20-3 The eanteot [70ST ‘The Action Potential in Skeletal and Cardiac Muscle. The Navigator icon in the shadow box highlights the topic we will consider inthis section. (a) ‘An action potential in a ventricular muscle cel. (b) The relationship between an action potential and a twitch contraction in skeletal muscle and cardiac muscle The shaded areas indicate the duration of the absolute (green) and relative (beige) refractory periods. FIGURE 20-15, id sxetetay use i sal stot tert es 7 |\ = os ats 5 Wire ome STEPS Rapid] [ STEPa Tho Plateau | [ STEPS: Foporcaton] ie paterson | | se: Cat Cane: Cause: Nat entry oration: -178mbec | | Duron 7S msec zt) Epos ‘Duration: 3-5 msec Ends with: Closure of | Ends with: Closure of MUSCLE | Raed ea [slow calcium channels| | slow potassium channels | [sodium channels mv] Action potentics Ql sie ela | Absolute refractory Period 700 Time (msec) (@) Cardiac muscle -20) 200 [OTHE CARDIAC CYCLE Each heartbeat is followed by a brief resting phase, allowing time for the chambers to relax and prepare for the next heart beat. The period between the start of one heartbeat and the be- ginning of the next is a single eardiac cycle. The cardiac cycle, therefore, includes alternating periods of contraction and te- laxation. For any one chamber in the heart, the cardiac cycle can be divided into two phases: (I) systole and (2) diastole. During systole (SIS-t6-I8), or contraction, the chamber con- tracts and pushes blood into an adjacent chamber or into an arterial trunk, Systole is followed by diastole (4i-AS-t-Ié), or relaxation. During diastole, the chamber fills with blood and prepares for the next cardiac cycle. Fluids move from an area of high pressure to one of lower pressure. In the course of the cardiac cycle, the pressure within each chamber rises during systole and falls during diastole. Valves between adjacent chambers help ensure that blood flows in the Time (msec) ———> CO) desired direction, but blood will flow from one chamber to an- ‘other only ifthe pressure in the first chamber exceeds that in the second. This basic principle governs the movement of blood be- ‘ween atria and ventricles, between ventricles and arterial trunks, and between major veins and atria ‘The correct pressure relationships are dependent on the care- ful timing of contractions. For example, blood could not move in the desired direction if an atrium and its attached ventricle con- twacted at precisely the same moment. The elaborate pacemaking and conducting systems normally provide the required spacing between atrial and ventricular systoles. At a representative heart rate of 75 bpm, a sequence of systole and diastole in either the atria or the ventricles lasts 800 msec. For convenience, we shall assume that the cardiac cycle is determined by the atria and that i includes one cycle of atrial systole and atrial diastole. This con- vention follows our description of the conducting system and the propagation of the stimulus for contraction.J 704) charter 20. THE HEART Heart Attacks Tn a myocardial (mi-8-KAR-d2-al)infaretion (MI), or AW eartreack, part f the coronary craton becomes blocked and cardiac muscle cells die from lack of oxygen. The affected tissue then degenerates, creating a nonfunctional area known as an infarct. Heart attacks most commonly result from severe coronary artery disease (CAD, p. 695). The con sequences depend on the site and nature of the circulatory blockage. If it occurs neat the start of one of the coronary ar- series, the damage will be widespread and the heart may stop ‘beating. I the blockage involves one of the smaller arterial branches, the individual may survive the immediate criss but may have many complications all unpleasant. As scar tissue forms in the damaged area, the heartbeat may become irregu- lar and other vessels can become constricted, creating addi- tional circulatory problems. Myocardial infarctions are generally associated with fixed blockages, such as those seen in CAD. When the crisis devel- ‘pss a result of thrombus (clot) formation ata plaque, the condition is called coronary thrombosis. A vessel already narrowed by plague formation may also become blocked by a sudden spasm in the smooth muscles of the vascular wal The individual then may experience intense pain, similar to that felt in an angina attack, but persisting even at res. However, pain does not always accompany a heart attack, and silent heart attacks may be even more dangerous than more apparent, because the condition may go undiagnosed and may not be treated before a fatal MI occurs. Roughly 25 percent of heart attacks are not recognized when they occur. The eytoplasm of a damaged cardiac muscle cel differs from that of normal muscle cell As the supply of oxygen decreases, the cells become more dependent on anaerobic metabolism to meet their energy needs. > ». 17 Over time, the cytoplasm accumulates large numbers of enzymes involved with anaerobic energy production. As the mem- branes of the cardiac muscle cells deteriorate, these enzymes enter the surrounding intercellular fluids. The appearance of such enzymes in the circulation thus indicates that an infarct has occurred, The enzymes that are tested for in a diagnostic blood test include lactate dehydrogenase (LDH), serum glu- tamic oxaloacetic transaminase (SGOT, also called aspartate mninotransferase), creatine phosphokinase (CPK or CK), and a special form of creatine phosphokinase that occurs only in cardiac muscle (CK-MB). (These enzyme described, and normal and abnormal results are considered, in the cardiovascular section of the Applications Manual.) About 25 percent of ML patients die before obtaining ‘medical assistance, and 6 percent of MI deaths among those under age 50 occur within an hour after the initial infarc. ‘The goals of treatment are to limit the size ofthe infarct and to avoid additional complications by preventing irregular contractions, improving circulation with vasodilators, pro- viding additional oxygen, reducing the cardiac workload, and, if possible, eliminating the cause of the circulatory blockage. Anticoagulants (even aspirin chewed and swal- lowed at the start ofan MI) may help prevent the formation of additional thrombi, and clot-dissolving enzymes may re- duce the extent of the damage if they are administered with six hours after the MI occurred. Current evidence suggests that tissue plasminogen activator (t-PA). which is relatively expensive, is more beneficial than other fibrinolytic agents, such as urokinase or streptokinase. = p. 076 Follow-up treatment with heparin, aspirin, or both is recommended; without further treatment, the circulatory blockages will reappear in about 20 percent of patients. Roughly 1.3 million MIs occur in the United States each year, and half the victims die within a year of the incident. ‘The following factors appear to increase the risk of a heart at tack: (1) smoking, (2) high blood pressure, (3) high blood cholesterol levels, (4) high circulating levels of low-density lipoproteins (LDLs), (5) diabetes, (6) male gender (below age 70), (7) severe emotional stress (8) obesity, (9) genetic pre- disposition, and (10) a sedentary lifestyle. We shall consider the role of lipoproteins and cholesterol in plaque formation and heart disease in Chapter 21. Although the heart attack rate of women under age 70 is lower than that of men, the mortality rate for women is higher—perhaps because heart disease in women is neither diagnosed as early nor treated as aggressively as that in men. TThe presence of two risk factors more than doubles the risk of heart attack, so eliminating as many risk factors as possible will improve the chances of preventing or surviving a heart attack. Changing the diet to limit cholesterol, exercis- ing to lower weight, and seeking treatment for high blood pressure are steps inthe right direction. It has been estimated that a reduction in coronary risk factors could prevent 150,000 deaths each year in the United States alone.Phases of the Cardiac Cycle ‘The phases of atrial systole, atrial diastole, ventricular systole, and ventricular diastole are diagrammed in Figure 20-16e for a heart rate of 75 bpm. As this cardiac cycle begins, all four chambers are relaxed and the ventricles are partially filled with blood. During atrial systole, the atria contract, filling the ventricles completely (f Ventricular diastole—tate: All chambees are relaxed Ventricls fil passively sro mses (6) Ventricular diastole— carly: As ventcls relax, pressure in ventricles drops Blood flows back against cusps of somiunar valves and forces, ‘them closed. Blood flows into the relaxed ata, 20-3 Te Heantest (TOE with blood (Figure 20-16a,be). Atrial systole lasts 100 msec, Over this period, blood cannot flow into the atria because atrial pressure exceeds venous pressure. Yet there is very litle backflow into the veins, even though the connections with the venous system lack valves, because blood takes the path of least resistance. Resistance to blood flow through the broad AV connections and into the ven- trices is less than that through the smaller, angled openings of the large veins, which are connected to miles of smaller vessels—many of which do have valves. The atria next enter atrial diastole, which continues until the start of the next cardiac cycle. Atrial diastole and ventricular sys- tole begin at the same time. Ventricular systole lasts 270 msec. During this period, blood is pushed through the systemic and pulmonary circuits and toward the aria (Figure 20-16c,de). The heart then enters ventricular diastole (Figure 20-16e,fe), which lasts 530 msec (the 430 msec remaining in this cardiac cycle, plus FIGURE 20-16 Phases of the Cardiac Cycle. Thin black arrows indicate blood flow, and green arrows indicate contractions, (a) Atrial systole begins: ‘Atal contraction forces ‘2 small amount of aditional ‘blood into relaxed ventricles. (0) Atrial systole ends atrial diastole begins valves closed but doos ot erate enough pressure to open semiunar valves. ¢ / (6) Ventricular systole— first phase: Ventricular contraction pushes AV (8 Votre systole ‘cond phan: ke ventfcar Frooiefoe andere caus fe wien he er vvs oper ans ? Boos octeE16 CHAPTER 20 THE HEART the first 100 msec ofthe next). For the rest of this eycle, filling oc- curs passively and both the atria and the ventricles are relaxed ‘The next cardiac cycle begins with atrial systole and the comple tion of ventricular filling. When the heart rate increases, all the phases of the cardiac cydle are shortened. The greatest reduction occurs inthe length of time spent in diastole. When the heart rate climbs from 75 bpm to 200 bpm, the time spent in systole drops by less than 40 percent, but the duration of diastole is reduced by almost 75 percent. Pressure and Volume Changes in the Cardiac Cycle In considering the pressure and volume changes that occur dur- ing the cardiac cycle, we shall use reference numbers that match those in Figure 20-17e, which follow pressures and volumes within the left atrium and left ventricle. The discussion applies to both sides of the heart. Although pressures are lower in the right atrium and right ventricle, both sides of the heart contract at the same time, and they eject equal volumes of blood Tine ese) a ee EAE AT EOE ONC OO Es! ee complex conta — cxrogran ‘eca) P iz P aaa AC ARAL piasTOLe | SYSTOLE ATRIAL DUSTOLE ‘SYSTOLE VENTRICULAR TERTRISOTAR ene ee VENTRICULAR DASTOLE ; ae ‘ore valve | oo ee can wh tn Pressure (mm Hg) Left lo 30- atrium Lott AV un ° lee |End-diastolic| aa Lett | a me i » ‘FIGURE 20-17 Pressure and Volume Relationships in the Cardiac Cycle. Major features of the cardiac cycle are shown for a heart rate of 75 bpm. The circled numbers correspond to the associated numbered list in the text.ATRIAL SYSTOLE The cardiac cycle begins with atrial systole, which lasts about 100 msec in a resting adult: 1, As the atria contract, rising atrial pressures push blood into the ventricles through the open right and left AV valves. 2. At the start of atrial systole, the ventricles are already filled to about 70 percent of their nérmal capacity, due to passive blood flow toward the end of the previous cardiac cycle. As the atria contract, rising atrial pressures provide the missing 30 percent by pushing blood through the open AV valves. Atrial systle es sentially “tops off” the ventricles. 3. At the end of atrial systole, each ventricle contains the maximum amount of blood that it will holdin this cardiac eyele. That quanti- ty is called the end-diastolic volume (EDV). In an adult who is standing at rest, the end-diastolic volume is typically about 130 ml, VENTRICULAR SYSTOLE As atrial systole ends, ventricular systole begins. This period lasts approximately 270 msec in a resting adult. As the pressures in the ventricles rise above those in the atria, the AV valves swing shut. 4. During this stage of ventricular systole, the ventricles are contract ing, Blood flow has yet to occur, however, because ventricular pressures are not high enough to force open the semilunar valves and push blood into the pulmonary or aortic teunk. Over this pe- riod, the ventricles contract isometrically: They generat tension and ventricular pressure rise, but blood flow does not occur. The ‘ventricles are now in the period of isovolumetric contraction: ll the heart vahes are closed, the volumes of the ventricles remain constant, and ventricular pressures rise. 5. Once pressure in the ventricles exceeds that in the arterial trunks, the semilunar valves open and blood flows into the pul- monary and aortic trunks. This point marks the beginning of the period of ventricular ejection. The ventricles now contract isotonically: The muscle cells shorten, and tension production remains relatively constant. (To review isotonic versus isomet- ric contractions, see Figure 10-186, p. 314) After reaching a peak, ventricular pressures gradually decline near the end of ventricular systole. Figure 20-17 shows values for the left ventricle and aorta. Although pressures in the right ventricle and pulmonary trunk are much lower, the right ventri- cle also goes through periods of isovolumetric contraction and ventricular ejection. During ventricular ejection, each ventricle will eject 70-80 ml of blood, the stroke volume (SV) of the heart. The stroke volume at res is soughly 60 percent of the end- diastolic volume. This percentage, known as the ejection faction, can vary in response to changing demands on the heart. (We shall discuss the regulatory mechanisms in the next section.) 6. As the end of ventricular systole approaches, ventricular pres- sures fall rapidly Blood in the aorta and pulmonary trunk now starts to flow back toward the ventricles, and this movement clos- «the semilunar valves. As the backflow begins, pressure decreas- «sin the aorta. When the semilunar valves close, pressure rises again as the elastic arterial walls recoil. Ths small, temporary rise produces a valley in the pressure tracing that is called a dicrotic (di-KRO-tik) notch (dikrotos, double beating). The amount of 20-5 The Heartbeat blood remaining in the ventricle when the semilunar valve closes is the end-systolic volume (ESV). At rest, the end-systolic vol- ‘ume is 50 ml, about 40 percent of the end-diastolic volume, VENTRICULAR DIASTOLE The period of ventricular diastole lasts for the 430 msec remaining in the current cardiac cycle and con- tinues through atrial systole in the next cycle. 7. All the heart valves are now closed, and the ventricular my- ‘ocardium is relaxing. Because ventricular pressures are still higher than atrial pressures, blood cannot flow into the ventri- les. This i the period of isovolumetric relaxation. Ventricular pressures drop rapidly over this period, because the elasticity of the connective tissues of the heart and fibrous skeleton helps re- ‘expand the ventricles toward their resting dimensions. 8, When ventricular pressures fall below those ofthe atria, the atr- al pressures force the AV valves open. Blood now flows from the atria into the ventricles. Both the atria and the ventricles are in diastole, but the ventricular pressures continue to fall as the ven- tricular chambers expand. Throughout this period, pressures in the ventricles are so far below those in the major veins, that blood pours through the relaxed atria and on through the open AY valves into the ventricles. This passive mechanism is the pri- mary method of ventricular filling, The ventricles will be nearly three-quarters full before the cardiac cycle ends. ‘The relatively minor contribution that atrial systole makes to ventricular volume explains why individuals can survive quite normally when their atria have been so severely damaged that they can no longer function. In contrast, damage to one or both ventricles can leave the heart unable to maintain adequate blood flow through peripheral tissues and organs. A condition of heart failure then exists, ET veo faire Heart Sounds Listening to the heart, a technique called auscultation, isa simple and effective method of cardiac diagnosis. Physicians use an in- strument called a stethoscope to listen to normal and abnormal heart sounds. Where to place the stethoscope depends on which valve is under examination (Figure 20-18ae). Valve sounds must pass through the pericardium, surrouneling tissues, and the chest wall, and some tissues muffle sounds more than others. As a re- sult, the placement of the stethoscope does not always corre- spond to the position of the valve under review. ‘There are four heart sounds, designated as S, through S, (Figure 20-18be). When you listen to your own heart, you usual- ly hear the first and second heart sounds. These sounds accompa ny the closing of your heart valves. The first heart sound, known as“lubb” (S,), lasts atte longer than the second, called “dup” (S,).Sip which marks the start of ventricular contraction, is pro- duced as the AV valves close; $2 occurs at the beginning of ven- tricular filing, when the semilanar valves close. Third and fourth heart sounds may be audible, but they are usu- ally very faint and seldom are detectable in healthy adults. These sounds are associated with blood flowing into the ventricles (S,) and atrial contraction (S,), rather than with valve action,Gy 708 | cHaPTER 20 THEHEART Sounds heard] Aortic Valve location valve ‘Sounds heard] Lett Valve location AV Valve location] Right 5, ‘Sounds neard} AV Heart sounds |__ FIGURE 20-18 Heart Sounds. (a) Placements ofa stethoscope for listening to the diferent sounds produced by individual valves. {(b) The timing of heart sounds in relation to key events in the cardiac cycle. Minor valve abnormalities are relatively common, For ex- ample, to 10 percent of healthy individuals have some de- sree of mitral valve prolapse, a condition in which the mitral valve cusps do not close properly. The problem may involve ab- normally long (or short) chordze tendineae or malfunctioning papillary muscles, Because the valve doesnot work perfectly, some regurgitation may occur during left ventricular systole. The surges, swirls, and eddies that accompany regurgitation create a rushing, gurgling sound known asa heart murmur. ‘Minor heart murmurs are very common. Most individuals with this condition are completely asymptomatic and live normal lives, unaware of any circulatory malfunction. E treme prolapse and valve failure, which may be caused by breakage of the chordae tendineae, can be life threatening ‘This condition is known asa mitral valve flail The Energy for Cardiac Contractions When a normal hearts beating, the energy required is obtained by the mitochondrial breakdown of fatty acids (stored as lipid droplets) and glucose (stored as glycogen). These aerobic reactions can occur only when oxygen is readily available, = p.316 In addition to obtaining oxygen from the coronary circula- tion, cardiac muscle cells maintain their own sizable reserves of oxygen. In these cells, oxygen molecules are bound to the heme units of myoglobin molecules. (We discussed this globular protein, which reversibly binds oxygen molecules, and its func tion in muscle fibers in Chapter 10.) == p. 320 Normally, the combination of circulatory supplies plus myoglobin reserves is enough to meet the oxygen demands of your heart, even when itis working at maximum capacity. Isthe heart always pumping blood when pressure inthe lft ventricle is rising? Explain 7 What factor oF factors could cause an increase in the size of the QRS complex ofan electrocardiogram recording? ‘Aner arom pge 1 Review the entire cardiac eycle on the IP CD-ROM: Cardiovascular System/Cardiac Cycle. 20-4 CARDIODYNAMICS Objectives ® Define cardiac output, and describe the factors that influence this variable. ® Describe the variables that influence heart rate. ® Describe the variables that influence stroke volume. ® Explain how adjustments in stroke volume and cardiac output are coordinated at different levels of activity. ‘The term cardiodynamics refers to the movements and forces generated during cardiac contractions. Each time the heart beats, the two ventricles eject equal amounts of blood. Earlier wwe introduced these terms: