are broken down by mitochondria to release ATP. The cells undergo twitch-type contractions with long refractory periods followed by brief relaxation periods when the heart fills with blood for the next cycle. [1]

It is not very well known how the electric signal moves in the atria. It seems that it moves in a radial way, but Bachmann's bundle and coronary sinus muscle play a role in conduction between the two atria, which have a nearly simultaneous systole. [5] [6] [7] While in the ventricles, the signal is carried by specialized tissue called the Purkinje fibers which then transmit the electric charge to the myocardium. [8]

If embryonic heart cells are separated into a Petri dish and kept alive, each is capable of generating its own electrical impulse followed by contraction. When two independently beating embryonic cardiac muscle cells are placed together, the cell with the higher inherent rate sets the pace, and the impulse spreads from the faster to the slower cell to trigger a contraction. As more cells are joined together, the fastest cell continues to assume control of the rate. A fully developed adult heart maintains the capability of generating its own electrical impulse, triggered by the fastest cells, as part of the cardiac conduction system. The components of the cardiac conduction system include the atrial and ventricular syncytium, the sinoatrial node, the atrioventricular node, the bundle of His (atrioventricular bundle), the bundle branches, and the Purkinje cells. [1]

Sinoatrial (SA) node Edit

Normal sinus rhythm is established by the sinoatrial (SA) node, the heart's pacemaker. The SA node is a specialized grouping of cardiomyocytes in the upper and back walls of the right atrium very close to the opening of the superior vena cava. The SA node has the highest rate of depolarization. [1]

This impulse spreads from its initiation in the SA node throughout the atria through specialized internodal pathways, to the atrial myocardial contractile cells and the atrioventricular node. The internodal pathways consist of three bands (anterior, middle, and posterior) that lead directly from the SA node to the next node in the conduction system, the atrioventricular node. The impulse takes approximately 50 ms (milliseconds) to travel between these two nodes. The relative importance of this pathway has been debated since the impulse would reach the atrioventricular node simply following the cell-by-cell pathway through the contractile cells of the myocardium in the atria. In addition, there is a specialized pathway called Bachmann's bundle or the interatrial band that conducts the impulse directly from the right atrium to the left atrium. Regardless of the pathway, as the impulse reaches the atrioventricular septum, the connective tissue of the cardiac skeleton prevents the impulse from spreading into the myocardial cells in the ventricles except at the atrioventricular node. [1] The electrical event, the wave of depolarization, is the trigger for muscular contraction. The wave of depolarization begins in the right atrium, and the impulse spreads across the superior portions of both atria and then down through the contractile cells. The contractile cells then begin contraction from the superior to the inferior portions of the atria, efficiently pumping blood into the ventricles. [1]

Atrioventricular (AV) node Edit

The atrioventricular (AV) node is a second cluster of specialized myocardial conductive cells, located in the inferior portion of the right atrium within the atrioventricular septum. The septum prevents the impulse from spreading directly to the ventricles without passing through the AV node. There is a critical pause before the AV node depolarizes and transmits the impulse to the atrioventricular bundle. This delay in transmission is partially attributable to the small diameter of the cells of the node, which slow the impulse. Also, conduction between nodal cells is less efficient than between conducting cells. These factors mean that it takes the impulse approximately 100 ms to pass through the node. This pause is critical to heart function, as it allows the atrial cardiomyocytes to complete their contraction that pumps blood into the ventricles before the impulse is transmitted to the cells of the ventricle itself. With extreme stimulation by the SA node, the AV node can transmit impulses maximally at 220 per minute. This establishes the typical maximum heart rate in a healthy young individual. Damaged hearts or those stimulated by drugs can contract at higher rates, but at these rates, the heart can no longer effectively pump blood. [1]

Bundle of His, bundle branches, and Purkinje fibers Edit

Arising from the AV node, the bundle of His, proceeds through the interventricular septum before dividing into two bundle branches, commonly called the left and right bundle branches. The left bundle branch has two fascicles. The left bundle branch supplies the left ventricle, and the right bundle branch the right ventricle. Since the left ventricle is much larger than the right, the left bundle branch is also considerably larger than the right. Portions of the right bundle branch are found in the moderator band and supply the right papillary muscles. Because of this connection, each papillary muscle receives the impulse at approximately the same time, so they begin to contract simultaneously just prior to the remainder of the myocardial contractile cells of the ventricles. This is believed to allow tension to develop on the chordae tendineae prior to right ventricular contraction. There is no corresponding moderator band on the left. Both bundle branches descend and reach the apex of the heart where they connect with the Purkinje fibers. This passage takes approximately 25 ms. [1]

The Purkinje fibers are additional myocardial conductive fibers that spread the impulse to the myocardial contractile cells in the ventricles. They extend throughout the myocardium from the apex of the heart toward the atrioventricular septum and the base of the heart. The Purkinje fibers have a fast inherent conduction rate, and the electrical impulse reaches all of the ventricular muscle cells in about 75 ms. Since the electrical stimulus begins at the apex, the contraction also begins at the apex and travels toward the base of the heart, similar to squeezing a tube of toothpaste from the bottom. This allows the blood to be pumped out of the ventricles and into the aorta and pulmonary trunk. The total time elapsed from the initiation of the impulse in the SA node until depolarization of the ventricles is approximately 225 ms. [1]

Membrane potentials and ion movement in cardiac conductive cells Edit

Action potentials are considerably different between conductive and contractive cardiomyocytes. While sodium Na + and potassium K + ions play essential roles, calcium ions Ca 2+ are also critical for both types of cell. Unlike skeletal muscles and neurons, cardiac conductive cells do not have a stable resting potential. Conductive cells contain a series of sodium ion channels that allow a normal and slow influx of sodium ions that causes the membrane potential to rise slowly from an initial value of −60 mV up to about –40 mV. The resulting movement of sodium ions creates spontaneous depolarization (or prepotential depolarization). [1]

At this point, calcium channels open and Ca 2+ enters the cell, further depolarizing it at a more rapid rate until it reaches a value of approximately +5 mV. At this point, the calcium ion channels close and potassium channels open, allowing outflux of K + and resulting in repolarization. When the membrane potential reaches approximately −60 mV, the K + channels close and Na + channels open, and the prepotential phase begins again. This process gives the autorhythmicity to cardiac muscle. [1]

Membrane Potentials and ion movement in cardiac contractile cells Edit

There is a distinctly different electrical pattern involving the contractile cells. In this case, there is a rapid depolarization, followed by a plateau phase and then repolarization. This phenomenon accounts for the long refractory periods required for the cardiac muscle cells to pump blood effectively before they are capable of firing for a second time. These cardiac myocytes normally do not initiate their own electrical potential, although they are capable of doing so, but rather wait for an impulse to reach them. [1]

Contractile cells demonstrate a much more stable resting phase than conductive cells at approximately −80 mV for cells in the atria and −90 mV for cells in the ventricles. Despite this initial difference, the other components of their action potentials are virtually identical. In both cases, when stimulated by an action potential, voltage-gated channels rapidly open, beginning the positive-feedback mechanism of depolarization. This rapid influx of positively charged ions raises the membrane potential to approximately +30 mV, at which point the sodium channels close. The rapid depolarization period typically lasts 3–5 ms. Depolarization is followed by the plateau phase, in which membrane potential declines relatively slowly. This is due in large part to the opening of the slow Ca 2+ channels, allowing Ca 2+ to enter the cell while few K + channels are open, allowing K + to exit the cell. The relatively long plateau phase lasts approximately 175 ms. Once the membrane potential reaches approximately zero, the Ca 2+ channels close and K + channels open, allowing K + to exit the cell. The repolarization lasts approximately 75 ms. At this point, membrane potential drops until it reaches resting levels once more and the cycle repeats. The entire event lasts between 250 and 300 ms. [1]

The absolute refractory period for cardiac contractile muscle lasts approximately 200 ms, and the relative refractory period lasts approximately 50 ms, for a total of 250 ms. This extended period is critical, since the heart muscle must contract to pump blood effectively and the contraction must follow the electrical events. Without extended refractory periods, premature contractions would occur in the heart and would not be compatible with life. [1]

Calcium ions Edit

Calcium ions play two critical roles in the physiology of cardiac muscle. Their influx through slow calcium channels accounts for the prolonged plateau phase and absolute refractory period. Calcium ions also combine with the regulatory protein troponin in the troponin complex. Both roles enabling the myocardium to function properly. [1]

Approximately 20 percent of the calcium required for contraction is supplied by the influx of Ca 2+ during the plateau phase. The remaining Ca 2+ for contraction is released from storage in the sarcoplasmic reticulum. [1]

Comparative rates of conduction system firing Edit

The pattern of prepotential or spontaneous depolarization, followed by rapid depolarization and repolarization just described, are seen in the SA node and a few other conductive cells in the heart. Since the SA node is the pacemaker, it reaches threshold faster than any other component of the conduction system. It will initiate the impulses spreading to the other conducting cells. The SA node, without nervous or endocrine control, would initiate a heart impulse approximately 80–100 times per minute. Although each component of the conduction system is capable of generating its own impulse, the rate progressively slows from the SA node to the Purkinje fibers. Without the SA node, the AV node would generate a heart rate of 40–60 beats per minute. If the AV node were blocked, the atrioventricular bundle would fire at a rate of approximately 30–40 impulses per minute. The bundle branches would have an inherent rate of 20–30 impulses per minute, and the Purkinje fibers would fire at 15–20 impulses per minute. While a few exceptionally trained aerobic athletes demonstrate resting heart rates in the range of 30–40 beats per minute (the lowest recorded figure is 28 beats per minute for Miguel Indurain, a cyclist)–for most individuals, rates lower than 50 beats per minute would indicate a condition called bradycardia. Depending upon the specific individual, as rates fall much below this level, the heart would be unable to maintain adequate flow of blood to vital tissues, initially resulting in decreasing loss of function across the systems, unconsciousness, and ultimately death. [1]

The period of time that begins with contraction of the atria and ends with ventricular relaxation is known as the cardiac cycle. The period of contraction that the heart undergoes while it pumps blood into circulation is called systole. The period of relaxation that occurs as the chambers fill with blood is called diastole. Both the atria and ventricles undergo systole and diastole, and it is essential that these components be carefully regulated and coordinated to ensure blood is pumped efficiently to the body. [1]

Pressures and flow Edit

Fluids, move from regions of high pressure to regions of lower pressure. Accordingly, when the heart chambers are relaxed (diastole), blood will flow into the atria from the higher pressure of the veins. As blood flows into the atria, the pressure will rise, so the blood will initially move passively from the atria into the ventricles. When the action potential triggers the muscles in the atria to contract (atrial systole), the pressure within the atria rises further, pumping blood into the ventricles. During ventricular systole, pressure rises in the ventricles, pumping blood into the pulmonary trunk from the right ventricle and into the aorta from the left ventricle. [1]

Phases of the cardiac cycle Edit

At the beginning of the cardiac cycle, both the atria and ventricles are relaxed (diastole). Blood is flowing into the right atrium from the superior and inferior venae cavae and the coronary sinus. Blood flows into the left atrium from the four pulmonary veins. The two atrioventricular valves, the tricuspid and mitral valves, are both open, so blood flows unimpeded from the atria and into the ventricles. Approximately 70–80 percent of ventricular filling occurs by this method. The two semilunar valves, the pulmonary and aortic valves, are closed, preventing backflow of blood into the right and left ventricles from the pulmonary trunk on the right and the aorta on the left. [1]

Atrial systole and diastole Edit

Contraction of the atria follows depolarization, represented by the P wave of the ECG. As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum, pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular (tricuspid, and mitral or bicuspid) valves. At the start of atrial systole, the ventricles are normally filled with approximately 70–80 percent of their capacity due to inflow during diastole. Atrial contraction, also referred to as the "atrial kick," contributes the remaining 20–30 percent of filling. Atrial systole lasts approximately 100 ms and ends prior to ventricular systole, as the atrial muscle returns to diastole. [1]

Ventricular systole Edit

Ventricular systole follows the depolarization of the ventricles and is represented by the QRS complex in the ECG. It may be conveniently divided into two phases, lasting a total of 270 ms. At the end of atrial systole and just prior to ventricular contraction, the ventricles contain approximately 130 mL blood in a resting adult in a standing position. This volume is known as the end diastolic volume (EDV) or preload. [1]

Initially, as the muscles in the ventricle contract, the pressure of the blood within the chamber rises, but it is not yet high enough to open the semilunar (pulmonary and aortic) valves and be ejected from the heart. However, blood pressure quickly rises above that of the atria that are now relaxed and in diastole. This increase in pressure causes blood to flow back toward the atria, closing the tricuspid and mitral valves. Since blood is not being ejected from the ventricles at this early stage, the volume of blood within the chamber remains constant. Consequently, this initial phase of ventricular systole is known as isovolumic contraction, also called isovolumetric contraction. [1]

In the second phase of ventricular systole, the ventricular ejection phase, the contraction of the ventricular muscle has raised the pressure within the ventricle to the point that it is greater than the pressures in the pulmonary trunk and the aorta. Blood is pumped from the heart, pushing open the pulmonary and aortic semilunar valves. Pressure generated by the left ventricle will be appreciably greater than the pressure generated by the right ventricle, since the existing pressure in the aorta will be so much higher. Nevertheless, both ventricles pump the same amount of blood. This quantity is referred to as stroke volume. Stroke volume will normally be in the range of 70–80 mL. Since ventricular systole began with an EDV of approximately 130 mL of blood, this means that there is still 50–60 mL of blood remaining in the ventricle following contraction. This volume of blood is known as the end systolic volume (ESV). [1]

Ventricular diastole Edit

Ventricular relaxation, or diastole, follows repolarization of the ventricles and is represented by the T wave of the ECG. It too is divided into two distinct phases and lasts approximately 430 ms. [1]

During the early phase of ventricular diastole, as the ventricular muscle relaxes, pressure on the remaining blood within the ventricle begins to fall. When pressure within the ventricles drops below pressure in both the pulmonary trunk and aorta, blood flows back toward the heart, producing the dicrotic notch (small dip) seen in blood pressure tracings. The semilunar valves close to prevent backflow into the heart. Since the atrioventricular valves remain closed at this point, there is no change in the volume of blood in the ventricle, so the early phase of ventricular diastole is called the isovolumic ventricular relaxation phase, also called isovolumetric ventricular relaxation phase. [1]

In the second phase of ventricular diastole, called late ventricular diastole, as the ventricular muscle relaxes, pressure on the blood within the ventricles drops even further. Eventually, it drops below the pressure in the atria. When this occurs, blood flows from the atria into the ventricles, pushing open the tricuspid and mitral valves. As pressure drops within the ventricles, blood flows from the major veins into the relaxed atria and from there into the ventricles. Both chambers are in diastole, the atrioventricular valves are open, and the semilunar valves remain closed. The cardiac cycle is complete. [1]

One of the simplest methods of assessing the heart's condition is to listen to it using a stethoscope. [1] In a healthy heart, there are only two audible heart sounds, called S1 and S2. The first heart sound S1, is the sound created by the closing of the atrioventricular valves during ventricular contraction and is normally described as "lub". The second heart sound, S2, is the sound of the semilunar valves closing during ventricular diastole and is described as "dub". [1] Each sound consists of two components, reflecting the slight difference in time as the two valves close. [9] S2 may split into two distinct sounds, either as a result of inspiration or different valvular or cardiac problems. [9] Additional heart sounds may also be present and these give rise to gallop rhythms. A third heart sound, S3 usually indicates an increase in ventricular blood volume. A fourth heart sound S4 is referred to as an atrial gallop and is produced by the sound of blood being forced into a stiff ventricle. The combined presence of S3 and S4 give a quadruple gallop. [1]

Heart murmurs are abnormal heart sounds which can be either pathological or benign and there are numerous kinds. [10] Murmurs are graded by volume, from 1) the quietest, to 6) the loudest, and evaluated by their relationship to the heart sounds and position in the cardiac cycle. [9] Phonocardiograms can record these sounds. [1] Murmurs can result from narrowing (stenosis), regurgitation or insufficiency of any of the main heart valves but they can also result from a number of other disorders, including atrial and ventricular septal defects. [9] One example of a murmur is Still's murmur, which presents a musical sound in children, has no symptoms and disappears in adolescence. [11]

A different type of sound, a pericardial friction rub can be heard in cases of pericarditis where the inflamed membranes can rub together. [12]

The resting heart rate of a newborn can be 120 beats per minute (bpm) and this gradually decreases until maturity and then gradually increases again with age. The adult resting heart rate ranges from 60–100 bpm. Exercise and fitness levels, age and basal metabolic rate can all affect the heart rate. An athlete's heart rate can be lower than 60 bpm. During exercise the rate can be 150 bpm with maximum rates reaching from 200 and 220 bpm. [1]

Cardiovascular centres Edit

The normal sinus rhythm of the heart rate is generated by the SA node. It is also influenced by central factors through sympathetic and parasympathetic nerves [3] : 116–22 of the two paired cardiovascular centres of the medulla oblongata. Activity is increased via sympathetic stimulation of the cardioaccelerator nerves, and inhibited via parasympathetic stimulation by the vagus nerve. During rest vagal stimulation normally predominates as, left unregulated, the SA node would initiate a sinus rhythm of approximately 100 bpm. [1]

Both sympathetic and parasympathetic stimuli flow through the paired cardiac plexus near the base of the heart. Without any nervous stimulation, the SA node would establish a sinus rhythm of approximately 100 bpm. Since resting rates are considerably less than this, it becomes evident that parasympathetic stimulation normally slows HR. [1] The cardioaccelerator center also sends additional fibers, forming the cardiac nerves via sympathetic ganglia (the cervical ganglia plus superior thoracic ganglia T1–T4) to both the SA and AV nodes, plus additional fibers to the atria and ventricles. The ventricles are more richly innervated by sympathetic fibers than parasympathetic fibers. Sympathetic stimulation causes the release of the neurotransmitter norepinephrine (also known as noradrenaline) at the neuromuscular junction of the cardiac nerves. This shortens the repolarization period, thus speeding the rate of depolarization and contraction, which results in an increased heartrate. It opens chemical or ligand-gated sodium and calcium ion channels, allowing an influx of positively charged ions. [1] Norepinephrine binds to the beta–1 receptor. High blood pressure medications are used to block these receptors and so reduce the heart rate. [1]

The cardiovascular centres receive input from a series of visceral receptors with impulses traveling through visceral sensory fibers within the vagus and sympathetic nerves via the cardiac plexus. Among these receptors are various proprioreceptors, baroreceptors, and chemoreceptors, plus stimuli from the limbic system which normally enable the precise regulation of heart function, via cardiac reflexes. Increased physical activity results in increased rates of firing by various proprioreceptors located in muscles, joint capsules, and tendons. The cardiovascular centres monitor these increased rates of firing, suppressing parasympathetic stimulation or increasing sympathetic stimulation as needed in order to increase blood flow. [1]

Similarly, baroreceptors are stretch receptors located in the aortic sinus, carotid bodies, the venae cavae, and other locations, including pulmonary vessels and the right side of the heart itself. Rates of firing from the baroreceptors represent blood pressure, level of physical activity, and the relative distribution of blood. The cardiac centers monitor baroreceptor firing to maintain cardiac homeostasis, a mechanism called the baroreceptor reflex. With increased pressure and stretch, the rate of baroreceptor firing increases, and the cardiac centers decrease sympathetic stimulation and increase parasympathetic stimulation. As pressure and stretch decrease, the rate of baroreceptor firing decreases, and the cardiac centers increase sympathetic stimulation and decrease parasympathetic stimulation. [1]

There is a similar reflex, called the atrial reflex or Bainbridge reflex, associated with varying rates of blood flow to the atria. Increased venous return stretches the walls of the atria where specialized baroreceptors are located. However, as the atrial baroreceptors increase their rate of firing and as they stretch due to the increased blood pressure, the cardiac center responds by increasing sympathetic stimulation and inhibiting parasympathetic stimulation to increase HR. The opposite is also true. [1]

Factors influencing heart rate Edit

In addition to the autonomic nervous system, other factors can affect this. These include epinephrine, norepinephrine, and thyroid hormones levels of various ions including calcium, potassium, and sodium body temperature hypoxia and pH balance . [1]

Factors that increase heart rate also trigger an increase in stroke volume. As with skeletal muscles the heart can increase in size and efficiency with exercise. [1] Thus endurance athletes such as marathon runners may have a heart that has hypertrophied by up to 40%. [3] : 1063–64 The difference between maximum and minimum cardiac outputs is known as the cardiac reserve and this measures the residual capacity to pump blood. [1] Heart rates may reach up to 185–195 in exercise, depending on how fit a person is. [3]

Cardiac output (CO) is a measurement of the amount of blood pumped by each ventricle (stroke volume, SV) in one minute. To calculate this, multiply stroke volume (SV), by heart rate (HR), in beats per minute. [1] It can be represented by the equation: CO = HR x SV [1]

SV is normally measured using an echocardiogram to record end diastolic volume (EDV) and end systolic volume (ESV), and calculating the difference: SV = EDV – ESV. SV can also be measured using a specialized catheter, but this is an invasive procedure and far more dangerous to the patient. A mean SV for a resting 70-kg (150-lb) individual would be approximately 70 mL. There are several important variables, including size of the heart, physical and mental condition of the individual, sex, contractility, duration of contraction, preload or EDV, and afterload or resistance. Normal range for SV would be 55–100 mL. An average resting HR would be approximately 75 bpm but could range from 60–100 in some individuals. [1] Using these numbers, (which refer to each ventricle, not both) the mean CO is 5.25 L/min, with a range of 4.0–8.0 L/min. [1]

SVs are also used to calculate ejection fraction, which is the portion of the blood that is pumped or ejected from the heart with each contraction. To calculate ejection fraction, SV is divided by EDV. Despite the name, the ejection fraction is normally expressed as a percentage. Ejection fractions range from approximately 55–70 percent, with a mean of 58 percent. [1]


5.4: Cardiac Cycle - Biology

2. End-of-chapter questions

1 Where is the mammalian heart beat initiated?

A atrioventricular node
B left atrium
C Purkyne tissue
D sinoatrial node

2 What causes the bicuspid valve to close during ventricular systole?

A a greater blood pressure in the left atrium than in the left ventricle
B a greater blood pressure in the left ventricle than in the left atrium
C contraction of muscles in the septum
D contraction of muscles in the valve

3 Figure below shows the pressure changes in the left atrium, left ventricle and aorta throughout two cardiac cycles. Make a copy of this diagram.

a i How long does one heart beat (one cardiac cycle) last?
ii What is the heart rate represented on this graph, in beats per minute?
b The contraction of muscles in the ventricle wall causes the pressure inside the ventricle to rise. When the muscles relax, the pressure drops again. On your copy of the diagram, mark the following periods:
i the time when the ventricle is contracting (ventricular systole)
ii the time when the ventricle is relaxing (ventricular diastole).

c The contraction of muscles in the wall of the atrium raises the pressure inside it. This pressure is also raised when blood flows into the atrium from the veins, while the atrial walls are relaxed. On your copy of the diagram, mark the following periods:
i the time when the atrium is contracting (atrial systole)
ii the time when the atrium is relaxing (atrial diastole).

d The atrioventricular valves open when the pressure of the blood in the atria is greater than that in the ventricles. They snap shut when the pressure of the blood in the ventricles is greater than that in the atria. On your diagram,mark the point at which these valves will open and close.
e The opening and closing of the semilunar valves in the aorta depends in a similar way on the relative pressures inthe aorta and ventricles. On your diagram, mark the point at which these valves will open and close.
f The right ventricle has much less muscle in its walls than the left ventricle, and only develops about one-quarter of the pressure developed on the left side of the heart. On your diagram, draw a line to represent the probablepressure inside the right ventricle over the 1.3 seconds shown.

The diagram shows a normal ECG. The paper on which the ECG was recorded was running at a speed of 25 mm s -1



Heart Beat

The atria and ventricles work together, alternately contracting and relaxing to pump blood through your heart. The electrical system of your heart is the power source that makes this possible.

Your heartbeat is triggered by electrical impulses that travel down a special pathway through your heart:

  1. SA node (sinoatrial node) – known as the heart’s natural pacemaker. The impulse starts in a small bundle of specialized cells located in the right atrium, called the SA node. The electrical activity spreads through the walls of the atria and causes them to contract. This forces blood into the ventricles. The SA node sets the rate and rhythm of your heartbeat. Normal heart rhythm is often called normal sinus rhythm because the SA (sinus) node fires regularly.
  2. AV node (atrioventricular node). The AV node is a cluster of cells in the center of the heart between the atria and ventricles, and acts like a gate that slows the electrical signal before it enters the ventricles. This delay gives the atria time to contract before the ventricles do.
  3. His-Purkinje Network. This pathway of fibers sends the impulse to the muscular walls of the ventricles and causes them to contract. This forces blood out of the heart to the lungs and body.
  4. The SA node fires another impulse and the cycle begins again.

At rest, a normal heart beats around 50 to 99 times a minute. Exercise, emotions, fever and some medications can cause your heart to beat faster, sometimes to well over 100 beats per minute.

How fast does the normal heart beat?

How fast the heart beats depends on the body's need for oxygen-rich blood. At rest, the SA node causes your heart to beat about 50 to 100 times each minute. During activity or excitement, your body needs more oxygen-rich blood the heart rate rises to well over 100 beats per minute.

Medications and some medical conditions may affect how fast your heart-rate is at rest and with exercise.

How do you know how fast your heart is beating?

You can tell how fast your heart is beating (your heart rate) by feeling your pulse. Your heart-rate is the amount of times your heart beats in one minute.

You will need a watch with a second hand.

Place your index and middle finger of your hand on the inner wrist of the other arm, just below the base of the thumb.

You should feel a tapping or pulsing against your fingers.

Count the number of taps you feel in 10 seconds.

Multiply that number by 6 to find out your heart-rate for one minute:

Pulse in 10 seconds x 6 = __ beats per minute (your heart-rate)

When feeling your pulse, you can also tell if your heart rhythm is regular or not.

Normal Heart Beat

1. The SA node sets the rate and rhythm of your heartbeat.

2. The SA node fires an impulse. The impulse spreads through the walls of the right and left atria, causing them to contract. This forces blood into the ventricles.

3. The impulse travels to the AV node. Here, the impulse slows for a moment before going on to the ventricles.

4. The impulse travels through a pathway of fibers called the HIS-Purkinje network. This network sends the impulse into the ventricles and causes them to contract. This forces blood out of the heart to the lungs and body.

5. The SA node fires another impulse. The cycle begins again.


Contents

Location and shape

The human heart is situated in the middle mediastinum, at the level of thoracic vertebrae T5-T8. A double-membraned sac called the pericardium surrounds the heart and attaches to the mediastinum. [15] The back surface of the heart lies near the vertebral column, and the front surface sits behind the sternum and rib cartilages. [7] The upper part of the heart is the attachment point for several large blood vessels—the venae cavae, aorta and pulmonary trunk. The upper part of the heart is located at the level of the third costal cartilage. [7] The lower tip of the heart, the apex, lies to the left of the sternum (8 to 9 cm from the midsternal line) between the junction of the fourth and fifth ribs near their articulation with the costal cartilages. [7]

The largest part of the heart is usually slightly offset to the left side of the chest (though occasionally it may be offset to the right) and is felt to be on the left because the left heart is stronger and larger, since it pumps to all body parts. Because the heart is between the lungs, the left lung is smaller than the right lung and has a cardiac notch in its border to accommodate the heart. [7] The heart is cone-shaped, with its base positioned upwards and tapering down to the apex. [7] An adult heart has a mass of 250–350 grams (9–12 oz). [16] The heart is often described as the size of a fist: 12 cm (5 in) in length, 8 cm (3.5 in) wide, and 6 cm (2.5 in) in thickness, [7] although this description is disputed, as the heart is likely to be slightly larger. [17] Well-trained athletes can have much larger hearts due to the effects of exercise on the heart muscle, similar to the response of skeletal muscle. [7]

Chambers

The heart has four chambers, two upper atria, the receiving chambers, and two lower ventricles, the discharging chambers. The atria open into the ventricles via the atrioventricular valves, present in the atrioventricular septum. This distinction is visible also on the surface of the heart as the coronary sulcus. [18] There is an ear-shaped structure in the upper right atrium called the right atrial appendage, or auricle, and another in the upper left atrium, the left atrial appendage. [19] The right atrium and the right ventricle together are sometimes referred to as the right heart. Similarly, the left atrium and the left ventricle together are sometimes referred to as the left heart. [6] The ventricles are separated from each other by the interventricular septum, visible on the surface of the heart as the anterior longitudinal sulcus and the posterior interventricular sulcus. [18]

The cardiac skeleton is made of dense connective tissue and this gives structure to the heart. It forms the atrioventricular septum which separates the atria from the ventricles, and the fibrous rings which serve as bases for the four heart valves. [20] The cardiac skeleton also provides an important boundary in the heart's electrical conduction system since collagen cannot conduct electricity. The interatrial septum separates the atria and the interventricular septum separates the ventricles. [7] The interventricular septum is much thicker than the interatrial septum, since the ventricles need to generate greater pressure when they contract. [7]

Valves

The heart has four valves, which separate its chambers. One valve lies between each atrium and ventricle, and one valve rests at the exit of each ventricle. [7]

The valves between the atria and ventricles are called the atrioventricular valves. Between the right atrium and the right ventricle is the tricuspid valve. The tricuspid valve has three cusps, [21] which connect to chordae tendinae and three papillary muscles named the anterior, posterior, and septal muscles, after their relative positions. [21] The mitral valve lies between the left atrium and left ventricle. It is also known as the bicuspid valve due to its having two cusps, an anterior and a posterior cusp. These cusps are also attached via chordae tendinae to two papillary muscles projecting from the ventricular wall. [22]

The papillary muscles extend from the walls of the heart to valves by cartilaginous connections called chordae tendinae. These muscles prevent the valves from falling too far back when they close. [23] During the relaxation phase of the cardiac cycle, the papillary muscles are also relaxed and the tension on the chordae tendineae is slight. As the heart chambers contract, so do the papillary muscles. This creates tension on the chordae tendineae, helping to hold the cusps of the atrioventricular valves in place and preventing them from being blown back into the atria. [7] [g] [21]

Two additional semilunar valves sit at the exit of each of the ventricles. The pulmonary valve is located at the base of the pulmonary artery. This has three cusps which are not attached to any papillary muscles. When the ventricle relaxes blood flows back into the ventricle from the artery and this flow of blood fills the pocket-like valve, pressing against the cusps which close to seal the valve. The semilunar aortic valve is at the base of the aorta and also is not attached to papillary muscles. This too has three cusps which close with the pressure of the blood flowing back from the aorta. [7]

Right heart

The right heart consists of two chambers, the right atrium and the right ventricle, separated by a valve, the tricuspid valve. [7]

The right atrium receives blood almost continuously from the body's two major veins, the superior and inferior venae cavae. A small amount of blood from the coronary circulation also drains into the right atrium via the coronary sinus, which is immediately above and to the middle of the opening of the inferior vena cava. [7] In the wall of the right atrium is an oval-shaped depression known as the fossa ovalis, which is a remnant of an opening in the fetal heart known as the foramen ovale. [7] Most of the internal surface of the right atrium is smooth, the depression of the fossa ovalis is medial, and the anterior surface has prominent ridges of pectinate muscles, which are also present in the right atrial appendage. [7]

The right atrium is connected to the right ventricle by the tricuspid valve. [7] The walls of the right ventricle are lined with trabeculae carneae, ridges of cardiac muscle covered by endocardium. In addition to these muscular ridges, a band of cardiac muscle, also covered by endocardium, known as the moderator band reinforces the thin walls of the right ventricle and plays a crucial role in cardiac conduction. It arises from the lower part of the interventricular septum and crosses the interior space of the right ventricle to connect with the inferior papillary muscle. [7] The right ventricle tapers into the pulmonary trunk, into which it ejects blood when contracting. The pulmonary trunk branches into the left and right pulmonary arteries that carry the blood to each lung. The pulmonary valve lies between the right heart and the pulmonary trunk. [7]

Left heart

The left heart has two chambers: the left atrium and the left ventricle, separated by the mitral valve. [7]

The left atrium receives oxygenated blood back from the lungs via one of the four pulmonary veins. The left atrium has an outpouching called the left atrial appendage. Like the right atrium, the left atrium is lined by pectinate muscles. [24] The left atrium is connected to the left ventricle by the mitral valve. [7]

The left ventricle is much thicker as compared with the right, due to the greater force needed to pump blood to the entire body. Like the right ventricle, the left also has trabeculae carneae, but there is no moderator band. The left ventricle pumps blood to the body through the aortic valve and into the aorta. Two small openings above the aortic valve carry blood to the heart itself, the left main coronary artery and the right coronary artery. [7]

Heart wall

The heart wall is made up of three layers: the inner endocardium, middle myocardium and outer epicardium. These are surrounded by a double-membraned sac called the pericardium.

The innermost layer of the heart is called the endocardium. It is made up of a lining of simple squamous epithelium and covers heart chambers and valves. It is continuous with the endothelium of the veins and arteries of the heart, and is joined to the myocardium with a thin layer of connective tissue. [7] The endocardium, by secreting endothelins, may also play a role in regulating the contraction of the myocardium. [7]

The middle layer of the heart wall is the myocardium, which is the cardiac muscle—a layer of involuntary striated muscle tissue surrounded by a framework of collagen. The cardiac muscle pattern is elegant and complex, as the muscle cells swirl and spiral around the chambers of the heart, with the outer muscles forming a figure 8 pattern around the atria and around the bases of the great vessels and the inner muscles, forming a figure 8 around the two ventricles and proceeding toward the apex. This complex swirling pattern allows the heart to pump blood more effectively. [7]

There are two types of cells in cardiac muscle: muscle cells which have the ability to contract easily, and pacemaker cells of the conducting system. The muscle cells make up the bulk (99%) of cells in the atria and ventricles. These contractile cells are connected by intercalated discs which allow a rapid response to impulses of action potential from the pacemaker cells. The intercalated discs allow the cells to act as a syncytium and enable the contractions that pump blood through the heart and into the major arteries. [7] The pacemaker cells make up 1% of cells and form the conduction system of the heart. They are generally much smaller than the contractile cells and have few myofibrils which gives them limited contractibility. Their function is similar in many respects to neurons. [7] Cardiac muscle tissue has autorhythmicity, the unique ability to initiate a cardiac action potential at a fixed rate—spreading the impulse rapidly from cell to cell to trigger the contraction of the entire heart. [7]

There are specific proteins expressed in cardiac muscle cells. [25] [26] These are mostly associated with muscle contraction, and bind with actin, myosin, tropomyosin, and troponin. They include MYH6, ACTC1, TNNI3, CDH2 and PKP2. Other proteins expressed are MYH7 and LDB3 that are also expressed in skeletal muscle. [27]

Pericardium

The pericardium is the sac that surrounds the heart. The tough outer surface of the pericardium is called the fibrous membrane. This is lined by a double inner membrane called the serous membrane that produces pericardial fluid to lubricate the surface of the heart. [28] The part of the serous membrane attached to the fibrous membrane is called the parietal pericardium, while the part of the serous membrane attached to the heart is known as the visceral pericardium. The pericardium is present in order to lubricate its movement against other structures within the chest, to keep the heart's position stabilised within the chest, and to protect the heart from infection. [29]

Coronary circulation

Heart tissue, like all cells in the body, needs to be supplied with oxygen, nutrients and a way of removing metabolic wastes. This is achieved by the coronary circulation, which includes arteries, veins, and lymphatic vessels. Blood flow through the coronary vessels occurs in peaks and troughs relating to the heart muscle's relaxation or contraction. [7]

Heart tissue receives blood from two arteries which arise just above the aortic valve. These are the left main coronary artery and the right coronary artery. The left main coronary artery splits shortly after leaving the aorta into two vessels, the left anterior descending and the left circumflex artery. The left anterior descending artery supplies heart tissue and the front, outer side, and the septum of the left ventricle. It does this by branching into smaller arteries—diagonal and septal branches. The left circumflex supplies the back and underneath of the left ventricle. The right coronary artery supplies the right atrium, right ventricle, and lower posterior sections of the left ventricle. The right coronary artery also supplies blood to the atrioventricular node (in about 90% of people) and the sinoatrial node (in about 60% of people). The right coronary artery runs in a groove at the back of the heart and the left anterior descending artery runs in a groove at the front. There is significant variation between people in the anatomy of the arteries that supply the heart [30] The arteries divide at their furthest reaches into smaller branches that join together at the edges of each arterial distribution. [7]

The coronary sinus is a large vein that drains into the right atrium, and receives most of the venous drainage of the heart. It receives blood from the great cardiac vein (receiving the left atrium and both ventricles), the posterior cardiac vein (draining the back of the left ventricle), the middle cardiac vein (draining the bottom of the left and right ventricles), and small cardiac veins. [31] The anterior cardiac veins drain the front of the right ventricle and drain directly into the right atrium. [7]

Small lymphatic networks called plexuses exist beneath each of the three layers of the heart. These networks collect into a main left and a main right trunk, which travel up the groove between the ventricles that exists on the heart's surface, receiving smaller vessels as they travel up. These vessels then travel into the atrioventricular groove, and receive a third vessel which drains the section of the left ventricle sitting on the diaphragm. The left vessel joins with this third vessel, and travels along the pulmonary artery and left atrium, ending in the inferior tracheobronchial node. The right vessel travels along the right atrium and the part of the right ventricle sitting on the diaphragm. It usually then travels in front of the ascending aorta and then ends in a brachiocephalic node. [32]

Nerve supply

The heart receives nerve signals from the vagus nerve and from nerves arising from the sympathetic trunk. These nerves act to influence, but not control, the heart rate. Sympathetic nerves also influence the force of heart contraction. [33] Signals that travel along these nerves arise from two paired cardiovascular centres in the medulla oblongata. The vagus nerve of the parasympathetic nervous system acts to decrease the heart rate, and nerves from the sympathetic trunk act to increase the heart rate. [7] These nerves form a network of nerves that lies over the heart called the cardiac plexus. [7] [32]

The vagus nerve is a long, wandering nerve that emerges from the brainstem and provides parasympathetic stimulation to a large number of organs in the thorax and abdomen, including the heart. [34] The nerves from the sympathetic trunk emerge through the T1-T4 thoracic ganglia and travel to both the sinoatrial and atrioventricular nodes, as well as to the atria and ventricles. The ventricles are more richly innervated by sympathetic fibers than parasympathetic fibers. Sympathetic stimulation causes the release of the neurotransmitter norepinephrine (also known as noradrenaline) at the neuromuscular junction of the cardiac nerves. This shortens the repolarization period, thus speeding the rate of depolarization and contraction, which results in an increased heart rate. It opens chemical or ligand-gated sodium and calcium ion channels, allowing an influx of positively charged ions. [7] Norepinephrine binds to the beta–1 receptor. [7]

The heart is the first functional organ to develop and starts to beat and pump blood at about three weeks into embryogenesis. This early start is crucial for subsequent embryonic and prenatal development.

The heart derives from splanchnopleuric mesenchyme in the neural plate which forms the cardiogenic region. Two endocardial tubes form here that fuse to form a primitive heart tube known as the tubular heart. [35] Between the third and fourth week, the heart tube lengthens, and begins to fold to form an S-shape within the pericardium. This places the chambers and major vessels into the correct alignment for the developed heart. Further development will include the septa and valves formation and remodelling of the heart chambers. By the end of the fifth week the septa are complete and the heart valves are completed by the ninth week. [7]

Before the fifth week, there is an opening in the fetal heart known as the foramen ovale. The foramen ovale allowed blood in the fetal heart to pass directly from the right atrium to the left atrium, allowing some blood to bypass the lungs. Within seconds after birth, a flap of tissue known as the septum primum that previously acted as a valve closes the foramen ovale and establishes the typical cardiac circulation pattern. A depression in the surface of the right atrium remains where the foramen ovale was, called the fossa ovalis. [7]

The embryonic heart begins beating at around 22 days after conception (5 weeks after the last normal menstrual period, LMP). It starts to beat at a rate near to the mother's which is about 75–80 beats per minute (bpm). The embryonic heart rate then accelerates and reaches a peak rate of 165–185 bpm early in the early 7th week (early 9th week after the LMP). [36] [37] After 9 weeks (start of the fetal stage) it starts to decelerate, slowing to around 145 (±25) bpm at birth. There is no difference in female and male heart rates before birth. [38]

Blood flow

The heart functions as a pump in the circulatory system to provide a continuous flow of blood throughout the body. This circulation consists of the systemic circulation to and from the body and the pulmonary circulation to and from the lungs. Blood in the pulmonary circulation exchanges carbon dioxide for oxygen in the lungs through the process of respiration. The systemic circulation then transports oxygen to the body and returns carbon dioxide and relatively deoxygenated blood to the heart for transfer to the lungs. [7]

The right heart collects deoxygenated blood from two large veins, the superior and inferior venae cavae. Blood collects in the right and left atrium continuously. [7] The superior vena cava drains blood from above the diaphragm and empties into the upper back part of the right atrium. The inferior vena cava drains the blood from below the diaphragm and empties into the back part of the atrium below the opening for the superior vena cava. Immediately above and to the middle of the opening of the inferior vena cava is the opening of the thin-walled coronary sinus. [7] Additionally, the coronary sinus returns deoxygenated blood from the myocardium to the right atrium. The blood collects in the right atrium. When the right atrium contracts, the blood is pumped through the tricuspid valve into the right ventricle. As the right ventricle contracts, the tricuspid valve closes and the blood is pumped into the pulmonary trunk through the pulmonary valve. The pulmonary trunk divides into pulmonary arteries and progressively smaller arteries throughout the lungs, until it reaches capillaries. As these pass by alveoli carbon dioxide is exchanged for oxygen. This happens through the passive process of diffusion.

In the left heart, oxygenated blood is returned to the left atrium via the pulmonary veins. It is then pumped into the left ventricle through the mitral valve and into the aorta through the aortic valve for systemic circulation. The aorta is a large artery that branches into many smaller arteries, arterioles, and ultimately capillaries. In the capillaries, oxygen and nutrients from blood are supplied to body cells for metabolism, and exchanged for carbon dioxide and waste products. [7] Capillary blood, now deoxygenated, travels into venules and veins that ultimately collect in the superior and inferior vena cavae, and into the right heart.

Cardiac cycle

The cardiac cycle refers to the sequence of events in which the heart contracts and relaxes with every heartbeat. [9] The period of time during which the ventricles contract, forcing blood out into the aorta and main pulmonary artery, is known as systole, while the period during which the ventricles relax and refill with blood is known as diastole. The atria and ventricles work in concert, so in systole when the ventricles are contracting, the atria are relaxed and collecting blood. When the ventricles are relaxed in diastole, the atria contract to pump blood to the ventricles. This coordination ensures blood is pumped efficiently to the body. [7]

At the beginning of the cardiac cycle, the ventricles are relaxing. As they do so, they are filled by blood passing through the open mitral and tricuspid valves. After the ventricles have completed most of their filling, the atria contract, forcing further blood into the ventricles and priming the pump. Next, the ventricles start to contract. As the pressure rises within the cavities of the ventricles, the mitral and tricuspid valves are forced shut. As the pressure within the ventricles rises further, exceeding the pressure with the aorta and pulmonary arteries, the aortic and pulmonary valves open. Blood is ejected from the heart, causing the pressure within the ventricles to fall. Simultaneously, the atria refill as blood flows into the right atrium through the superior and inferior vena cavae, and into the left atrium through the pulmonary veins. Finally, when the pressure within the ventricles falls below the pressure within the aorta and pulmonary arteries, the aortic and pulmonary valves close. The ventricles start to relax, the mitral and tricuspid valves open, and the cycle begins again. [9]

Cardiac output

Cardiac output (CO) is a measurement of the amount of blood pumped by each ventricle (stroke volume) in one minute. This is calculated by multiplying the stroke volume (SV) by the beats per minute of the heart rate (HR). So that: CO = SV x HR. [7] The cardiac output is normalized to body size through body surface area and is called the cardiac index.

The average cardiac output, using an average stroke volume of about 70mL, is 5.25 L/min, with a normal range of 4.0–8.0 L/min. [7] The stroke volume is normally measured using an echocardiogram and can be influenced by the size of the heart, physical and mental condition of the individual, sex, contractility, duration of contraction, preload and afterload. [7]

Preload refers to the filling pressure of the atria at the end of diastole, when the ventricles are at their fullest. A main factor is how long it takes the ventricles to fill: if the ventricles contract more frequently, then there is less time to fill and the preload will be less. [7] Preload can also be affected by a person's blood volume. The force of each contraction of the heart muscle is proportional to the preload, described as the Frank-Starling mechanism. This states that the force of contraction is directly proportional to the initial length of muscle fiber, meaning a ventricle will contract more forcefully, the more it is stretched. [7] [39]

Afterload, or how much pressure the heart must generate to eject blood at systole, is influenced by vascular resistance. It can be influenced by narrowing of the heart valves (stenosis) or contraction or relaxation of the peripheral blood vessels. [7]

The strength of heart muscle contractions controls the stroke volume. This can be influenced positively or negatively by agents termed inotropes. [40] These agents can be a result of changes within the body, or be given as drugs as part of treatment for a medical disorder, or as a form of life support, particularly in intensive care units. Inotropes that increase the force of contraction are "positive" inotropes, and include sympathetic agents such as adrenaline, noradrenaline and dopamine. [41] "Negative" inotropes decrease the force of contraction and include calcium channel blockers. [40]

Electrical conduction

The normal rhythmical heart beat, called sinus rhythm, is established by the heart's own pacemaker, the sinoatrial node (also known as the sinus node or the SA node). Here an electrical signal is created that travels through the heart, causing the heart muscle to contract. The sinoatrial node is found in the upper part of the right atrium near to the junction with the superior vena cava. [42] The electrical signal generated by the sinoatrial node travels through the right atrium in a radial way that is not completely understood. It travels to the left atrium via Bachmann's bundle, such that the muscles of the left and right atria contract together. [43] [44] [45] The signal then travels to the atrioventricular node. This is found at the bottom of the right atrium in the atrioventricular septum—the boundary between the right atrium and the left ventricle. The septum is part of the cardiac skeleton, tissue within the heart that the electrical signal cannot pass through, which forces the signal to pass through the atrioventricular node only. [7] The signal then travels along the bundle of His to left and right bundle branches through to the ventricles of the heart. In the ventricles the signal is carried by specialized tissue called the Purkinje fibers which then transmit the electric charge to the heart muscle. [46]

Heart rate

The normal resting heart rate is called the sinus rhythm, created and sustained by the sinoatrial node, a group of pacemaking cells found in the wall of the right atrium. Cells in the sinoatrial node do this by creating an action potential. The cardiac action potential is created by the movement of specific electrolytes into and out of the pacemaker cells. The action potential then spreads to nearby cells. [47]

When the sinoatrial cells are resting, they have a negative charge on their membranes. However a rapid influx of sodium ions causes the membrane's charge to become positive. This is called depolarisation and occurs spontaneously. [7] Once the cell has a sufficiently high charge, the sodium channels close and calcium ions then begin to enter the cell, shortly after which potassium begins to leave it. All the ions travel through ion channels in the membrane of the sinoatrial cells. The potassium and calcium start to move out of and into the cell only once it has a sufficiently high charge, and so are called voltage-gated. Shortly after this, the calcium channels close and potassium channels open, allowing potassium to leave the cell. This causes the cell to have a negative resting charge and is called repolarization. When the membrane potential reaches approximately −60 mV, the potassium channels close and the process may begin again. [7]

The ions move from areas where they are concentrated to where they are not. For this reason sodium moves into the cell from outside, and potassium moves from within the cell to outside the cell. Calcium also plays a critical role. Their influx through slow channels means that the sinoatrial cells have a prolonged "plateau" phase when they have a positive charge. A part of this is called the absolute refractory period. Calcium ions also combine with the regulatory protein troponin C in the troponin complex to enable contraction of the cardiac muscle, and separate from the protein to allow relaxation. [48]

The adult resting heart rate ranges from 60 to 100 bpm. The resting heart rate of a newborn can be 129 beats per minute (bpm) and this gradually decreases until maturity. [49] An athlete's heart rate can be lower than 60 bpm. During exercise the rate can be 150 bpm with maximum rates reaching from 200 to 220 bpm. [7]

Influences

The normal sinus rhythm of the heart, giving the resting heart rate, is influenced by a number of factors. The cardiovascular centres in the brainstem that control the sympathetic and parasympathetic influences to the heart through the vagus nerve and sympathetic trunk. [50] These cardiovascular centres receive input from a series of receptors including baroreceptors, sensing stretch the stretching of blood vessels and chemoreceptors, sensing the amount of oxygen and carbon dioxide in the blood and its pH. Through a series of reflexes these help regulate and sustain blood flow. [7]

Baroreceptors are stretch receptors located in the aortic sinus, carotid bodies, the venae cavae, and other locations, including pulmonary vessels and the right side of the heart itself. Baroreceptors fire at a rate determined by how much they are stretched, [51] which is influenced by blood pressure, level of physical activity, and the relative distribution of blood. With increased pressure and stretch, the rate of baroreceptor firing increases, and the cardiac centers decrease sympathetic stimulation and increase parasympathetic stimulation. As pressure and stretch decrease, the rate of baroreceptor firing decreases, and the cardiac centers increase sympathetic stimulation and decrease parasympathetic stimulation. [7] There is a similar reflex, called the atrial reflex or Bainbridge reflex, associated with varying rates of blood flow to the atria. Increased venous return stretches the walls of the atria where specialized baroreceptors are located. However, as the atrial baroreceptors increase their rate of firing and as they stretch due to the increased blood pressure, the cardiac center responds by increasing sympathetic stimulation and inhibiting parasympathetic stimulation to increase heart rate. The opposite is also true. [7] Chemoreceptors present in the carotid body or adjacent to the aorta in an aortic body respond to the blood's oxygen, carbon dioxide levels. Low oxygen or high carbon dioxide will stimulate firing of the receptors. [52]

Exercise and fitness levels, age, body temperature, basal metabolic rate, and even a person's emotional state can all affect the heart rate. High levels of the hormones epinephrine, norepinephrine, and thyroid hormones can increase the heart rate. The levels of electrolytes including calcium, potassium, and sodium can also influence the speed and regularity of the heart rate low blood oxygen, low blood pressure and dehydration may increase it. [7]

Diseases

Cardiovascular diseases, which include diseases of the heart, are the leading cause of death worldwide. [53] The majority of cardiovascular disease is noncommunicable and related to lifestyle and other factors, becoming more prevalent with ageing. [53] Heart disease is a major cause of death, accounting for an average of 30% of all deaths in 2008, globally. [11] This rate varies from a lower 28% to a high 40% in high-income countries. [12] Doctors that specialise in the heart are called cardiologists. Many other medical professionals are involved in treating diseases of the heart, including doctors such as general practitioners, cardiothoracic surgeons and intensivists, and allied health practitioners including physiotherapists and dieticians. [54]

Ischaemic heart disease

Coronary artery disease, also known as ischaemic heart disease, is caused by atherosclerosis—a build-up of fatty material along the inner walls of the arteries. These fatty deposits known as atherosclerotic plaques narrow the coronary arteries, and if severe may reduce blood flow to the heart. [55] If a narrowing (or stenosis) is relatively minor then the patient may not experience any symptoms. Severe narrowings may cause chest pain (angina) or breathlessness during exercise or even at rest. The thin covering of an atherosclerotic plaque can rupture, exposing the fatty centre to the circulating blood. In this case a clot or thrombus can form, blocking the artery, and restricting blood flow to an area of heart muscle causing a myocardial infarction (a heart attack) or unstable angina. [56] In the worst case this may cause cardiac arrest, a sudden and utter loss of output from the heart. [57] Obesity, high blood pressure, uncontrolled diabetes, smoking and high cholesterol can all increase the risk of developing atherosclerosis and coronary artery disease. [53] [55]

Heart failure

Heart failure is defined as a condition in which the heart is unable to pump enough blood to meet the demands of the body. [58] Patients with heart failure may experience breathlessness especially when lying flat, as well as ankle swelling, known as peripheral oedema. Heart failure is the end result of many diseases affecting the heart, but is most commonly associated with ischaemic heart disease, valvular heart disease, or high blood pressure. Less common causes include various cardiomyopathies. Heart failure is frequently associated with weakness of the heart muscle in the ventricles (systolic heart failure), but can also be seen in patients with heart muscle that is strong but stiff (diastolic heart failure). The condition may affect the left ventricle (causing predominantly breathlessness), the right ventricle (causing predominantly swelling of the legs and an elevated jugular venous pressure), or both ventricles. Patients with heart failure are at higher risk of developing dangerous heart rhythm disturbances or arrhythmias. [58]

Cardiomyopathies

Cardiomyopathies are diseases affecting the muscle of the heart. Some cause abnormal thickening of the heart muscle (hypertrophic cardiomyopathy), some cause the heart to abnormally expand and weaken (dilated cardiomyopathy), some cause the heart muscle to become stiff and unable to fully relax between contractions (restrictive cardiomyopathy) and some make the heart prone to abnormal heart rhythms (arrhythmogenic cardiomyopathy). These conditions are often genetic and can be inherited, but some such as dilated cardiomyopathy may be caused by damage from toxins such as alcohol. Some cardiomyopathies such as hypertrophic cardiomopathy are linked to a higher risk of sudden cardiac death, particularly in athletes. [7] Many cardiomyopathies can lead to heart failure in the later stages of the disease. [58]

Valvular heart disease

Healthy heart valves allow blood to flow easily in one direction, but prevent it from flowing in the other direction. Diseased heart valves may have a narrow opening and therefore restrict the flow of blood in the forward direction (referred to as a stenotic valve), or may allow blood to leak in the reverse direction (referred to as valvular regurgitation). Valvular heart disease may cause breathlessness, blackouts, or chest pain, but may be asymptomatic and only detected on a routine examination by hearing abnormal heart sounds or a heart murmur. In the developed world, valvular heart disease is most commonly caused by degeneration secondary to old age, but may also be caused by infection of the heart valves (endocarditis). In some parts of the world rheumatic heart disease is a major cause of valvular heart disease, typically leading to mitral or aortic stenosis and caused by the body's immune system reacting to a streptococcal throat infection. [59] [60]

Cardiac arrhythmias

While in the healthy heart, waves of electrical impulses originate in the sinus node before spreading to the rest of the atria, the atrioventricular node, and finally the ventricles (referred to as a normal sinus rhythm), this normal rhythm can be disrupted. Abnormal heart rhythms or arrhythmias may be asymptomatic or may cause palpitations, blackouts, or breathlessness. Some types of arrhythmia such as atrial fibrillation increase the long term risk of stroke. [61]

Some arrhythmias cause the heart to beat abnormally slowly, referred to as a bradycardia or bradyarrhythmia. This may be caused by an abnormally slow sinus node or damage within the cardiac conduction system (heart block). [62] In other arrhythmias the heart may beat abnormally rapidly, referred to as a tachycardia or tachyarrhythmia. These arrhythmias can take many forms and can originate from different structures within the heart—some arise from the atria (e.g. atrial flutter), some from the atrioventricular node (e.g. AV nodal re-entrant tachycardia) whilst others arise from the ventricles (e.g. ventricular tachycardia). Some tachyarrhythmias are caused by scarring within the heart (e.g. some forms of ventricular tachycardia), others by an irritable focus (e.g. focal atrial tachycardia), while others are caused by additional abnormal conduction tissue that has been present since birth (e.g. Wolff-Parkinson-White syndrome). The most dangerous form of heart racing is ventricular fibrillation, in which the ventricles quiver rather than contract, and which if untreated is rapidly fatal. [63]

Pericardial disease

The sack which surrounds the heart, called the pericardium, can become inflamed in a condition known as pericarditis. This condition typically causes chest pain that may spread to the back, and is often caused by a viral infection (glandular fever, cytomegalovirus, or coxsackievirus). Fluid can build up within the pericardial sack, referred to as a pericardial effusion. Pericardial effusions often occur secondary to pericarditis, kidney failure, or tumours, and frequently do not cause any symptoms. However, large effusions or effusions which accumulate rapidly can compress the heart in a condition known as cardiac tamponade, causing breathlessness and potentially fatal low blood pressure. Fluid can be removed from the pericardial space for diagnosis or to relieve tamponade using a syringe in a procedure called pericardiocentesis. [64]

Congenital heart disease

Some people are born with hearts that are abnormal and these abnormalities are known as congenital heart defects. They may range from the relatively minor (e.g. patent foramen ovale, arguably a variant of normal) to serious life-threatening abnormalities (e.g. hypoplastic left heart syndrome). Common abnormalities include those that affect the heart muscle that separates the two side of the heart (a 'hole in the heart' e.g. ventricular septal defect). Other defects include those affecting the heart valves (e.g. congenital aortic stenosis), or the main blood vessels that lead from the heart (e.g. coarctation of the aorta). More complex syndromes are seen that affect more than one part of the heart (e.g. Tetralogy of Fallot).

Some congenital heart defects allow blood that is low in oxygen that would normally be returned to the lungs to instead be pumped back to the rest of the body. These are known as cyanotic congenital heart defects and are often more serious. Major congenital heart defects are often picked up in childhood, shortly after birth, or even before a child is born (e.g. transposition of the great arteries), causing breathlessness and a lower rate of growth. More minor forms of congenital heart disease may remain undetected for many years and only reveal themselves in adult life (e.g. atrial septal defect). [65] [66]

Diagnosis

Heart disease is diagnosed by the taking of a medical history, a cardiac examination, and further investigations, including blood tests, echocardiograms, ECGs and imaging. Other invasive procedures such as cardiac catheterisation can also play a role. [67]

Examination

The cardiac examination includes inspection, feeling the chest with the hands (palpation) and listening with a stethoscope (auscultation). [68] [69] It involves assessment of signs that may be visible on a person's hands (such as splinter haemorrhages), joints and other areas. A person's pulse is taken, usually at the radial artery near the wrist, in order to assess for the rhythm and strength of the pulse. The blood pressure is taken, using either a manual or automatic sphygmomanometer or using a more invasive measurement from within the artery. Any elevation of the jugular venous pulse is noted. A person's chest is felt for any transmitted vibrations from the heart, and then listened to with a stethoscope.

Heart sounds

Typically, healthy hearts have only two audible heart sounds, called S1 and S2. The first heart sound S1, is the sound created by the closing of the atrioventricular valves during ventricular contraction and is normally described as "lub". The second heart sound, S2, is the sound of the semilunar valves closing during ventricular diastole and is described as "dub". [7] Each sound consists of two components, reflecting the slight difference in time as the two valves close. [70] S2 may split into two distinct sounds, either as a result of inspiration or different valvular or cardiac problems. [70] Additional heart sounds may also be present and these give rise to gallop rhythms. A third heart sound, S3 usually indicates an increase in ventricular blood volume. A fourth heart sound S4 is referred to as an atrial gallop and is produced by the sound of blood being forced into a stiff ventricle. The combined presence of S3 and S4 give a quadruple gallop. [7]

Heart murmurs are abnormal heart sounds which can be either related to disease or benign, and there are several kinds. [71] There are normally two heart sounds, and abnormal heart sounds can either be extra sounds, or "murmurs" related to the flow of blood between the sounds. Murmurs are graded by volume, from 1 (the quietest), to 6 (the loudest), and evaluated by their relationship to the heart sounds, position in the cardiac cycle, and additional features such as their radiation to other sites, changes with a person's position, the frequency of the sound as determined by the side of the stethoscope by which they are heard, and site at which they are heard loudest. [71] Murmurs may be caused by damaged heart valves, congenital heart disease such as ventricular septal defects, or may be heard in normal hearts. A different type of sound, a pericardial friction rub can be heard in cases of pericarditis where the inflamed membranes can rub together.

Blood tests

Blood tests play an important role in the diagnosis and treatment of many cardiovascular conditions.

Troponin is a sensitive biomarker for a heart with insufficient blood supply. It is released 4–6 hours after injury, and usually peaks at about 12–24 hours. [41] Two tests of troponin are often taken—one at the time of initial presentation, and another within 3–6 hours, [72] with either a high level or a significant rise being diagnostic. A test for brain natriuretic peptide (BNP) can be used to evaluate for the presence of heart failure, and rises when there is increased demand on the left ventricle. These tests are considered biomarkers because they are highly specific for cardiac disease. [73] Testing for the MB form of creatine kinase provides information about the heart's blood supply, but is used less frequently because it is less specific and sensitive. [74]

Other blood tests are often taken to help understand a person's general health and risk factors that may contribute to heart disease. These often include a full blood count investigating for anaemia, and basic metabolic panel that may reveal any disturbances in electrolytes. A coagulation screen is often required to ensure that the right level of anticoagulation is given. Fasting lipids and fasting blood glucose (or an HbA1c level) are often ordered to evaluate a person's cholesterol and diabetes status, respectively. [75]

Electrocardiogram

Using surface electrodes on the body, it is possible to record the electrical activity of the heart. This tracing of the electrical signal is the electrocardiogram (ECG) or (EKG). An ECG is a bedside test and involves the placement of ten leads on the body. This produces a "12 lead" ECG (three extra leads are calculated mathematically, and one lead is a ground). [76]

There are five prominent features on the ECG: the P wave (atrial depolarisation), the QRS complex (ventricular depolarisation [h] ) and the T wave (ventricular repolarisation). [7] As the heart cells contract, they create a current that travels through the heart. A downward deflection on the ECG implies cells are becoming more positive in charge ("depolarising") in the direction of that lead, whereas an upward inflection implies cells are becoming more negative ("repolarising") in the direction of the lead. This depends on the position of the lead, so if a wave of depolarising moved from left to right, a lead on the left would show a negative deflection, and a lead on the right would show a positive deflection. The ECG is a useful tool in detecting rhythm disturbances and in detecting insufficient blood supply to the heart. [76] Sometimes abnormalities are suspected, but not immediately visible on the ECG. Testing when exercising can be used to provoke an abnormality, or an ECG can be worn for a longer period such as a 24-hour Holter monitor if a suspected rhythm abnormality is not present at the time of assessment. [76]

Imaging

Several imaging methods can be used to assess the anatomy and function of the heart, including ultrasound (echocardiography), angiography, CT scans, MRI and PET. An echocardiogram is an ultrasound of the heart used to measure the heart's function, assess for valve disease, and look for any abnormalities. Echocardiography can be conducted by a probe on the chest ("transthoracic") or by a probe in the esophagus ("transoesophageal"). A typical echocardiography report will include information about the width of the valves noting any stenosis, whether there is any backflow of blood (regurgitation) and information about the blood volumes at the end of systole and diastole, including an ejection fraction, which describes how much blood is ejected from the left and right ventricles after systole. Ejection fraction can then be obtained by dividing the volume ejected by the heart (stroke volume) by the volume of the filled heart (end-diastolic volume). [77] Echocardiograms can also be conducted under circumstances when the body is more stressed, in order to examine for signs of lack of blood supply. This cardiac stress test involves either direct exercise, or where this is not possible, injection of a drug such as dobutamine. [69]

CT scans, chest X-rays and other forms of imaging can help evaluate the heart's size, evaluate for signs of pulmonary oedema, and indicate whether there is fluid around the heart. They are also useful for evaluating the aorta, the major blood vessel which leaves the heart. [69]

Treatment

Diseases affecting the heart can be treated by a variety of methods including lifestyle modification, drug treatment, and surgery.

Ischaemic heart disease

Narrowings of the coronary arteries (ischaemic heart disease) are treated to relieve symptoms of chest pain caused by a partially narrowed artery (angina pectoris), to minimise heart muscle damage when an artery is completely occluded (myocardial infarction), or to prevent a myocardial infarction from occurring. Medications to improve angina symptoms include nitroglycerin, beta blockers, and calcium channel blockers, while preventative treatments include antiplatelets such as aspirin and statins, lifestyle measures such as stopping smoking and weight loss, and treatment of risk factors such as high blood pressure and diabetes. [78]

In addition to using medications, narrowed heart arteries can be treated by expanding the narrowings or redirecting the flow of blood to bypass an obstruction. This may be performed using a percutaneous coronary intervention, during which narrowings can be expanded by passing small balloon-tipped wires into the coronary arteries, inflating the balloon to expand the narrowing, and sometimes leaving behind a metal scaffold known as a stent to keep the artery open. [79]

If the narrowings in coronary arteries are unsuitable for treatment with a percutaneous coronary intervention, open surgery may be required. A coronary artery bypass graft can be performed, whereby a blood vessel from another part of the body (the saphenous vein, radial artery, or internal mammary artery) is used to redirect blood from a point before the narrowing (typically the aorta) to a point beyond the obstruction. [79] [80]

Valvular heart disease

Diseased heart valves that have become abnormally narrow or abnormally leaky may require surgery. This is traditionally performed as an open surgical procedure to replace the damaged heart valve with a tissue or metallic prosthetic valve. In some circumstances, the tricuspid or mitral valves can be repaired surgically, avoiding the need for a valve replacement. Heart valves can also be treated percutaneously, using techniques that share many similarities with percutaneous coronary intervention. Transcatheter aortic valve replacement is increasingly used for patients consider very high risk for open valve replacement. [59]

Cardiac arrhythmias

Abnormal heart rhythms (arrhythmias) can be treated using antiarrhythmic drugs. These may work by manipulating the flow of electrolytes across the cell membrane (such as calcium channel blockers, sodium channel blockers, amiodarone, or digoxin), or modify the autonomic nervous system's effect on the heart (beta blockers and atropine). In some arrhythmias such as atrial fibrillation which increase the risk of stroke, this risk can be reduced using anticoagulants such as warfarin or novel oral anticoagulants. [61]

If medications fail to control an arrhythmia, another treatment option may be catheter ablation. In these procedures, wires are passed from a vein or artery in the leg to the heart to find the abnormal area of tissue that is causing the arrhythmia. The abnormal tissue can be intentionally damaged, or ablated, by heating or freezing to prevent further heart rhythm disturbances. Whilst the majority of arrhythmias can be treated using minimally invasive catheter techniques, some arrhythmias (particularly atrial fibrillation) can also be treated using open or thoracoscopic surgery, either at the time of other cardiac surgery or as a standalone procedure. A cardioversion, whereby an electric shock is used to stun the heart out of an abnormal rhythm, may also be used.

Cardiac devices in the form of pacemakers or implantable defibrillators may also be required to treat arrhythmias. Pacemakers, comprising a small battery powered generator implanted under the skin and one or more leads that extend to the heart, are most commonly used to treat abnormally slow heart rhythms. [62] Implantable defibrillators are used to treat serious life-threatening rapid heart rhythms. These devices monitor the heart, and if dangerous heart racing is detected can automatically deliver a shock to restore the heart to a normal rhythm. Implantable defibrillators are most commonly used in patients with heart failure, cardiomyopathies, or inherited arrhythmia syndromes.

Heart failure

As well as addressing the underlying cause for a patient's heart failure (most commonly ischaemic heart disease or hypertension), the mainstay of heart failure treatment is with medication. These include drugs to prevent fluid from accumulating in the lungs by increasing the amount of urine a patient produces (diuretics), and drugs that attempt to preserve the pumping function of the heart (beta blockers, ACE inhibitors and mineralocorticoid receptor antagonists). [58]

In some patients with heart failure, a specialised pacemaker known as cardiac resynchronisation therapy can be used to improve the heart's pumping efficiency. [62] These devices are frequently combined with a defibrillator. In very severe cases of heart failure, a small pump called a ventricular assist device may be implanted which supplements the heart's own pumping ability. In the most severe cases, a cardiac transplant may be considered. [58]

Ancient

Humans have known about the heart since ancient times, although its precise function and anatomy were not clearly understood. [81] From the primarily religious views of earlier societies towards the heart, ancient Greeks are considered to have been the primary seat of scientific understanding of the heart in the ancient world. [82] [83] [84] Aristotle considered the heart to be the organ responsible for creating blood Plato considered the heart as the source of circulating blood and Hippocrates noted blood circulating cyclically from the body through the heart to the lungs. [82] [84] Erasistratos (304–250 BCE) noted the heart as a pump, causing dilation of blood vessels, and noted that arteries and veins both radiate from the heart, becoming progressively smaller with distance, although he believed they were filled with air and not blood. He also discovered the heart valves. [82]

The Greek physician Galen (2nd century CE) knew blood vessels carried blood and identified venous (dark red) and arterial (brighter and thinner) blood, each with distinct and separate functions. [82] Galen, noting the heart as the hottest organ in the body, concluded that it provided heat to the body. [84] The heart did not pump blood around, the heart's motion sucked blood in during diastole and the blood moved by the pulsation of the arteries themselves. [84] Galen believed the arterial blood was created by venous blood passing from the left ventricle to the right through 'pores' between the ventricles. [81] Air from the lungs passed from the lungs via the pulmonary artery to the left side of the heart and created arterial blood. [84]

These ideas went unchallenged for almost a thousand years. [81] [84]

Pre-modern

The earliest descriptions of the coronary and pulmonary circulation systems can be found in the Commentary on Anatomy in Avicenna's Canon, published in 1242 by Ibn al-Nafis. [85] In his manuscript, al-Nafis wrote that blood passes through the pulmonary circulation instead of moving from the right to the left ventricle as previously believed by Galen. [86] His work was later translated into Latin by Andrea Alpago. [87]

In Europe, the teachings of Galen continued to dominate the academic community and his doctrines were adopted as the official canon of the Church. Andreas Vesalius questioned some of Galen's beliefs of the heart in De humani corporis fabrica (1543), but his magnum opus was interpreted as a challenge to the authorities and he was subjected to a number of attacks. [88] Michael Servetus wrote in Christianismi Restitutio (1553) that blood flows from one side of the heart to the other via the lungs. [88]

Modern

A breakthrough in understanding the flow of blood through the heart and body came with the publication of De Motu Cordis (1628) by the English physician William Harvey. Harvey's book completely describes the systemic circulation and the mechanical force of the heart, leading to an overhaul of the Galenic doctrines. [84] Otto Frank (1865–1944) was a German physiologist among his many published works are detailed studies of this important heart relationship. Ernest Starling (1866–1927) was an important English physiologist who also studied the heart. Although they worked largely independently, their combined efforts and similar conclusions have been recognized in the name "Frank–Starling mechanism". [7]

Although Purkinje fibers and the bundle of His were discovered as early as the 19th century, their specific role in the electrical conduction system of the heart remained unknown until Sunao Tawara published his monograph, titled Das Reizleitungssystem des Säugetierherzens, in 1906. Tawara's discovery of the atrioventricular node prompted Arthur Keith and Martin Flack to look for similar structures in the heart, leading to their discovery of the sinoatrial node several months later. These structures form the anatomical basis of the electrocardiogram, whose inventor, Willem Einthoven, was awarded the Nobel Prize in Medicine or Physiology in 1924. [89]

The first successful heart transplantation was performed in 1967 by the South African surgeon Christiaan Barnard at Groote Schuur Hospital in Cape Town. This marked an important milestone in cardiac surgery, capturing the attention of both the medical profession and the world at large. However, long-term survival rates of patients were initially very low. Louis Washkansky, the first recipient of a donated heart, died 18 days after the operation while other patients did not survive for more than a few weeks. [90] The American surgeon Norman Shumway has been credited for his efforts to improve transplantation techniques, along with pioneers Richard Lower, Vladimir Demikhov and Adrian Kantrowitz. As of March 2000, more than 55,000 heart transplantations have been performed worldwide. [91]

By the middle of the 20th century, heart disease had surpassed infectious disease as the leading cause of death in the United States, and it is currently the leading cause of deaths worldwide. Since 1948, the ongoing Framingham Heart Study has shed light on the effects of various influences on the heart, including diet, exercise, and common medications such as aspirin. Although the introduction of ACE inhibitors and beta blockers has improved the management of chronic heart failure, the disease continues to be an enormous medical and societal burden, with 30 to 40% of patients dying within a year of receiving the diagnosis. [92]

Symbolism

As one of the vital organs, the heart was long identified as the center of the entire body, the seat of life, or emotion, or reason, will, intellect, purpose or the mind. [93] The heart is an emblematic symbol in many religions, signifying "truth, conscience or moral courage in many religions—the temple or throne of God in Islamic and Judeo-Christian thought the divine centre, or atman, and the third eye of transcendent wisdom in Hinduism the diamond of purity and essence of the Buddha the Taoist centre of understanding." [93]

In the Hebrew Bible, the word for heart, lev, is used in these meanings, as the seat of emotion, the mind, and referring to the anatomical organ. It is also connected in function and symbolism to the stomach. [94]

An important part of the concept of the soul in Ancient Egyptian religion was thought to be the heart, or ib. The ib or metaphysical heart was believed to be formed from one drop of blood from the child's mother's heart, taken at conception. [95] To ancient Egyptians, the heart was the seat of emotion, thought, will, and intention. This is evidenced by Egyptian expressions which incorporate the word ib, such as Awi-ib for "happy" (literally, "long of heart"), Xak-ib for "estranged" (literally, "truncated of heart"). [96] In Egyptian religion, the heart was the key to the afterlife. It was conceived as surviving death in the nether world, where it gave evidence for, or against, its possessor. It was thought that the heart was examined by Anubis and a variety of deities during the Weighing of the Heart ceremony. If the heart weighed more than the feather of Maat, which symbolized the ideal standard of behavior. If the scales balanced, it meant the heart's possessor had lived a just life and could enter the afterlife if the heart was heavier, it would be devoured by the monster Ammit. [97]

The Chinese character for "heart", 心, derives from a comparatively realistic depiction of a heart (indicating the heart chambers) in seal script. [98] The Chinese word xīn also takes the metaphorical meanings of "mind", "intention", or "core". [99] In Chinese medicine, the heart is seen as the center of 神 shén "spirit, consciousness". [100] The heart is associated with the small intestine, tongue, governs the six organs and five viscera, and belongs to fire in the five elements. [101]

The Sanskrit word for heart is hṛd or hṛdaya, found in the oldest surviving Sanskrit text, the Rigveda. In Sanskrit, it may mean both the anatomical object and "mind" or "soul", representing the seat of emotion. Hrd may be a cognate of the word for heart in Greek, Latin, and English. [102] [103]

Many classical philosophers and scientists, including Aristotle, considered the heart the seat of thought, reason, or emotion, often disregarding the brain as contributing to those functions. [104] The identification of the heart as the seat of emotions in particular is due to the Roman physician Galen, who also located the seat of the passions in the liver, and the seat of reason in the brain. [105]

The heart also played a role in the Aztec system of belief. The most common form of human sacrifice practiced by the Aztecs was heart-extraction. The Aztec believed that the heart (tona) was both the seat of the individual and a fragment of the Sun's heat (istli). To this day, the Nahua consider the Sun to be a heart-soul (tona-tiuh): "round, hot, pulsating". [106]

In Catholicism, there has been a long tradition of veneration of the heart, stemming from worship of the wounds of Jesus Christ which gained prominence from the mid sixteenth century. [107] This tradition influenced the development of the medieval Christian devotion to the Sacred Heart of Jesus and the parallel veneration of the Immaculate Heart of Mary, made popular by John Eudes. [108]

The expression of a broken heart is a cross-cultural reference to grief for a lost one or to unfulfilled romantic love.

The notion of "Cupid's arrows" is ancient, due to Ovid, but while Ovid describes Cupid as wounding his victims with his arrows, it is not made explicit that it is the heart that is wounded. The familiar iconography of Cupid shooting little heart symbols is a Renaissance theme that became tied to Valentine's day. [93]

Animal hearts are widely consumed as food. As they are almost entirely muscle, they are high in protein. They are often included in dishes with other offal, for example in the pan-Ottoman kokoretsi.

Chicken hearts are considered to be giblets, and are often grilled on skewers: Japanese hāto yakitori, Brazilian churrasco de coração, Indonesian chicken heart satay. [109] They can also be pan-fried, as in Jerusalem mixed grill. In Egyptian cuisine, they can be used, finely chopped, as part of stuffing for chicken. [110] Many recipes combined them with other giblets, such as the Mexican pollo en menudencias [111] and the Russian ragu iz kurinyikh potrokhov. [112]

The hearts of beef, pork, and mutton can generally be interchanged in recipes. As heart is a hard-working muscle, it makes for "firm and rather dry" meat, [113] so is generally slow-cooked. Another way of dealing with toughness is to julienne the meat, as in Chinese stir-fried heart. [114]

Beef heart may be grilled or braised. [115] In the Peruvian anticuchos de corazón, barbecued beef hearts are grilled after being tenderized through long marination in a spice and vinegar mixture. An Australian recipe for "mock goose" is actually braised stuffed beef heart. [116]

Pig heart is stewed, poached, braised, [117] or made into sausage. The Balinese oret is a sort of blood sausage made with pig heart and blood. A French recipe for cœur de porc à l'orange is made of braised heart with an orange sauce.

Other vertebrates

The size of the heart varies among the different animal groups, with hearts in vertebrates ranging from those of the smallest mice (12 mg) to the blue whale (600 kg). [118] In vertebrates, the heart lies in the middle of the ventral part of the body, surrounded by a pericardium. [119] which in some fish may be connected to the peritoneum. [120]

The SA node is found in all amniotes but not in more primitive vertebrates. In these animals, the muscles of the heart are relatively continuous, and the sinus venosus coordinates the beat, which passes in a wave through the remaining chambers. Indeed, since the sinus venosus is incorporated into the right atrium in amniotes, it is likely homologous with the SA node. In teleosts, with their vestigial sinus venosus, the main centre of coordination is, instead, in the atrium. The rate of heartbeat varies enormously between different species, ranging from around 20 beats per minute in codfish to around 600 in hummingbirds [121] and up to 1200 bpm in the ruby-throated hummingbird. [122]

Double circulatory systems

  1. Pulmonary vein
  2. Left atrium
  3. Right atrium
  4. Ventricle
  5. Conus arteriosus
  6. Sinus venosus

Adult amphibians and most reptiles have a double circulatory system, meaning a circulatory system divided into arterial and venous parts. However, the heart itself is not completely separated into two sides. Instead, it is separated into three chambers—two atria and one ventricle. Blood returning from both the systemic circulation and the lungs is returned, and blood is pumped simultaneously into the systemic circulation and the lungs. The double system allows blood to circulate to and from the lungs which deliver oxygenated blood directly to the heart. [123]

In reptiles, the heart is usually situated around the middle of the thorax, and in snakes, usually between the junction of the upper first and second third. There is a heart with three chambers: two atria and one ventricle. The form and function of these hearts are different than mammalian hearts due to the fact that snakes have an elongated body, and thus are affected by different environmental factors. In particular, the snake's heart relative to the position in their body has been influenced greatly by gravity. Therefore, snakes that are larger in size tend to have a higher blood pressure due to gravitational change. This results in the heart being located in different regions of the body that is relative to the snake's body length. [124] The ventricle is incompletely separated into two-halves by a wall (septum), with a considerable gap near the pulmonary artery and aortic openings. In most reptilian species, there appears to be little, if any, mixing between the bloodstreams, so the aorta receives, essentially, only oxygenated blood. [121] [123] The exception to this rule is crocodiles, which have a four-chambered heart. [125]

In the heart of lungfish, the septum extends part-way into the ventricle. This allows for some degree of separation between the de-oxygenated bloodstream destined for the lungs and the oxygenated stream that is delivered to the rest of the body. The absence of such a division in living amphibian species may be partly due to the amount of respiration that occurs through the skin thus, the blood returned to the heart through the venae cavae is already partially oxygenated. As a result, there may be less need for a finer division between the two bloodstreams than in lungfish or other tetrapods. Nonetheless, in at least some species of amphibian, the spongy nature of the ventricle does seem to maintain more of a separation between the bloodstreams. Also, the original valves of the conus arteriosus have been replaced by a spiral valve that divides it into two parallel parts, thereby helping to keep the two bloodstreams separate. [121]

The fully divided heart

Archosaurs (crocodilians and birds) and mammals show complete separation of the heart into two pumps for a total of four heart chambers it is thought that the four-chambered heart of archosaurs evolved independently from that of mammals. In crocodilians, there is a small opening, the foramen of Panizza, at the base of the arterial trunks and there is some degree of mixing between the blood in each side of the heart, during a dive underwater [126] [127] thus, only in birds and mammals are the two streams of blood—those to the pulmonary and systemic circulations—permanently kept entirely separate by a physical barrier. [121]

Fish have what is often described as a two-chambered heart, [128] consisting of one atrium to receive blood and one ventricle to pump it. [129] However, the fish heart has entry and exit compartments that may be called chambers, so it is also sometimes described as three-chambered [129] or four-chambered, [130] depending on what is counted as a chamber. The atrium and ventricle are sometimes considered "true chambers", while the others are considered "accessory chambers". [131]

Primitive fish have a four-chambered heart, but the chambers are arranged sequentially so that this primitive heart is quite unlike the four-chambered hearts of mammals and birds. The first chamber is the sinus venosus, which collects deoxygenated blood from the body through the hepatic and cardinal veins. From here, blood flows into the atrium and then to the powerful muscular ventricle where the main pumping action will take place. The fourth and final chamber is the conus arteriosus, which contains several valves and sends blood to the ventral aorta. The ventral aorta delivers blood to the gills where it is oxygenated and flows, through the dorsal aorta, into the rest of the body. (In tetrapods, the ventral aorta has divided in two one half forms the ascending aorta, while the other forms the pulmonary artery). [121]

In the adult fish, the four chambers are not arranged in a straight row but instead form an S-shape, with the latter two chambers lying above the former two. This relatively simple pattern is found in cartilaginous fish and in the ray-finned fish. In teleosts, the conus arteriosus is very small and can more accurately be described as part of the aorta rather than of the heart proper. The conus arteriosus is not present in any amniotes, presumably having been absorbed into the ventricles over the course of evolution. Similarly, while the sinus venosus is present as a vestigial structure in some reptiles and birds, it is otherwise absorbed into the right atrium and is no longer distinguishable. [121]

Invertebrates

Arthropods and most mollusks have an open circulatory system. In this system, deoxygenated blood collects around the heart in cavities (sinuses). This blood slowly permeates the heart through many small one-way channels. The heart then pumps the blood into the hemocoel, a cavity between the organs. The heart in arthropods is typically a muscular tube that runs the length of the body, under the back and from the base of the head. Instead of blood the circulatory fluid is haemolymph which carries the most commonly used respiratory pigment, copper-based haemocyanin as the oxygen transporter. Haemoglobin is only used by a few arthropods. [132]

In some other invertebrates such as earthworms, the circulatory system is not used to transport oxygen and so is much reduced, having no veins or arteries and consisting of two connected tubes. Oxygen travels by diffusion and there are five small muscular vessels that connect these vessels that contract at the front of the animals that can be thought of as "hearts". [132]

Squids and other cephalopods have two "gill hearts" also known as branchial hearts, and one "systemic heart". The branchial hearts have two atria and one ventricle each, and pump to the gills, whereas the systemic heart pumps to the body. [133] [134]