on 19-Mar-2020 (Thu)

It is composed of four muscular chambers: the main pumping chambers, the left and right ventricles, and the left and right atria, which act like “priming pumps” responsible for the final 20–30% of ventricular filling

The heart lies free in the pericardial sac, attached to mediastinal structures only at the great vessels. During embryologic development, the heart invaginates into the pericardial sac like a fist pushing into a partially inflated balloon

Under normal conditions, approximately 40–50 mL of clear fluid, which probably is an ultrafiltrate of plasma, fills the space between the layers of the pericardial sac.

The left main and right coronary arteries arise from the root of the aorta and provide the principal blood supply to the heart (Figure 10–2).

The large left main coronary artery usually branches into the left anterior descending artery and the circumflex coronary artery.
The left anterior descending coronary artery gives off diagonal and septal branches that supply blood to the anterior wall and septum of the heart, respectively.
The circumflex coronary artery continues around the heart in the left atrioventricular groove and gives off large obtuse marginal arteries that supply blood to the left ventricular free wall.

The right coronary artery travels in the right atrioventricular groove and supplies blood to the right ventricle via acute marginal branches.
The posterior descending artery, which supplies blood to the posterior and inferior walls of the left ventricle, arises from the right coronary artery in 80% of people (right-dominant circulation) and from the circumflex artery in the remainder (left-dominant circulation)

Cells in the sinoatrial (SA) node and the atrioventricular (AV) node have fast pacemaker rates (SA node: 60–100 bpm; AV node: 40–70 bpm), and the His bundle and Purkinje fibers are characterized by rapid rates of conduction

Conduction velocity slows from 1 m/s in atrial tissue to 0.05 m/s in nodal tissue. After the delay in the AV node, the impulse moves rapidly down the His bundle (1 m/s) and Purkinje fibers (4 m/s) to simultaneously depolarize the right and left ventricles

Because normal ventricular depolarization occurs almost simultaneously in the right and left ventricles—usually within 60– 100 ms—the QRS complex is narrow. Although the electrical activity of the small specialized conduction tissues cannot be measured directly from the surface, the interval between the P wave and the start of the QRS complex (PR interval) primarily represents the conduction time of the AV node and His bundle

Myocytes are filled with hundreds of parallel striated bundles termed myofibrils.

Myofibrils are composed of repeating units, termed sarcomeres, that form the major contractile unit of the myocyte (Figure 10–4).

Sarcomeres are complex structures composed of contractile proteins, myosin and actin, which are connected by cross-bridges, and a regulatory protein complex, tropomyosin.

When operating with arrays of different types, the type of the resulting array corresponds to the more general or precise one (a behavior known as upcasting).

Physiology of the Whole Heart

Because the ventricles are the primary physiologic pumps of the heart, analysis has focused on these chambers, particularly the left ventricle. The function of intact ventricles is traditionally studied by evaluating pressure–time and pressure–volume relationships.

At the beginning of the cardiac cycle, the left atrium contracts, forcing additional blood into the left ventricle and giving rise to an a wave on the left atrial pressure tracing. At end diastole, the mitral valve closes, producing the first heart sound (S 1 ), and a brief period of isovolumic contraction follows, during which both the aortic and mitral valves are closed but the left ventricle is actively contracting. When intraventricular pressure rises to the level of aortic pressure, the aortic valve opens and blood flows into the aorta. Beyond this point, the aorta and left ventricle form a contiguous chamber with equal pressures, but left ventricular volume decreases as blood is expelled. Left ventricular contraction stops and ventricular relaxation begins, and end systole is reached when intraventricular pressure falls below aortic pressure. The aortic valve then closes, producing the second heart sound (S 2 )

Throughout systole, blood has slowly accumulated in the left atrium (because the mitral valve is closed), giving rise to the v wave on the left atrial pressure tracing. During the first phase of diastole—isovolumic relaxation—no change in ventricular volume occurs, but continued relaxation of the ventricle leads to an exponential fall in left ventricular pressure. Left ventricular filling begins when left ventricular pressure falls below left atrial pressure and the mitral valve opens. Ventricular relaxation is a relatively long process that begins before the aortic valve closes and extends past the mitral valve opening. The rate and extent of ventricular relaxation depend on multiple factors: heart rate, wall thickness, chamber volume and shape, aortic pressure, sympathetic tone, and presence or absence of myocardial ischemia

Once the mitral valve opens, there is an initial period of rapid filling of the ventricle that contributes 70–80% of blood volume to the ventricle and occurs largely because of the atrioventricular pressure gradient. By mid-diastole, flow into the left ventricle has slowed, and the cardiac cycle begins again with the next atrial contraction. Right ventricular pressure–time analysis is similar but with lower pressures because the impedance to flow in the pulmonary vascular system is much lower than in the systemic circulation

From top downward : pressure (mmHg) in aorta, left ventricle, left atrium, pulmonary artery, right ventricle, right atrium; blood flow (mL/s) in ascending aorta and pulmonary artery; ECG.

Abscissa, time in seconds. (Valvular opening and closing are indicated by AO and AC, respectively, for the aortic valve; MO and MC for the mitral valve; PO and PC for the pulmonary valve; TO and TC for the tricuspid valve.)

Events of the cardiac cycle at a heart rate of 75 bpm.

The phases of the cardiac cycle identified by the numbers at the bottom are as follows:
1, atrial systole;
2, isovolumetric ventricular contraction;
3, ventricular ejection;
4, isovolumetric ventricular relaxation;
5, ventricular filling.

Note that late in systole, aortic pressure actually exceeds left ventricular pressure. However, the momentum of the blood keeps it flowing out of the ventricle for a short period. The pressure relationships in the right ventricle and pulmonary artery are similar.

From top downward : pressure (mmHg) in aorta, left ventricle, left atrium, pulmonary artery, right ventricle, right atrium; blood flow (mL/s) in ascending aorta and pulmonary artery; ECG.

Abscissa, time in seconds. (Valvular opening and closing are indicated by AO and AC, respectively, for the aortic valve; MO and MC for the mitral valve; PO and PC for the pulmonary valve; TO and TC for the tricuspid valve.)

Events of the cardiac cycle at a heart rate of 75 bpm.

The phases of the cardiac cycle identified by the numbers at the bottom are as follows:
1, atrial systole;
2, isovolumetric ventricular contraction;
3, ventricular ejection;
4, isovolumetric ventricular relaxation;
5, ventricular filling.

Note that late in systole, aortic pressure actually exceeds left ventricular pressure. However, the momentum of the blood keeps it flowing out of the ventricle for a short period. The pressure relationships in the right ventricle and pulmonary artery are similar.

During diastole, as ventricular volume increases during both the initial rapid filling period and atrial contraction, ventricular pressure increases (curve da). The shape and position of this curve, the diastolic pressure–volume relationship, depend on relaxation properties of the ventricle, the elastic recoil of the ventricle, and the distensibility of the ventricle. The curve shifts to the left (higher pressure for a given volume) if relaxation of the ventricle is decreased, the ventricle loses elastic recoil, or the ventricle becomes stiffer.

At the beginning of systole, active ventricular contraction begins and volume remains unchanged (isovolumic contraction period) (ab). When left ventricular pressure reaches aortic pressure, the aortic valve opens, and ventricular volume decreases as the ventricle expels its blood (curve bc). At end systole (c), the aortic valve closes and isovolumic relaxation begins (cd). When the mitral valve opens, the ventricle begins filling for the next cardiac cycle, repeating the entire process. The area encompassed by this loop represents the amount of work done by the ventricle during a cardiac cycle.

The position of point c depends on the isovolumic systolic pressure–volume curve. If the ventricle is filled with variable amounts of blood (preloads) and allowed to contract, but the aortic valve is prevented from opening, a relatively linear relationship exists, termed the isovolumic systolic pressure–volume curve (Figure 10–6B). The slope and position of this line describe the inherent contractile state of the ventricle. If contractility is increased by catecholamines or other positive inotropes, the line will shift to the left.

A:Pressure–volume loop for the left ventricle. During diastole, the left ventricle fills and pressure increases along the diastolic pressure–volume curve from d to a.

Line ab represents isometric contraction, and bc the ejection phase of systole.

The aortic valve closes at point c, and pressure drops along cd (isovolumic relaxation), until the mitral valve opens at point d and the cycle repeats.

The distance from b to c represents the stroke volume ejected by that beat.

Point a represents end-diastole, and point c represent end-systole.

B: If the left ventricle is filled by varying amounts (a, a′, a′′) and allowed to undergo isovolumic contraction, a relatively linear relationship, the isovolumic pressure–volume relation, can be defined

The stroke volume depends on three parameters: contractility, afterload, and preload

Changing the contractile state of the heart will change the width of the pressure– volume loop by changing the position of the isovolumic systolic pressure curve. The impedance against which the heart must work (aortic pressure for the left ventricle) is termed afterload; increased afterload will cause a decrease in stroke volume. Preload is the amount of filling of the ventricle at end-diastole. Up to a point, the more a myocyte or ventricular chamber is stretched, the more it will contract (Frank–Starling relationship), so that increased preload will lead to an increase in stroke volume

FIGURE10–7

A:Increasing afterload from b to b′ decreases stroke volume from bc to b′c′.

B: Increasing preload from a to a′ increases stroke volume from bc to b′c′, but at the expense of increased end-diastolic pressure.

C: An increasingly contractile state shifts the isovolumic pressure–volume relationship leftward, increasing stroke volume from bc to b′c′

FIGURE10–7

A:Increasing afterload from b to b′ decreases stroke volume from bc to b′c′.

B: Increasing preload from a to a′ increases stroke volume from bc to b′c′, but at the expense of increased end-diastolic pressure.

C: An increasingly contractile state shifts the isovolumic pressure–volume relationship leftward, increasing stroke volume from bc to b′c′

Briefly, when the myocyte is stimulated, sodium channels on the cell surface membrane (sarcolemma) open, and sodium ions (Na + ) flow down their electrochemical gradient into the cell. This sudden inward surge of ions is responsible for the sharp upstroke of the myocyte action potential (phase 0) (Figure 10–8). A plateau phase follows, during which the cell membrane potential remains relatively unchanged owing to the inward flow of calcium ions (Ca 2+ ) and the outward flow of potassium ions (K + ) through several different specialized potassium channels. Repolarization occurs because of the continued outward flow of K + after the inward flux of Ca 2+ has stopped

Within the cell, the change in membrane potential from the sudden influx of Na + and the subsequent increase in intracellular Ca 2+ causes the sarcoplasmic reticulum to release large numbers of calcium ions via specialized Ca 2+ release channels, although the exact signaling mechanism is unknown. Once in the cytoplasm, however, Ca 2+ released from the sarcoplasmic reticulum binds with the regulatory proteins troponin and tropomyosin. Myosin and actin are then allowed to interact and the cross-bridges between them bend, giving rise to contraction

The process of relaxation is also poorly understood but appears to involve return of Ca 2+ to the sarcoplasmic reticulum via two transmembrane sarcoplasmic reticulum-embedded proteins: Ca 2+ -ATPase and phospholamban. Reuptake of Ca 2+ is an active process that requires adenosine triphosphate (ATP)

FIGURE10–8 Changes in ionic conductances responsible for generating action potentials for ventricular or atrial tissue (right) and a sinus or AV node cell (left).

In nodal cells, rapid Na+ channels are absent, so that the action potential upstroke is much slower.

Diastolic depolarization observed in nodal cells is a result of decreased K+ efflux and slow Na+ and Ca2+ influx. Ca2+ (T): influx via Ca2+ (T) channels; Ca2+ (L): influx via Ca2+ (L) channels.

FIGURE10–9 Initiation of muscle contraction by Ca2+.When Ca2+binds to troponin C, tropomyosin is displaced laterally, exposing the binding site for myosin on actin (dark area). ATP hydrolysis then changes the conformation of the myosin head and fosters its binding to the exposed site. For simplicity, only one of the two heads of the myosin-II molecule is shown.

The action potential of pacemaker cells is different from that described for ventricular and atrial myocytes (see Figure 10–8). Fast sodium channels are absent, so that a rapid phase 0 depolarization is not observed in SA nodal and AV nodal cells. In addition, these cells are characterized by increased automaticity from a relatively rapid spontaneous phase 4 depolarization. A combination of a reduced outward flow of K + and an inward flow of Na + and Ca 2+ via specialized channels appears to be responsible for this dynamic change in membrane potential. Myofibrils are sparse, although present, in the specialized pacemaker cells

Bradycardia

Bradycardia can arise from two basic mechanisms.

First, reduced automaticity of the sinus node can result in slow heart rates or pauses. As shown in Figure 10– 10, if sinus node pacemaker activity ceases, the heart will usually be activated at a slower rate by other cardiac tissues with pacemaker activity. Reduced sinus node automaticity can occur during periods of increased vagal tone (sleep, carotid sinus massage, “common faint”), with increasing age, and secondary to drugs (beta blockers, calcium channel blockers).

Atrioventricular block has been classified as first degree when there is an abnormally long atrioventricular conduction time (PR interval >0.22 s) but activation of the atria and ventricles still demonstrates a 1:1 association.

In second-degree atrioventricular block, some but not all atrial impulses are conducted to the ventricles.

Finally, in third-degree block, there is no association between atrial and ventricular activity

Atrioventricular block can occur with increasing age, with increased vagal input, and as a side effect of certain drugs. Atrioventricular block can sometimes also be observed in congenital disorders, such as muscular dystrophy, tuberous sclerosis, and maternal systemic lupus erythematosus, and in acquired disorders, such as sarcoidosis, gout, Lyme disease, systemic lupus erythematosus, ankylosing spondylitis, and coronary artery disease

Tachycardia

Tachycardias can arise from three basic cellular mechanisms (Figure 10–12).

First, increased automaticity resulting from more rapid phase 4 depolarization can cause rapid heart rate.

Second, if repolarization is delayed (longer plateau period), spontaneous depolarizations (caused by reactivation of sodium or calcium channels) can sometimes occur in phase 3 or phase 4 of the action potential.
These depolarizations are called triggered activity because they depend on the existence of a preceding action potential.
If these depolarizations reach threshold, tachycardia can occur in certain pathologic conditions.

Third, and most commonly, tachycardias can arise from a re-entrant circuit. Any condition that gives rise to parallel but electrically separate regions with different conduction velocities (such as the border zone of a myocardial infarction or an accessory atrioventricular connection) can serve as the substrate for a re-entrant circuit.

The best studied example of re-entrant tachyarrhythmias is Wolff–Parkinson– White syndrome (Figure 10–13).

As mentioned, the AV node normally forms the only electrical connection between the atria and the ventricles. Perhaps because of incomplete formation of the annulus, an accessory atrioventricular connection is found in approximately 1 in 1000 persons.

This accessory pathway is usually composed of normal atrial or ventricular tissue.

Because part of the ventricle is “pre-excited” over the accessory pathway rather than via the AV node, the surface ECG shows a short PR interval and a relatively wide QRS with a slurred upstroke, termed a delta wave.

Because the atria and ventricles are linked by two parallel connections, re-entrant tachycardias are readily initiated. For example, a premature atrial contraction could be blocked in the accessory pathway but still conduct to the ventricles via the AV node. If enough time has elapsed so that the accessory pathway has recovered excitability, the cardiac impulse can travel in retrograde fashion to the atria over the accessory pathway and initiate a re-entrant tachycardia.

FIGURE10–10 Rhythmstripshowingbradycardiaresultingfromsinusnodepause.Atrialactivity (arrows) suddenly ceases, and after approximately 3 s a junctional escape beat is observed (J)

FIGURE10–11 Rhythmstripdemonstratingthird-degree(complete)heartblockwithnoassociation between atrial activity (arrows) and ventricular activity (dots)

FIGURE10–12 Tachyarrhythmias can arise from three different mechanisms.

First,increased automaticity from more rapid phase 4 depolarization can cause arrhythmias.

Second, in certain conditions, spontaneous depolarizations during phase 3 (early after-depolarizations [EAD]) or phase 4 (delayed after- depolarizations [DAD]) can repetitively reach threshold and cause tachycardia.
This appears to be the mechanism of the polymorphic ventricular tachycardia (torsades de pointes) observed in some patients taking procainamide or quinidine and the arrhythmias associated with digoxin toxicity.

Third, the most common mechanism for tachyarrhythmia is re-entry.
In re-entry, two parallel pathways with different conduction properties exist (perhaps at the border zone of a myocardial infarction or a region of myocardial ischemia).
The electrical impulse normally travels down the fast pathway and the slow pathway (shaded region), but at the point where the two pathways converge, the impulse traveling down the slow pathway is blocked since the tissue is refractory from the recent depolarization via the fast pathway (a). However, when a premature beat reaches the circuit, block can occur in the fast pathway, and the impulse will travel down the slow pathway (shaded region) (b). After traveling through the slow pathway, the impulse can then enter the fast pathway in retrograde fashion (which, because of the delay, has recovered excitability) and then re-enter the slow pathway to start a continuous loop of activation, or re-entrant circuit (c)

FIGURE10–13 Re-entrant tachyarrhythmia resulting from Wolff–Parkinson–White syndrome.

A: The first two beats demonstrate sinus rhythm with pre-excitation of the ventricles over an accessory pathway. The large arrows show the delta wave. An atrial premature contraction (APC) blocks in the accessory pathway, which leads to normalization of the QRS, and the atria are activated in retrograde fashion via the accessory pathway (small arrows), and supraventricular tachycardia ensues.

B: The left panel schematically depicts the first two beats of the rhythm strip. The QRS is wide owing to activation of the ventricles over both the AV node and the accessory pathway. The middle panel depicts the atrial premature contraction, which is blocked in the accessory pathway but conducts over the AV node. In the right panel, the atria are activated in retrograde fashion over the accessory pathway, and a re-entrant circuit is initiated.

The best example of tachycardias from triggered activity is long QT syndrome. More than 40 years ago, investigators described several clusters of patients with a congenital syndrome associated with a long QT interval and ventricular arrhythmias. Data have shown that the long QT interval can be a result of several specific ion channel defects. For example, a reduction in potassium channel function leads to a prolonged plateau period (Figure 10–14). The prolonged plateau phase in ventricular tissue leads to a prolonged QT interval. These patients are prone to triggered activity because of the reactivation of sodium and calcium channels (early after depolarizations). Triggered activity in the ventricles can lead to life-threatening ventricular arrhythmias

Regardless of the mechanism, the approach to the immediate clinical management of tachycardias depends on whether the QRS complex is narrow or wide. If the QRS complex is narrow, ventricular depolarization must be occurring normally over the specialized conduction tissues of the heart, and the arrhythmia must be originating at or above the AV node (supraventricular)

A wide QRS complex suggests that ventricular activation is not occurring normally over the specialized conduction tissues of the heart. The tachycardia is arising from ventricular tissue or is a supraventricular tachycardia with aberrant conduction over the His–Purkinje system or an accessory pathway. Criteria have been developed to distinguish between ventricular and supraventricular tachycardia with aberrance

FIGURE10–14 IncertainpatientswithlongQTsyndrome,potassiumchannelfunctionisreduced (diagonal arrows), which leads to prolongation of the action potential of ventricular myocytes and prolongation of the QT interval. In some cases, reactivation of sodium and calcium channels can lead to triggered activity that can initiate life-threatening ventricular arrhythmias.

FIGURE10–15

In supra ventricular tachycardia, the QRS is narrow because the ventricles are depolarized over the normal specialized conduction tissues (light blue region). Five possible arrhythmias are commonly encountered.

First, in atrial fibrillation, multiple microreentrant circuits can lead to chaotic activation of the atrium. Because impulses are reaching the AV node at irregular intervals, ventricular depolarization is irregular.

Second, in atrial flutter, a macroreentrant circuit, traveling up the interatrial septum and down the lateral walls, can activate the atria in a regular fashion at approximately 300 bpm. The AV node can conduct only every other or every third beat, so that the ventricles are depolarized at 150 or 100 bpm.

In AV nodal re-entrant tachycardia, slow and fast pathways exist in the region of the AV node and a microreentrant circuit can be formed.

Fourth, in atrioventricular re-entry, an abnormal connection between the atrium and ventricle exists so that a macroreentrant circuit can be formed with the AV node forming the slow pathway, and the abnormal atrioventricular connection forming the fast pathway.

Finally, in atrial tachycardia, an abnormal focus of atrial activity as a result of either re-entry, triggered activity, or abnormal automaticity can activate the atria in a regular fashion.

FIGURE10–15

In supra ventricular tachycardia, the QRS is narrow because the ventricles are depolarized over the normal specialized conduction tissues (light blue region). Five possible arrhythmias are commonly encountered.

First, in atrial fibrillation, multiple microreentrant circuits can lead to chaotic activation of the atrium. Because impulses are reaching the AV node at irregular intervals, ventricular depolarization is irregular.

Second, in atrial flutter, a macroreentrant circuit, traveling up the interatrial septum and down the lateral walls, can activate the atria in a regular fashion at approximately 300 bpm. The AV node can conduct only every other or every third beat, so that the ventricles are depolarized at 150 or 100 bpm.

In AV nodal re-entrant tachycardia, slow and fast pathways exist in the region of the AV node and a microreentrant circuit can be formed.

Fourth, in atrioventricular re-entry, an abnormal connection between the atrium and ventricle exists so that a macroreentrant circuit can be formed with the AV node forming the slow pathway, and the abnormal atrioventricular connection forming the fast pathway.

Finally, in atrial tachycardia, an abnormal focus of atrial activity as a result of either re-entry, triggered activity, or abnormal automaticity can activate the atria in a regular fashion.