Guyton and Hall Physiology Chapter 9 Cardiac Muscle PDF

CHAPTER 9 UNIT III Cardiac Muscle; The Heart as a Pump and Function of the Heart Valves The heart, shown in Figure 9-1, is...

CHAPTER 9 UNIT III Cardiac Muscle; The Heart as a Pump and Function of the Heart Valves The heart, shown in Figure 9-1, is actually two separate again. Note that cardiac muscle is striated in the same pumps, a right heart that pumps blood through the lungs manner as in skeletal muscle. Furthermore, cardiac mus- and a left heart that pumps blood through the systemic cle has typical myofibrils that contain actin and myosin circulation that provides blood flow to the other organs filaments almost identical to those found in skeletal mus- and tissues of the body. Each of these is a pulsatile, two- cle; these filaments lie side by side and slide during con- chamber pump composed of an atrium and a ventricle. traction in the same manner as occurs in skeletal muscle Each atrium is a weak primer pump for the ventricle, (see Chapter 6). In other ways, however, cardiac muscle is helping to move blood into the ventricle. The ventricles quite different from skeletal muscle, as we shall see. then supply the main pumping force that propels the Left Ventricular Rotation (Twist) Aids Left Ventricular blood either (1) through the pulmonary circulation by the Ejection and Relaxation. The left ventricle is organized right ventricle or (2) through the systemic circulation by into complex muscle fiber layers that run in different di- the left ventricle. The heart is surrounded by a two-layer rections and allow the heart to contract in a twisting mo- sac called the pericardium, which protects the heart and tion during systole. The subepicardial (outer) layer spirals holds it in place. in a leftward direction, and the subendocardial (inner) Special mechanisms in the heart cause a continuing layer spirals in the opposite direction (rightward), causing succession of contractions called cardiac rhythmicity, clockwise rotation of the apex of the heart and counter- transmitting action potentials throughout the cardiac clockwise rotation of the base of the left ventricle (Figure muscle to cause the heart’s rhythmical beat. This rhyth- 9-3). This causes a wringing motion of the left ventricle, mical control system is discussed in Chapter 10. In this pulling the base downward toward the apex during sys- chapter, we explain how the heart operates as a pump, tole (contraction). At the end of systole, the left ventricle beginning with the special features of cardiac muscle is similar to a loaded spring and recoils or untwists during (Video 9-1). diastole (relaxation) to allow blood to enter the pumping chambers rapidly. PHYSIOLOGY OF CARDIAC MUSCLE Cardiac Muscle Is a Syncytium. The dark areas crossing The heart is composed of three major types of cardiac the cardiac muscle fibers in Figure 9-2 are called interca- muscle—atrial muscle, ventricular muscle, and special- lated discs; they are actually cell membranes that separate ized excitatory and conductive muscle fibers. The atrial individual cardiac muscle cells from one another. That is, and ventricular types of muscle contract in much the cardiac muscle fibers are made up of many individual cells same way as skeletal muscle, except that the duration of connected in series and in parallel with one another. contraction is much longer. The specialized excitatory At each intercalated disc, the cell membranes fuse with and conductive fibers of the heart, however, contract fee- one another to form permeable communicating junctions bly because they contain few contractile fibrils; instead, (gap junctions) that allow rapid diffusion of ions. There- they exhibit automatic rhythmical electrical discharge in fore, from a functional point of view, ions move with ease the form of action potentials or conduction of the action in the intracellular fluid along the longitudinal axes of the potentials through the heart, providing an excitatory sys- cardiac muscle fibers so that action potentials travel easily tem that controls the rhythmical beating of the heart. from one cardiac muscle cell to the next, past the interca- lated discs. Thus, cardiac muscle is a syncytium of many heart muscle cells in which the cardiac cells are so inter- CARDIAC MUSCLE ANATOMY connected that when one cell becomes excited, the action Figure 9-2 shows the cardiac muscle histology, demon- potential rapidly spreads to all of them. strating cardiac muscle fibers arranged in a latticework, The heart actually is composed of two syncytia; the with the fibers dividing, recombining, and then spreading atrial syncytium, which constitutes the walls of the two 113 UNIT III The Heart HEAD AND UPPER EXTREMITY Endocardial fibers Base Aorta Pulmonary artery Superior Lungs vena cava Right atrium Pulmonary Pulmonary veins valve Left atrium Mitral valve Epicardial fibers Apex Tricuspid valve Aortic valve A B Right ventricle Left Figure 9-3. A, The left ventricular inner subendocardial fibers (laven- ventricle der shade) run obliquely to the outer subepicardial fibers (red shade). Inferior vena cava B, The subepicardial muscle fibers are wrapped in a left-handed helix and subendocardial fibers are arranged in a right-handed helix. TRUNK AND Plateau LOWER EXTREMITY +20 0 Endocardium –20 Myocardium –40 –60 Epicardium –80 Pericardial space Millivolts Pericardium –100 Purkinje fiber Parietal pericardium Plateau Fibrous pericardium +20 Figure 9-1. Structure of the heart and course of blood flow through 0 the heart chambers and heart valves. The heart consists of multiple –20 layers, including the inner endocardium, myocardium, and more out- –40 ward epicardium and pericardium layers. –60 –80 –100 Ventricular muscle 0 1 2 3 4 Seconds Figure 9-4. Rhythmical action potentials (in millivolts) from a Purkin- je fiber and from a ventricular muscle fiber, recorded by microelec- trodes. Intercalated discs fibers several millimeters in diameter that is discussed in Chapter 10. This division of the muscle of the heart into two func- tional syncytia allows the atria to contract a short time ahead of ventricular contraction, which is important for the effectiveness of heart pumping. Figure 9-2. Syncytial interconnecting nature of cardiac muscle fibers. ACTION POTENTIALS IN CARDIAC MUSCLE atria; and the ventricular syncytium, which constitutes the walls of the two ventricles. The atria are separated The action potential recorded in a ventricular muscle from the ventricles by fibrous tissue that surrounds the fiber, shown in Figure 9-4, averages about 105 millivolts, atrioventricular (A-V) valvular openings between the which means that the intracellular potential rises from a atria and ventricles. Normally, potentials are not con- very negative value between beats, about −85 millivolts, ducted from the atrial syncytium into the ventricular to a slightly positive value, about +20 millivolts, during syncytium directly through this fibrous tissue. Instead, each beat. After the initial spike, the membrane remains they are only conducted by way of a specialized conduc- depolarized for about 0.2 second, exhibiting a plateau, fol- tive system called the A-V bundle, a bundle of conductive lowed at the end of the plateau by abrupt repolarization. 114  Chapter 9 Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves The presence of this plateau in the action potential causes ventricular contraction to last as much as 15 times longer 20 1 Membrane potential (millivolts) in cardiac muscle than in skeletal muscle. 2 0 What Causes the Long Action Potential and Plateau in UNIT III Cardiac Muscle? At least two major differences between -20 the membrane properties of cardiac and skeletal muscle ac- count for the prolonged action potential and the plateau in -40 0 3 cardiac muscle. First, the action potential of skeletal muscle is caused almost entirely by the sudden opening of large -60 numbers of fast sodium channels that allow tremendous -80 numbers of sodium ions to enter the skeletal muscle fiber 4 4 from the extracellular fluid. These channels are called fast -100 channels because they remain open for only a few thou- 0 100 200 300 sandths of a second and then abruptly close. At the end of Time (milliseconds) this closure, repolarization occurs, and the action potential is over within about another thousandth of a second. In cardiac muscle, the action potential is caused by Outward iK+ opening of two types of channels: (1) the same voltage- activated fast sodium channels as those in skeletal muscle; Ionic and (2) another entirely different population of L-type currents calcium channels (slow calcium channels), which are also Inward iCa2+ called calcium-sodium channels. This second population of channels differs from the fast sodium channels in that they are slower to open and, even more importantly, remain iNa+ open for several tenths of a second. During this time, a large quantity of both calcium and sodium ions flows through Figure 9-5. Phases of action potential of cardiac ventricular muscle these channels to the interior of the cardiac muscle fiber, cell and associated ionic currents for sodium (iNa+), calcium (iCa2+), and this activity maintains a prolonged period of depolar- and potassium (iK+). ization, causing the plateau in the action potential. Fur- thermore, the calcium ions that enter during this plateau Phase 0 (Depolarization): Fast Sodium Channels phase activate the muscle contractile process, whereas the Open. When the cardiac cell is stimulated and depolar- calcium ions that cause skeletal muscle contraction are izes, the membrane potential becomes more positive. derived from the intracellular sarcoplasmic reticulum. Voltage-gated sodium channels (fast sodium channels) The second major functional difference between car- open and permit sodium to rapidly flow into the cell and diac muscle and skeletal muscle that helps account for depolarize it. The membrane potential reaches about +20 both the prolonged action potential and its plateau is that millivolts before the sodium channels close. immediately after the onset of the action potential, the Phase 1 (Initial Repolarization): Fast Sodium Chan- permeability of the cardiac muscle membrane for potas- nels Close. The sodium channels close, the cell begins to sium ions decreases about fivefold, an effect that does not repolarize, and potassium ions leave the cell through open occur in skeletal muscle. This decreased potassium perme- potassium channels. ability may result from the excess calcium influx through Phase 2 (Plateau): Calcium Channels Open and Fast the calcium channels just noted. Regardless of the cause, Potassium Channels Close. A brief initial repolarization the decreased potassium permeability greatly decreases occurs and the action potential then plateaus as a result the efflux of positively charged potassium ions during the of increased calcium ion permeability and decreased po- action potential plateau and thereby prevents early return tassium ion permeability. The voltage-gated calcium ion of the action potential voltage to its resting level. When the channels open slowly during phases 1 and 0, and calcium slow calcium-sodium channels do close at the end of 0.2 enters the cell. Potassium channels then close, and the to 0.3 second, and the influx of calcium and sodium ions combination of decreased potassium ion efflux and in- ceases, the membrane permeability for potassium ions also creased calcium ion influx causes the action potential to increases rapidly. This rapid loss of potassium from the plateau. fiber immediately returns the membrane potential to its Phase 3 (Rapid Repolarization): Calcium Channels resting level, thus ending the action potential. Close and Slow Potassium Channels Open. The closure of calcium ion channels and increased potassium ion Phases of Cardiac Muscle Action Potential. Figure 9-5 permeability, permitting potassium ions to exit the cell summarizes the phases of the action potential in cardiac rapidly, ends the plateau and returns the cell membrane muscle and the ion flows that occur during each phase. potential to its resting level. 115 UNIT III The Heart Refractory period discussed for skeletal muscle in Chapter 7. Again, there Relative refractory are differences in this mechanism in cardiac muscle that have important effects on the characteristics of heart Force of contraction period Later premature contraction muscle contraction. Early premature contraction As is true for skeletal muscle, when an action poten- tial passes over the cardiac muscle membrane, the action potential spreads to the interior of the cardiac muscle fiber along the membranes of the transverse (T) tubules. The T tubule action potentials then act on the membranes of the longitudinal sarcoplasmic tubules to cause release of calcium ions into the muscle sarcoplasm from the sar- 0 1 2 3 coplasmic reticulum. In another few thousandths of a Seconds second, these calcium ions diffuse into the myofibrils and Figure 9-6. Force of ventricular heart muscle contraction, showing catalyze the chemical reactions that promote sliding of also the duration of the refractory period and relative refractory pe- riod, plus the effect of premature contraction. Note that premature the actin and myosin filaments along one another, which contractions do not cause wave summation, as occurs in skeletal produces the muscle contraction. muscle. Thus far, this mechanism of excitation-contraction coupling is the same as that for skeletal muscle, but there Phase 4 (Resting Membrane Potential):. This averages is a second effect that is quite different. In addition to about−80 to −90 millivolts. the calcium ions that are released into the sarcoplasm from the cisternae of the sarcoplasmic reticulum, cal- Velocity of Signal Conduction in Cardiac Muscle. The cium ions also diffuse into the sarcoplasm from the T velocity of conduction of the excitatory action potential tubules at the time of the action potential, which opens signal along both atrial and ventricular muscle fibers is voltage-dependent calcium channels in the membrane of about 0.3 to 0.5 m/sec, or about 1/250 the velocity in very the T tubule (Figure 9-7). Calcium entering the cell then large nerve fibers and about 1/10 the velocity in skeletal activates calcium release channels, also called ryanodine muscle fibers. The velocity of conduction in the special- receptor channels, in the sarcoplasmic reticulum mem- ized heart conductive system—in the Purkinje fibers—is brane, triggering the release of calcium into the sarco- as high as 4 m/sec in most parts of the system, allowing plasm. Calcium ions in the sarcoplasm then interact with rapid conduction of the excitatory signal to the different troponin to initiate cross-bridge formation and contrac- parts of the heart, as explained in Chapter 10. tion by the same basic mechanism as that described for skeletal muscle in Chapter 6. Refractory Period of Cardiac Muscle. Cardiac muscle, Without the calcium from the T tubules, the like all excitable tissue, is refractory to restimulation dur- strength of cardiac muscle contraction would be ing the action potential. Therefore, the refractory period reduced considerably because the sarcoplasmic reticu- of the heart is the interval of time, as shown to the left in lum of cardiac muscle is less well developed than that Figure 9-6, during which a normal cardiac impulse can- of skeletal muscle and does not store enough calcium not re-excite an already excited area of cardiac muscle. to provide full contraction. The T tubules of cardiac The normal refractory period of the ventricle is 0.25 to muscle, however, have a diameter five times as great 0.30 second, which is about the duration of the prolonged as that of the skeletal muscle tubules, which means a plateau action potential. There is an additional relative volume 25 times as great. Also, inside the T tubules is refractory period of about 0.05 second during which the a large quantity of mucopolysaccharides that are elec- muscle is more difficult to excite than normal but can be tronegatively charged and bind an abundant store of excited by a very strong excitatory signal, as demonstrated calcium ions, keeping them available for diffusion to by the early premature contraction in the second example the interior of the cardiac muscle fiber when a T tubule of Figure 9-6. The refractory period of atrial muscle is action potential appears. much shorter than that for the ventricles (about 0.15 sec- The strength of contraction of cardiac muscle depends ond for the atria compared with 0.25 to 0.30 second for to a great extent on the concentration of calcium ions in the ventricles). the extracellular fluids. In fact, a heart placed in a calcium- free solution will quickly stop beating. The reason for this response is that the openings of the T tubules pass directly EXCITATION-CONTRACTION COUPLING— through the cardiac muscle cell membrane into the extra- FUNCTION OF CALCIUM IONS AND THE cellular spaces surrounding the cells, allowing the same TRANSVERSE TUBULES extracellular fluid that is in the cardiac muscle intersti- The term excitation-contraction coupling refers to the tium to percolate through the T tubules. Consequently, mechanism whereby the action potential causes the the quantity of calcium ions in the T tubule system (i.e., myofibrils of muscle to contract. This mechanism was the availability of calcium ions to cause cardiac muscle 116  Chapter 9 Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves Extracellular fluid Ca2+ Ca2+ Na+ K+ Sarcolemma UNIT III ATP Ca2+ Na+ Cytoplasm Sarcoplasmic Sarcoplasmic reticulum L-type reticulum Ca2+ Ca2+ channel Ca2+ RyR stores Ca2+ T Tubule ATP spark Ca2+ SERCA2 Ca2+ signal Ca2+ Contraction relaxation Figure 9-7. Mechanisms of excitation-contraction coupling and relaxation in cardiac muscle. ATP, Adenosine triphosphate. RyR, ryanodine receptor Ca2+ release channel; SERCA, sarcoplasmic reticulum Ca2+-ATPase contraction) depends to a great extent on the extracellular and continues to contract until a few milliseconds af- fluid calcium ion concentration. ter the action potential ends. Therefore, the duration of In contrast, the strength of skeletal muscle contrac- contraction of cardiac muscle is mainly a function of the tion is hardly affected by moderate changes in extracel- duration of the action potential, including the plateau— lular fluid calcium concentration. This is because skeletal about 0.2 second in atrial muscle and 0.3 second in ven- muscle contraction is caused almost entirely by calcium tricular muscle. ions released from the sarcoplasmic reticulum inside the skeletal muscle fiber. CARDIAC CYCLE At the end of the plateau of the cardiac action poten- tial, the influx of calcium ions to the interior of the muscle The cardiac events that occur from the beginning of fiber is suddenly cut off, and calcium ions in the sarco- one heartbeat to the beginning of the next are called the plasm are rapidly pumped back out of the muscle fibers cardiac cycle. Each cycle is initiated by the spontane- into the sarcoplasmic reticulum and T tubule–extra- ous generation of an action potential in the sinus node, cellular fluid space. Transport of calcium back into the as explained in Chapter 10. This node is located in the sarcoplasmic reticulum is achieved with the help of a superior lateral wall of the right atrium near the open- calcium–adenosine triphosphatase (ATPase) pump (the ing of the superior vena cava, and the action potential sarcoplasmic endoplasmic reticulum calcium ATPase, travels from here rapidly through both atria and then SERCA2; see Figure 9-7). Calcium ions are also removed through the A-V bundle into the ventricles. Because of from the cell by a sodium-calcium exchanger. The sodium this special arrangement of the conducting system from that enters the cell during this exchange is then trans- the atria into the ventricles, there is a delay of more than ported out of the cell by the sodium-potassium ATPase 0.1 second during passage of the cardiac impulse from pump. As a result, the contraction ceases until a new the atria into the ventricles. This delay allows the atria action potential comes along. to contract ahead of ventricular contraction, thereby pumping blood into the ventricles before the strong ven- Duration of Contraction. Cardiac muscle begins to con- tricular contraction begins. Thus, the atria act as primer tract a few milliseconds after the action potential begins pumps for the ventricles, and the ventricles in turn 117 UNIT III The Heart Isovolumic relaxation Rapid inflow Atrial systole Isovolumic Ejection Diastasis contraction 120 Aortic Aortic valve valve closes 100 Pressure (mm Hg) opens Aortic pressure 80 60 A-V valve A-V valve 40 closes opens 20 Atrial pressure a c v 0 Ventricular pressure Volume (ml) 130 Ventricular volume 90 R Figure 9-8. Events of the cardiac 50 P cycle for left ventricular function, T Electrocardiogram showing changes in left atrial pres- Q 1st 2nd 3rd S sure, left ventricular pressure, aortic pressure, ventricular volume, the Phonocardiogram electrocardiogram, and the phono- cardiogram. A-V, Atrioventricular. Systole Diastole Systole provide the major source of power for moving blood Relationship of the Electrocardiogram to through the body’s vascular system. the Cardiac Cycle The electrocardiogram in Figure 9-8 shows the P, Q, R, S, Diastole and Systole and T waves, discussed in Chapters 11 and 12. These are The total duration of the cardiac cycle, including systole electrical voltages generated by the heart and recorded and diastole, is the reciprocal of the heart rate. For exam- by the electrocardiogram from the surface of the body. ple, if the heart rate is 72 beats/min, the duration of the The P wave is caused by the spread of depolarization cardiac cycle is 1/72 min/beat—about 0.0139 min/beat, or through the atria and is followed by atrial contraction, 0.833 sec/beat. which causes a slight rise in the atrial pressure curve Figure 9-8 shows the different events during the car- immediately after the electrocardiographic P wave. diac cycle for the left side of the heart. The top three About 0.16 second after the onset of the P wave, the curves show the pressure changes in the aorta, left ventri- QRS waves appear as a result of electrical depolarization cle, and left atrium, respectively. The fourth curve depicts of the ventricles, which initiates contraction of the ven- the changes in left ventricular volume, the fifth depicts tricles and causes the ventricular pressure to begin ris- the electrocardiogram, and the sixth depicts a phonocar- ing. Therefore, the QRS complex begins slightly before the diogram, which is a recording of the sounds produced by onset of ventricular systole. the heart—mainly by the heart valves—as it pumps. It is Finally, the ventricular T wave represents the stage especially important that the reader study this figure in of repolarization of the ventricles when the ventricular detail and understand the causes of all the events shown. muscle fibers begin to relax. Therefore, the T wave occurs slightly before the end of ventricular contraction. Increasing Heart Rate Decreases Duration of Cardiac Cycle. When heart rate increases, the duration of each The Atria Function as Primer Pumps for cardiac cycle decreases, including the contraction and the Ventricles relaxation phases. The duration of the action potential Blood normally flows continually from the great veins and systole also decrease, but not by as great a percent- into the atria; about 80% of the blood flows directly age as diastole. At a normal heart rate of 72 beats/min, through the atria into the ventricles, even before the systole comprises about 0.4 of the entire cardiac cycle. At atria contract. Then, atrial contraction usually causes three times the normal heart rate, systole is about 0.65 of an additional 20% filling of the ventricles. Therefore, the the entire cardiac cycle. This means that the heart beat- atria function as primer pumps that increase the ventric- ing very rapidly does not remain relaxed long enough to ular pumping effectiveness as much as 20%. However, allow complete filling of the cardiac chambers before the the heart can continue to operate under most condi- next contraction. tions even without this extra 20% effectiveness because 118  Chapter 9 Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves it normally has the capability of pumping 300% to 400% Outflow of Blood from the Ventricles more blood than is required by the resting body. There- During Systole fore, when the atria fail to function, the difference is Period of Isovolumic (Isometric) Contraction. Immedi- unlikely to be noticed unless a person exercises; then, ately after ventricular contraction begins, the ventricular symptoms of heart failure occasionally develop, espe- pressure rises abruptly, as shown in Figure 9-8, causing UNIT III cially shortness of breath. the A-V valves to close. Then, an additional 0.02 to 0.03 second is required for the ventricle to build up sufficient Pressure Changes in the Atria—a, c, and v Waves. In the pressure to push the semilunar (aortic and pulmonary) atrial pressure curve of Figure 9-8, three minor pressure el- valves open against the pressures in the aorta and pulmo- evations, called a, c, and v atrial pressure waves, are shown. nary artery. Therefore, during this period, contraction is The a wave is caused by atrial contraction. Ordinarily, occurring in the ventricles, but no emptying occurs. This the right atrial pressure increases 4 to 6 mm Hg during atri- al contraction, and the left atrial pressure increases about 7 period is called the period of isovolumic or isometric con- to 8 mm Hg. traction, meaning that cardiac muscle tension is increas- The c wave occurs when the ventricles begin to contract; ing but little or no shortening of the muscle fibers is oc- it is caused partly by slight backflow of blood into the atria curring. at the onset of ventricular contraction, but mainly by bulg- ing of the A-V valves backward toward the atria because of Period of Ejection. When the left ventricular pressure increasing pressure in the ventricles. rises slightly above 80 mm Hg (and the right ventricular The v wave occurs toward the end of ventricular con- pressure rises slightly above 8 mm Hg), the ventricular traction; it results from slow flow of blood into the atria pressures push the semilunar valves open. Immediately, from the veins while the A-V valves are closed during ven- blood is ejected out of the ventricles into the aorta and tricular contraction. Then, when ventricular contraction is pulmonary artery. Approximately 60% of the blood in the over, the A-V valves open, allowing this stored atrial blood to flow rapidly into the ventricles, causing the v wave to ventricles at the end of diastole is ejected during systole; disappear. about 70% of this portion flows out during the first third of the ejection period, with the remaining 30% emptying during the next two thirds. Therefore, the first third is called the period of rapid ejection, and the last two thirds FUNCTION OF THE VENTRICLES AS PUMPS is called the period of slow ejection. The Ventricles Fill with Blood During Diastole. During ventricular systole, large amounts of blood Period of Isovolumic (Isometric) Relaxation. At the accumulate in the right and left atria because of the end of systole, ventricular relaxation begins suddenly, al- closed A-V valves. Therefore, as soon as systole is lowing both the right and left intraventricular pressures to over, and the ventricular pressures fall again to their decrease rapidly. The elevated pressures in the distended low diastolic values, the moderately increased pres- large arteries that have just been filled with blood from sures that have developed in the atria during ven- the contracted ventricles immediately push blood back tricular systole immediately push the A-V valves open toward the ventricles, which snaps the aortic and pulmo- and allow blood to flow rapidly into the ventricles, as nary valves closed. For another 0.03 to 0.06 second, the shown by the rise of the left ventricular volume curve ventricular muscle continues to relax, even though the in Figure 9-8. This period is called the period of rapid ventricular volume does not change, giving rise to the pe- filling of the ventricles. riod of isovolumic or isometric relaxation. During this pe- In a healthy heart, the period of rapid filling lasts for riod, the intraventricular pressures rapidly decrease back about the first third of diastole. During the middle third of to their low diastolic levels. Then, the A-V valves open to diastole, only a small amount of blood normally flows into begin a new cycle of ventricular pumping. the ventricles. This is blood that continues to empty into the atria from the veins and passes through the atria directly End-Diastolic Volume, End-Systolic Volume, and into the ventricles. During the last third of diastole, the atria Stroke Volume Output. During diastole, normal filling contract and give an additional thrust to the inflow of blood of the ventricles increases the volume of each ventricle into the ventricles. This mechanism accounts for about 20% to about 110 to 120 ml. This volume is called the end- of the filling of the ventricles during each heart cycle. diastolic volume. Then, as the ventricles empty during sys- The ventricles stiffen with aging or diseases that tole, the volume decreases by about 70 ml, which is called cause cardiac fibrosis such as high blood pressure or the stroke volume output. The remaining volume in each diabetes mellitus. This causes less blood to fill the ventricle, about 40 to 50 ml, is called the end-systolic vol- ventricles in the early portion of diastole and requires ume. The fraction of the end-diastolic volume that is eject- more volume (preload; discussed later) or more filling ed is called the ejection fraction, usually equal to about 0.6 from the later atrial contraction to maintain adequate (or 60%). The ejection fraction percentage is often used cardiac output. clinically to assess cardiac systolic (pumping) capability. 119 UNIT III The Heart flow from a myocardial infarction, the valve bulges far backward during ventricular contraction, sometimes so MITRAL VALVE far that it leaks severely and results in severe or even lethal cardiac incapacity. Cusp Aortic and Pulmonary Artery Valves. The aortic and pulmonary artery semilunar valves function quite dif- Chordae tendineae ferently from the A-V valves. First, the high pressures in the arteries at the end of systole cause the semilunar Papillary muscles valves to snap closed, in contrast to the much softer closure of the A-V valves. Second, because of smaller openings, the velocity of blood ejection through the Cusp aortic and pulmonary valves is much greater than that through the much larger A-V valves. Also, because of the rapid closure and rapid ejection, the edges of the AORTIC VALVE aortic and pulmonary valves are subjected to much greater mechanical abrasion than the A-V valves. Fi- nally, the A-V valves are supported by the chordae Figure 9-9. Mitral and aortic valves (the left ventricular valves). tendineae, which is not true for the semilunar valves. It is obvious from the anatomy of the aortic and pul- When the heart contracts strongly, the end-systolic monary valves (as shown for the aortic valve at the bot- volume may decrease to as little as 10 to 20 ml. Con- tom of Figure 9-9) that they must be constructed with versely, when large amounts of blood flow into the ventri- an especially strong, yet very pliable, fibrous tissue to cles during diastole, the ventricular end-diastolic volumes withstand the extra physical stresses. can become as much as 150 to 180 ml in the healthy heart. By both increasing the end-diastolic volume and decreas- AORTIC PRESSURE CURVE ing the end-systolic volume, the stroke volume output can be increased to more than double that which is normal. When the left ventricle contracts, the ventricular pressure increases rapidly until the aortic valve opens. Then, after the valve opens, the pressure in the ventricle rises much THE HEART VALVES PREVENT BACKFLOW less rapidly, as shown in Figure 9-7, because blood imme- OF BLOOD DURING SYSTOLE diately flows out of the ventricle into the aorta and then Atrioventricular Valves. The A-V valves (i.e., the tricus- into the systemic distribution arteries. pid and mitral valves) prevent backflow of blood from The entry of blood into the arteries during systole the ventricles to the atria during systole, and the semilu- causes the walls of these arteries to stretch and the pres- nar valves (i.e., the aortic and pulmonary artery valves) sure to increase to about 120 mm Hg. Next, at the end prevent backflow from the aorta and pulmonary arteries of systole, after the left ventricle stops ejecting blood into the ventricles during diastole. These valves, shown in and the aortic valve closes, the elastic walls of the arter- Figure 9-9 for the left ventricle, close and open passively. ies maintain a high pressure in the arteries, even during That is, they close when a backward pressure gradient diastole. pushes blood backward, and they open when a forward An incisura occurs in the aortic pressure curve when pressure gradient forces blood in the forward direction. the aortic valve closes. This is caused by a short period of For anatomical reasons, the thin A-V valves require al- backward flow of blood immediately before closure of the most no backflow to cause closure, whereas the much valve, followed by the sudden cessation of backflow. heavier semilunar valves require rather rapid backflow for After the aortic valve closes, pressure in the aorta a few milliseconds. decreases slowly throughout diastole because the blood stored in the distended elastic arteries flows continually Function of the Papillary Muscles. Figure 9-9 also through the peripheral vessels back to the veins. Before shows papillary muscles that attach to the vanes of the the ventricle contracts again, the aortic pressure usually A-V valves by the chordae tendineae. The papillary mus- has fallen to about 80 mm Hg (diastolic pressure), which cles contract when the ventricular walls contract but, is two thirds the maximal pressure of 120 mm Hg (sys- contrary to what might be expected, they do not help the tolic pressure) that occurs in the aorta during ventricular valves to close. Instead, they pull the vanes of the valves contraction. inward toward the ventricles to prevent their bulging too The pressure curves in the right ventricle and pulmo- far backward toward the atria during ventricular contrac- nary artery are similar to those in the aorta, except that tion. If a chorda tendina becomes ruptured, or if one of the pressures are only about one-sixth as great, as dis- the papillary muscles becomes paralyzed due to low blood cussed in Chapter 14. 120  Chapter 9 Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves Relationship of the Heart Sounds to Heart Pumping 300 Left intraventricular pressure (mm Hg) Systolic pressure When listening to the heart with a stethoscope, one does not hear the opening of the valves because this is a relatively slow 250 process that normally makes no noise. However, when the 200 Isovolumic valves close, the vanes of the valves and the surrounding fluids relaxation UNIT III vibrate under the influence of sudden pressure changes, giving Period of ejection off sound that travels in all directions through the chest. 150 When the ventricles contract, one first hears a sound III Isovolumic caused by closure of the A-V valves. The vibration pitch is 100 contraction low and relatively long-lasting and is known as the first heart EW sound (S1). When the aortic and pulmonary valves close at 50 IV II Diastolic the end of systole, one hears a rapid snap because these valves PE pressure I close rapidly, and the surroundings vibrate for a short period. 0 This sound is called the second heart sound (S2). The precise 0 50 100 150 200 250 causes of the heart sounds are discussed more fully in Chapter Period of filling Left ventricular volume (ml) 23 in relation to listening to the sounds with the stethoscope. Figure 9-10. Relationship between left ventricular volume and intra- Work Output of the Heart ventricular pressure during diastole and systole. Also shown by the red lines is the “volume-pressure diagram,” demonstrating changes The stroke work output of the heart is the amount of energy in intraventricular volume and pressure during the normal cardiac cy- that the heart converts to work during each heartbeat while cle. EW, Net external work; PE, potential energy. pumping blood into the arteries. Work output of the heart is in two forms. First, the major proportion is used to move Until the volume of the noncontracting ventricle the blood from the low-pressure veins to the high-pressure arteries. This is called volume-pressure work or external rises above about 150 ml, the diastolic pressure does work. Second, a minor proportion of the energy is used to not increase much. Therefore, up to this volume, blood accelerate the blood to its velocity of ejection through the can flow easily into the ventricle from the atrium. Above aortic and pulmonary valves, which is the kinetic energy of 150 ml, the ventricular diastolic pressure increases rap- blood flow component of the work output. idly, partly because of fibrous tissue in the heart that will Right ventricular external work output is normally stretch no more, and partly because the pericardium that about one-sixth the work output of the left ventricle be- surrounds the heart becomes filled nearly to its limit. cause of the sixfold difference in systolic pressures pumped During ventricular contraction, the systolic pressure by the two ventricles. The additional work output of each increases, even at low ventricular volumes, and reaches a ventricle required to create kinetic energy of blood flow is maximum at a ventricular volume of 150 to 170 ml. Then, proportional to the mass of blood ejected times the square as the volume increases further, the systolic pressure actu- of velocity of ejection. Ordinarily, the work output of the left ventricle required ally decreases under some conditions, as demonstrated to create kinetic energy of blood flow is only about 1% of by the falling systolic pressure curve in Figure 9-10. This the total work output of the ventricle and therefore is ig- occurs because at these great volumes, the actin and myo- nored in the calculation of the total stroke work output. In sin filaments of the cardiac muscle fibers are pulled apart certain abnormal conditions, however, such as aortic ste- far enough that the strength of each cardiac fiber contrac- nosis, in which blood flows with great velocity through the tion becomes less than optimal. stenosed valve, more than 50% of the total work output may Note especially in the figure that the maximum sys- be required to create kinetic energy of blood flow. tolic pressure for the normal left ventricle is between 250 and 300 mm Hg, but this varies widely with each person’s heart strength and degree of heart stimulation by cardiac GRAPHIC ANALYSIS OF VENTRICULAR nerves. For the normal right ventricle, the maximum sys- PUMPING tolic pressure is between 60 and 80 mm Hg. Figure 9-10 shows a diagram that is especially useful in explaining the pumping mechanics of the left ventricle. Volume-Pressure Diagram During the Cardiac Cycle; The most important components of the diagram are the Cardiac Work Output. The red lines in Figure 9-10 form two curves labeled “diastolic pressure” and “systolic pres- a loop called the volume-pressure diagram of the cardiac sure.” These curves are volume-pressure curves. cycle for normal function of the left ventricle. A more de- The diastolic pressure curve is determined by filling tailed version of this loop is shown in Figure 9-11. It is the heart with progressively greater volumes of blood and divided into four phases. then measuring the diastolic pressure immediately before Phase I: Period of Filling. Phase I in the volume- ventricular contraction occurs, which is the end-diastolic pressure diagram begins at a ventricular volume of about pressure of the ventricle. 50 ml and a diastolic pressure of 2 to 3 mm Hg. The The systolic pressure curve is determined by recording amount of blood that remains in the ventricle after the the systolic pressure achieved during ventricular contrac- previous heartbeat, 50 ml, is called the end-systolic vol- tion at each volume of filling. ume. As venous blood flows into the ventricle from the 121 UNIT III The Heart Period of ejection 120 Aortic valve 100 closes D Left intraventricular pressure (mm Hg) EW Aortic valve 80 opens C Isovolumetric relaxation 60 Stroke volume Isovolumetric contraction 40 20 End-systolic End-diastolic Figure 9-11. The volume-pressure diagram dem- volume Period of volume B onstrating changes in intraventricular volume and Mitral valve filling Mitral valve opens A pressure during a single cardiac cycle (red line). closes The shaded area represents the net external work 0 (EW) output by the left ventricle during the cardiac 0 50 70 90 110 130 cycle. Left ventricular volume (ml) left atrium, the ventricular volume normally increases to contraction, this diagram is used for calculating cardiac about 120 ml, called the end-diastolic volume, an increase work output. of 70 ml. Therefore, the volume-pressure diagram during When the heart pumps large quantities of blood, the phase I extends along the line in Figure 9-10 labeled “I” area of the work diagram becomes much larger. That is, and from point A to point B in Figure 9-11, with the vol- it extends far to the right because the ventricle fills with ume increasing to 120 ml and the diastolic pressure rising more blood during diastole, it rises much higher because to about 5 to 7 mm Hg. the ventricle contracts with greater pressure, and it usu- Phase II: Period of Isovolumic Contraction. During ally extends farther to the left because the ventricle con- isovolumic contraction, the volume of the ventricle does tracts to a smaller volume—especially if the ventricle is not change because all valves are closed. However, the stimulated to increased activity by the sympathetic ner- pressure inside the ventricle increases to equal the pres- vous system. sure in the aorta, at a pressure value of about 80 mm Hg, as depicted by point C (see Figure 9-11). Concepts of Preload and Afterload. In assessing the Phase III: Period of Ejection. During ejection, the contractile properties of muscle, it is important to specify systolic pressure rises even higher because of still more the degree of tension on the muscle when it begins to con- contraction of the ventricle. At the same time, the volume tract, called the preload, and to specify the load against of the ventricle decreases because the aortic valve has which the muscle exerts its contractile force, called the now opened, and blood flows out of the ventricle into the afterload. aorta. Therefore, in Figure 9-10, the curve labeled “III,” For cardiac contraction, the preload is usually con- or “period of ejection,” traces the changes in volume and sidered to be the end-diastolic pressure when the ven- systolic pressure during this period of ejection. tricle has become filled. The afterload of the ventricle Phase IV: Period of Isovolumic Relaxation. At the end is the pressure in the aorta leading from the ventricle. of the period of ejection (point D, Figure 9-11), the aortic In Figure 9-10, this corresponds to the systolic pressure valve closes, and the ventricular pressure falls back to the described by the phase III curve of the volume-pressure diastolic pressure level. The line labeled “IV” (Figure 9- diagram. (Sometimes the afterload is loosely considered 10) traces this decrease in intraventricular pressure with- to be the resistance in the circulation rather than the out any change in volume. Thus, the ventricle returns to pressure.) its starting point, with about 50 ml of blood left in the The importance of the concepts of preload and after- ventricle at an atrial pressure of 2 to 3 mm Hg. load is that in many abnormal functional states of the The area subtended by this functional volume- heart or circulation, the pressure during filling of the ven- pressure diagram (the shaded area, labeled “EW”) repre- tricle (the preload), the arterial pressure against which the sents the net external work output of the ventricle during ventricle must contract (the afterload), or both are altered its contraction cycle. In experimental studies of cardiac from normal to a severe degree. 122  Chapter 9 Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves Chemical Energy Required for Cardiac Contraction: (2) control of heart rate and heart strength by the auto- Oxygen Utilization by the Heart nomic nervous system. Heart muscle, like skeletal muscle, uses chemical energy to provide the work of contraction. Approximately 70% to 90% of this energy is normally derived from oxidative INTRINSIC REGULATION OF HEART PUMPING—THE FRANK-STARLING UNIT III metabolism of fatty acids, with about 10% to 30% com- ing from other nutrients, especially glucose and lactate. MECHANISM Therefore, the rate of oxygen consumption by the heart In Chapter 20, we will learn that under most conditions, is an excellent measure of the chemical energy liberated the amount of blood pumped by the heart each minute is while the heart performs its work. The different chemi- normally determined almost entirely by the rate of blood cal reactions that liberate this energy are discussed in Chapters 68 and 69. flow into the heart from the veins, which is called venous Experimental studies have shown that oxygen consump- return. That is, each peripheral tissue of the body controls tion of the heart and the chemical energy expended during its own local blood flow, and all the local tissue flows com- contraction are directly related to the total shaded area in bine and return by way of the veins to the right atrium. Figure 9-10. This shaded portion consists of the external The heart, in turn, automatically pumps this incoming work (EW), as explained earlier, and an additional portion blood into the arteries so that it can flow around the cir- called the potential energy, labeled “PE.” The potential ener- cuit again. gy represents additional work that could be accomplished by This intrinsic ability of the heart to adapt to increasing contraction of the ventricle if the ventricle could completely volumes of inflowing blood is called the Frank-Starling empty all the blood in its chamber with each contraction. mechanism of the heart, named in honor of Otto Frank Oxygen consumption has also been shown to be nearly and Ernest Starling, two great physiologists. Basically, the proportional to the tension that occurs in the heart mus- cle during contraction multiplied by the duration of time Frank-Starling mechanism means that the more the heart that the contraction persists; this is called the tension-time muscle is stretched during filling, the greater is the force index. According to the law of Laplace, ventricular wall ten- of contraction, and the greater is the quantity of blood sion (T) is related to the left ventricular pressure (P) and the pumped into the aorta. Or, stated another way—within radius (r): T = P × r. physiological limits, the heart pumps all the blood that Because tension is high when systolic pressure (and returns to it by way of the veins. therefore left ventricular pressure) is high, correspondingly more oxygen is used. When systolic pressure is chroni- What Is the Explanation of the Frank-Starling Mech- cally elevated, wall stress and cardiac workload are also in- anism? When an extra amount of blood flows into the creased, inducing thickening of the left ventricular walls, ventricles, the cardiac muscle is stretched to a greater which can reduce the ventricular chamber radius (concen- length. This stretching causes the muscle to contract with tric hypertrophy) and at least partially relieve the increased wall tension. Also, much more chemical energy is expend- increased force because the actin and myosin filaments ed, even at normal systolic pressures, when the ventricle are brought to a more nearly optimal degree of overlap is abnormally dilated (eccentric hypertrophy) because the for force generation. Therefore, the ventricle, because of heart muscle tension during contraction is proportional to its increased pumping, automatically pumps the extra pressure times the radius of the ventricle. This becomes es- blood into the arteries. This ability of stretched muscle, pecially important in heart failure when the heart ventricle up to an optimal length, to contract with increased work is dilated and, paradoxically, the amount of chemical en- output is characteristic of all striated muscle, as explained ergy required for a given amount of work output is greater in Chapter 6, and is not simply a characteristic of cardiac than normal, even though the heart is already failing. muscle. Cardiac Efficiency. During heart muscle contraction, In addition to the important effect of lengthening the most of the expended chemical energy is converted into heat, heart muscle, another factor increases heart pumping and a much smaller portion is converted into work output. when its volume is increased. Stretch of the right atrial Cardiac efficiency is the ratio of work output to total chemi- cal energy used to perform the work. Maximum efficiency of wall directly increases the heart rate by 10% to 20%, which the normal heart is between 20% and 25%. In persons with also helps increase the amount of blood pumped each heart failure, this efficiency can decrease to as low as 5%. minute, although its contribution is much less than that of the Frank-Starling mechanism. As discussed in Chapter 18, stretch of the atrium also activates stretch receptors and a nervous reflex, the Bainbridge reflex, that is trans- REGULATION OF HEART PUMPING mitted by the vagus nerve and may increase heart rate an When a person is at rest, the heart pumps only 4 to 6 additional 40% to 60%. liters of blood each minute. During strenuous exercise, the heart may pump four to seven times this amount. The Ventricular Function Curves basic mechanisms for regulating heart pumping are as fol- One of the best ways to express the functional ability of lows: (1) intrinsic cardiac pumping regulation in response the ventricles to pump blood is by ventricular function to changes in volume of blood flowing into the heart; and curves. Figure 9-12 shows a type of ventricular function 123 UNIT III The Heart Left ventricular Right ventricular Vagi stroke work stroke work (gram-meters) (gram-meters) 40 4 30 3 Sympathetic 20 2 chain 10 1 S-A node A-V 0 0 node 0 10 20 0 10 20 Left mean atrial Right mean atrial pressure pressure (mm Hg) (mm Hg) Figure 9-12. Left and right ventricular function curves recorded from dogs, depicting ventricular stroke work output as a function of left and right mean atrial pressures. (Data from Sarnoff SJ: Myocardial contractility as described by ventricular function curves. Physiol Rev 35:107, 1955.) Sympathetic nerves 15 Ventricular output (L/min) Right ventricle Figure 9-14. Cardiac sympathetic and parasympathetic nerves. (The vagus nerves to the heart are parasympathetic nerves.) A-V, Atrioven- 10 tricular; S-A, sinoatrial. Left ventricle increased more than 100% by sympathetic stimulation. By 5 contrast, the output can be decreased to almost zero by vagal (parasympathetic) stimulation. 0 –4 0 +4 +8 +12 +16 Mechanisms of Excitation of the Heart by the Sym- Atrial pressure (mm Hg) pathetic Nerves. Strong sympathetic stimulation can increase the heart rate in young adult humans from the Figure 9-13. Approximate normal right and left ventricular volume output curves for the normal resting human heart as extrapolated normal rate of 70 beats/min up to 180 to 200 beats/min from data obtained in dogs and data from humans. and, rarely, even 250 beats/min. Also, sympathetic stimu- lation may double the force of heart contraction, thereby curve called the stroke work output curve. Note that as increasing the volume of blood pumped and increasing the atrial pressure for each side of the heart increases, stroke ejection pressure. Thus, sympathetic stimulation often can work output for that side increases until it reaches the increase the maximum cardiac output as much as twofold limit of the ventricle’s pumping ability. to threefold, in addition to the increased output caused by Figure 9-13 shows another type of ventricular func- the Frank-Starling mechanism already discussed. tion curve called the ventricular volume output curve. The Conversely, inhibition of the sympathetic nerves to the two curves of this figure represent function of the two heart can decrease cardiac pumping to a moderate extent. ventricles of the human heart based on data extrapolated Under normal conditions, the sympathetic nerve fibers from experimental animal studies. As the right and left to the heart discharge continuously at a slow rate that atrial pressures increase, the respective ventricular vol- maintains pumping at about 30% above that with no sym- ume outputs per minute also increase. pathetic stimulation. Therefore, when sympathetic ner- Thus, ventricular function curves are another way of vous system activity is depressed below normal, both the expressing the Frank-Starling mechanism of the heart. heart rate and strength of ventricular muscle contraction That is, as the ventricles fill in response to higher atrial decrease, thereby decreasing the level of cardiac pumping pressures, each ventricular volume and strength of car- by as much as 30% below normal. diac muscle contraction increase, causing the heart to pump increased quantities of blood into the arteries. Parasympathetic (Vagal) Stimulation Reduces Heart Rate and Strength of Contraction. Strong stimulation Control of the Heart by the Sympathetic of the parasympathetic nerve fibers in the vagus nerves and Parasympathetic Nerves to the heart can stop the heartbeat for a few seconds, but The pumping effectiveness of the heart also is controlled then the heart usually “escapes” and beats at a rate of 20 by the sympathetic and parasympathetic (vagus) nerves, to 40 beats/min as long as the parasympathetic stimula- which abundantly supply the heart, as shown in Figure tion continues. In addition, strong vagal stimulation can 9-14. For given levels of atrial pressure, the amount of decrease the strength of heart muscle contraction by 20% blood pumped each minute (cardiac output) often can be to 30%. 124  Chapter 9 Cardiac Muscle: The Heart as a Pump and Function of the Heart Valves 25 Maximum sympathetic ions in the extracellular fluids have important effects on stimulation cardiac pumping. Effect of Potassium Ions. Excess potassium in the ex- 20 tracellular fluids causes the heart to become dilated and UNIT III flaccid and also slows the heart rate. Large quantities of Cardiac output (L/min) Normal sympathetic potassium also can block conduction of the cardiac im- 15 stimulation pulse from the atria to the ventricles through the A-V bundle. Elevation of potassium concentration to only 8 Zero sympathetic to 12 mEq/L—two to three times the normal value—can 10 stimulation cause severe weakness of the heart, abnormal rhythm, (Parasympathetic and death. stimulation) These effects result partially from the fact that a 5 high potassium concentration in the extracellular fluids decreases the resting membrane potential in the car- diac muscle fibers, as explained in Chapter 5. That is, a 0 –4 0 +4 +8 high extracellular fluid potassium concentration partially Right atrial pressure (mm Hg) depolarizes the cell membrane, causing the membrane potential to be less negative. As the membrane poten- Figure 9-15. Effect on the cardiac output curve of different degrees of sympathetic or parasympathetic stimulation. tial decreases, the intensity of the action potential also decreases, which makes contraction of the heart progres- sively weaker. The vagal fibers are distributed mainly to the atria and not much to the ventricles, where the power contrac- Effect of Calcium Ions. Excess calcium ions cause effects tion of the heart occurs. This distribution explains why almost exactly opposite to those of potassium ions, caus- the effect of vagal stimulation is mainly to decrease the ing the heart to move toward spastic contraction. This ef- heart rate rather than to decrease greatly the strength fect is caused by a direct effect of calcium ions to initiate of heart contraction. Nevertheless, the great decrease in the cardiac contractile process, as explained earlier in this heart rate, combined with a slight decrease in heart con- chapter. traction strength, can decrease ventricular pumping by Conversely, deficiency of calcium ions causes cardiac 50% or more. weakness, similar to the effect of high potassium. For- tunately, calcium ion levels in the blood normally are Effect of Sympathetic or Parasympathetic Stimula- regulated within a very narrow range. Therefore, cardiac tion on the Cardiac Function Curve. Figure 9-15 shows effects of abnormal calcium concentrations are seldom of four cardiac function curves. These curves are similar to clinical concern. the ventricular function curves of Figure 9-13. However, they represent function of the entire heart rather than EFFECT OF TEMPERATURE ON HEART that of a single ventricle. They show the relationship be- FUNCTION tween right atrial pressure at the input of the right heart and cardiac output from the left ventricle into the aorta. Increased body temperature, such as that which occurs The curves of Figure 9-15 demonstrate that at any during fever, greatly increases the heart rate, sometimes given right atrial pressure, the cardiac output increases to double the normal rate. Decreased temperature greatly during increased sympathetic stimulation and decreases decreases the heart rate, which may fall to as low as a during increased parasympathetic stimulation. These few beats per minute when a person is near death from changes in output caused by autonomic nervous system hypothermia in the body temperature range of 60° to 70°F stimulation result from changes in heart rate and from (15.5°–21°C). These effects presumably result from the changes in contractile strength of the heart. fact that heat increases the permeability of the cardiac muscle membrane to ions that control heart rate, result- ing in acceleration of the self-excitation process. EFFECT OF POTASSIUM AND CALCIUM Contractile strength of the heart often is enhanced IONS ON HEART FUNCTION temporarily by a moderate increase in temperature, such In our discussion of membrane potentials in Chapter 5, as that which occurs during body exercise, but prolonged we pointed out that potassium ions have a marked effect temperature elevation exhausts the metabolic systems of on membrane potentials, and in Chapter 6 we noted that the heart and eventually causes weakness. Therefore, opti- calcium ions play an especially important role in activat- mal heart function depends greatly on proper control of ing the muscle contractile process. Therefore, it is not body temperature by the control mechanisms explained surprising that the concentrations of each of these two in Chapter 74. 125 UNIT III The Heart Normal range Dewenter M, von der Lieth A, Katus HA, Backs J: Calcium signal- ing and transcriptional regulation in cardiomyocytes. Circ Res Cardiac output (L/min) 5 121:1000, 2017. Doenst T, Nguyen TD, Abel ED: Cardiac metabolism in heart failure: 4 implications beyond ATP production. Circ Res 113:709, 2013. Eisner DA, Caldwell JL, Kistamás K, Trafford AW: Calcium and 3 excitation-contraction coupling in the heart. Circ Res 121:181, 2 2017. Finkel T, Menazza S, Holmström KM, et al: The ins and outs of mito- 1