SECTION III THE CARDIOVASCULAR SYSTEM Heart Block A 48-year-old man,who engaged in regular physical exercise.went to see his physician because of recurrent headaches.Physical examination revealed that the patient had a mean heart rate of 55 beats/min.His physician noted that the patient's cardiac rhytha varied substantially with the phases of respiration:the heart rate increased during inspiration and decreased during expiration. 1.What changes in cardiac sympathetic and parasympathetic activity take place during the respiratory cyele? 2 Are the respiratory fluctuations in heart rate produced hy the rhythmic changes in sympathetic activity,in parasympathetic activity,or both? The physician diagnosed this patient's headsches as migraine.Be advised the patient to take propranolol,a B-adrenergic receptor antagonist,to relieve the headaches.The physician noted that after the patient had taken the propranolol, the mean heart rate diminished very slightly,and the respiratory fluctuations in heart rate were not appreciably different from those observed before the propranolol was taken. 3.Does the failure of propranolol to induce a substantial change in mean heart rate or in the respiratory fluctuations in heart rate necessarily signify that the patient's cardiac sympathetic neural activity was negligible at the time he was being exanined? Three years later,the patient hegan to experience frequent episodes of chest pain on exertion.The patient's cardiologist recomrended a diagnostic cardiac catheterization.His aortic pressure (Pa)and his electrocardiogram (ECG)were recorded during the procedure:one segment of the record is shoun in Fig.25-1.As the cardiac catheter was heing mnipulated,it initiated several premature ventricular depolarizations,one of which (designated R')is shown in this figure
SECTION III THE CARDIOVASCULAR SYSTEM Heart Block A 48-year-old man, who engaged in regular physical exercise, went to see his physician because of recurrent headaches. Physical examination revealed that the patient had a mean heart rate of 55 beats/min. His physician noted that the patient's cardiac rhythm varied substantially with the phases of respiration; the heart rate increased during inspiration and decreased during expiration. 1. What changes in cardiac sympathetic and parasympathetic activity take place during the respiratory cycle? 2. Are the respiratory fluctuations in heart rate produced by the rhythmic changes in sympathetic activity, in parasympathetic activity, or both? The physician diagnosed this patient's headaches as migraine. He advised the patient to take propranolol, a β-adrenergic receptor antagonist, to relieve the headaches. The physician noted that after the patient had taken the propranolol, the mean heart rate diminished very slightly, and the respiratory fluctuations in heart rate were not appreciably different from those observed before the propranolol was taken. 3. Does the failure of propranolol to induce a substantial change in mean heart rate or in the respiratory fluctuations in heart rate necessarily signify that the patient's cardiac sympathetic neural activity was negligible at the time he was being examined? Three years later, the patient began to experience frequent episodes of chest pain on exertion. The patient's cardiologist recommended a diagnostic cardiac catheterization. His aortic pressure (Pa) and his electrocardiogram (ECG) were recorded during the procedure; one segment of the record is shown in Fig. 25-1. As the cardiac catheter was being manipulated, it initiated several premature ventricular depolarizations, one of which (designated R') is shown in this figure
4.Why did the premsture veatricular depolarization (Fig.25-1)not affect the aortic pressure tracing? 5.Why did the ventricular contraction after the premature heat produce such a large aortic pulse pressure (difference between maximn and ninirun aortic pressures)? About I year later,the patient developed 2:1 atrioventricular (AV)block (i.e.. only alternate cardiac inpulses were propagated fron atria to ventricles).The patient's ECG is shown in Fig.25-2.Note that before the patient was given atropine (top tracing).those P-P intervals that include an R wave are shorter (0.7 s)than those that do not include an R wave (0.8 s). The cardiologist gave the patient test injections of propranolol and of atropine to determine the role of both divisions of the automomic mervous systen in the production of the AY block and of the altermating P-P interval durations.The cardiologist found that propranolol had little effect either on the 2:1 AV block or on the alternation of the P-P intervals.Be also observed that atropine had little effect on the AV block,but it did cause the mean P-P interval to diminish (to 0.6 s),and the alternations of the P-P intervals were no longer evident (bottom tracing). 6.What is the most likely explanation for the alternating durations of the P-P intervals (Fig.25-2)? 7.How do you explain the abolition of the alternations by atropine (Fig.25-2), but the absence of any appreciable effect by propranolol? ASE理 1.Action potentials recorded from efferent nerve fibers to the heart in experimental aninals indicate that sympathetic activity increases and vagal activity decreases during inspiration.The opposite changes take place during expiration
4. Why did the premature ventricular depolarization (Fig. 25-1) not affect the aortic pressure tracing? 5. Why did the ventricular contraction after the premature beat produce such a large aortic pulse pressure (difference between maximum and minimum aortic pressures)? About 1 year later, the patient developed 2:1 atrioventricular (AV) block (i.e., only alternate cardiac impulses were propagated from atria to ventricles). The patient's ECG is shown in Fig. 25-2. Note that before the patient was given atropine (top tracing), those P-P intervals that include an R wave are shorter (0.7 s) than those that do not include an R wave (0.8 s). The cardiologist gave the patient test injections of propranolol and of atropine to determine the role of both divisions of the autonomic nervous system in the production of the AV block and of the alternating P-P interval durations. The cardiologist found that propranolol had little effect either on the 2:1 AV block or on the alternation of the P-P intervals. He also observed that atropine had little effect on the AV block, but it did cause the mean P-P interval to diminish (to 0.6 s), and the alternations of the P-P intervals were no longer evident (bottom tracing). 6. What is the most likely explanation for the alternating durations of the P-P intervals (Fig.25-2)? 7. How do you explain the abolition of the alternations by atropine (Fig. 25-2), but the absence of any appreciable effect by propranolol? ANSWER 1. Action potentials recorded from efferent nerve fibers to the heart in experimental animals indicate that sympathetic activity increases and vagal activity decreases during inspiration. The opposite changes take place during expiration
2.The changes in activity in both divisions of the autononic nervous system would tend to contribute to the respiratory sinus arrhythmia (i.e..to the observed alterations in heart rate throughout the respiratory cyele).However,when atropine (which blocks the cardiac effects of the vagal activity)is given,the respiratory sinus arrhythmia usually disappears entirely.However,when propranolol (which blocks the cardiac effeets of the sympathetic activity)is given,the respiratory sinus arrhythia is scarcely affected. The vagal influence usually predoainates over the sympathetic influence as a mediator of respiratory simus arrhythaia for several reasons.First:in normal resting individuals.vagal activity is usually substantial.whereas sympathetic activity is usually minimal.Second,this disparity in activity is usually exaggerated in people who exercise regularly.Third,and probably most important, the time courses of the vagal and sympathetic effects on the heart are entirely different.The vagal effects produce their responses very quickly (relative to the duration of a respiratory eyele).and the vazal responses also decay very quickly after vagal activity ceases.Conversely.the onset and decay of the cardiac respomses to sympathetic activity are much more sluggish.Periodie changes in sympathetic activity associated with the respiratory cycle camnot produce appreciable changes in cardiac function within the usual tine course of a respiratory cycle,because the cardiac changes develop so slowly at the beginning of any brief period of sympathetic activity and the cardiac changes also decay very slowly after the sympathetic activity ceases. 3.The failure of propranolol to induce any substantial change in mean heart rate or in the respiratory fluctuations in heart rate does not necessarily signify that the activity in the cardiac sympathetic nerves was negligible.The slow heart rate (55 beats/min)and the prominemt respiratory sinus arrbythmia suggest that the vagal tone in this patient was considerable.Under such conditions,the vagal influence on heart rate would predominate,even if sympathetic activity also was substantial.The summation of sympathetic and vagal effects on heart rate is highly nonlinear.One of the principal mechanisns responsible for the vagal predominance
2. The changes in activity in both divisions of the autonomic nervous system would tend to contribute to the respiratory sinus arrhythmia (i.e., to the observed alterations in heart rate throughout the respiratory cycle). However, when atropine (which blocks the cardiac effects of the vagal activity) is given, the respiratory sinus arrhythmia usually disappears entirely. However, when propranolol (which blocks the cardiac effects of the sympathetic activity) is given, the respiratory sinus arrhythmia is scarcely affected. The vagal influence usually predominates over the sympathetic influence as a mediator of respiratory sinus arrhythmia for several reasons. First: in normal resting individuals, vagal activity is usually substantial, whereas sympathetic activity is usually minimal. Second, this disparity in activity is usually exaggerated in people who exercise regularly. Third, and probably most important, the time courses of the vagal and sympathetic effects on the heart are entirely different. The vagal effects produce their responses very quickly (relative to the duration of a respiratory cycle), and the vagal responses also decay very quickly after vagal activity ceases. Conversely, the onset and decay of the cardiac responses to sympathetic activity are much more sluggish. Periodic changes in sympathetic activity associated with the respiratory cycle cannot produce appreciable changes in cardiac function within the usual time course of a respiratory cycle, because the cardiac changes develop so slowly at the beginning of any brief period of sympathetic activity and the cardiac changes also decay very slowly after the sympathetic activity ceases. 3. The failure of propranolol to induce any substantial change in mean heart rate or in the respiratory fluctuations in heart rate does not necessarily signify that the activity in the cardiac sympathetic nerves was negligible. The slow heart rate (55 beats/min) and the prominent respiratory sinus arrhythmia suggest that the vagal tone in this patient was considerable. Under such conditions, the vagal influence on heart rate would predominate, even if sympathetic activity also was substantial. The summation of sympathetic and vagal effects on heart rate is highly nonlinear. One of the principal mechanisms responsible for the vagal predominance
is that the acetylcholine released from vagal nerve endings acts to inhibit the release of porepinephrine fron neighboring sympathetic nerve endings.Thus even if sympathetic neural activity were substantial.the sympathetic nerve endings might not release much norepinephrine if the tissue concentration of acetylcholine were appreciable in the region of the sympathetie nerve terminals.Under such conditions,propranolol would probably have little infloence on heart rate. 4.When a ventricular depolarization is very prenature (as in R'in Fig.25-1). the time for ventricular filling is severely limited,the sarcomeres will not be stretched optimally,and therefore the contractions will be weak (Frank-Starling mechanisn).Furtherpore,prerature depolarization affects the intracellular Catt distribution and hence the strength of contraction.During each heartbeat.the Ca++ that dissociates froa the coatractile proteins is rapidly taken up by the sarcoplasnic reticulu (SR)during relaxation.However,several hundred milliseconds must elapse before that Cat+is fully available to be released again by the Sk.Hence,very premature comtractions are associated with a meager release of Ca++from the SR,and therefore the premature contraction is feeble.In the patient whose tracings are shown in Fig.25-1,the premature contraction evidently did not generate a sufficfently high intraventricular pressure to force open the aortic valves and to eject blood into the aorta.Therefore the premature contraction had no evident effect on the aortic pressure tracing. 5.The sane factors operate,but in the opposite direction.to explain the large pulse pressure for the contraction after the premature beat (Fig.25-1).The long pause (compensatory pause)after the premature beat allowed a prolonged filling time for the ventricles.and therefore the increased sarcomere stretch augnented the cardiac comtraction (Frank-Starling nechanisa).Furthermore,the compensatory pause also allowed more than sufficient time for the sarcoplasmie reticulun to release the Ca++that had been taken up during both the premature beat and the beat that preceded it.Therefore the contraction that followed the premature beat could
is that the acetylcholine released from vagal nerve endings acts to inhibit the release of norepinephrine from neighboring sympathetic nerve endings. Thus even if sympathetic neural activity were substantial, the sympathetic nerve endings might not release much norepinephrine if the tissue concentration of acetylcholine were appreciable in the region of the sympathetic nerve terminals. Under such conditions, propranolol would probably have little influence on heart rate. 4. When a ventricular depolarization is very premature (as in R' in Fig. 25-1), the time for ventricular filling is severely limited, the sarcomeres will not be stretched optimally, and therefore the contractions will be weak (Frank-Starling mechanism). Furthermore, premature depolarization affects the intracellular Ca++ distribution and hence the strength of contraction. During each heartbeat, the Ca++ that dissociates from the contractile proteins is rapidly taken up by the sarcoplasmic reticulum (SR) during relaxation. However, several hundred milliseconds must elapse before that Ca++ is fully available to be released again by the SR. Hence, very premature contractions are associated with a meager release of Ca++ from the SR, and therefore the premature contraction is feeble. In the patient whose tracings are shown in Fig. 25-1, the premature contraction evidently did not generate a sufficiently high intraventricular pressure to force open the aortic valves and to eject blood into the aorta. Therefore the premature contraction had no evident effect on the aortic pressure tracing. 5. The same factors operate, but in the opposite direction, to explain the large pulse pressure for the contraction after the premature beat (Fig. 25-1). The long pause (compensatory pause) after the premature beat allowed a prolonged filling time for the ventricles, and therefore the increased sarcomere stretch augmented the cardiac contraction (Frank-Starling mechanism). Furthermore, the compensatory pause also allowed more than sufficient time for the sarcoplasmic reticulum to release the Ca++ that had been taken up during both the premature beat and the beat that preceded it. Therefore the contraction that followed the premature beat could
eject a supernornal stroke volune and thereby produce the large arterial pulse pressure. 6.The baroreceptor reflex is probahly the principal nechanisn responsible for the alternating P-P intervals (Fig.25-2)that are often observed in patients with 2:1 AV block.This distinctive rhythm,which is referred to as ventriculophasic sinus arrhythmia.is characterized hy cyclic fluctuations in arterial blood pressure (Pa) associated with the alternating presence and absence of a ventricular contraction during consecutive P-P intervals.During the cardiac cycles in which the ventricles contract and eject blood,Pa rises from its diastolic value to its systolic value. and then begins to fall again.During such a cycle.the arterial baroreceptors are stimulated by the rise in Pa.and after a brief delay.they increase cardiac vagal activity and decrease cardiac sympathetic activity.During the altermate cycles. the ventricles fail to contract,and therefore Pa falls below the level attained at the end of the preceding cardiac cycle.Bence,vagal activity progressively diminishes and sympathetic activity rises. Usually the reflex delay initiated by the systolic rise in Pa is sufficiently long that it does not prolong the concurrent cardiac cycle.Instead,the ventricular contraction usually causes the subsequent P-P interval (ome that does not include an R wave)to be prolonged.Occasionally.however.the temporal relation between the reflex delay and the cardiac cycle length is such that those P-P intervals that do contain the R waves are the intervals that are proloeged,and the P-P intervals that do not include an R wave are abridged. 7.Although the cyclic alternation in Pa does alter both vagal and sympathetic neural activity in each cardiac eyele,the alternating changes in P-P interval can usually be abolished completely by atropine,but propranolol will have little influence.The main reason for this is that vagally nediated cardiac responses cam be initiated and terminated rapidly,within the time constraints of an ordinary cardiac cyele,whereas sympathetically nediated responses are much more sluagish and cannot induce appreciable changes beat by beat
eject a supernormal stroke volume and thereby produce the large arterial pulse pressure. 6. The baroreceptor reflex is probably the principal mechanism responsible for the alternating P-P intervals (Fig. 25-2) that are often observed in patients with 2:1 AV block. This distinctive rhythm, which is referred to as ventriculophasic sinus arrhythmia, is characterized by cyclic fluctuations in arterial blood pressure (Pa) associated with the alternating presence and absence of a ventricular contraction during consecutive P-P intervals. During the cardiac cycles in which the ventricles contract and eject blood, Pa rises from its diastolic value to its systolic value, and then begins to fall again. During such a cycle, the arterial baroreceptors are stimulated by the rise in Pa, and after a brief delay, they increase cardiac vagal activity and decrease cardiac sympathetic activity. During the alternate cycles, the ventricles fail to contract, and therefore Pa falls below the level attained at the end of the preceding cardiac cycle. Hence, vagal activity progressively diminishes and sympathetic activity rises. Usually the reflex delay initiated by the systolic rise in Pa is sufficiently long that it does not prolong the concurrent cardiac cycle. Instead, the ventricular contraction usually causes the subsequent P-P interval (one that does not include an R wave) to be prolonged. Occasionally, however, the temporal relation between the reflex delay and the cardiac cycle length is such that those P-P intervals that do contain the R waves are the intervals that are prolonged, and the P-P intervals that do not include an R wave are abridged. 7. Although the cyclic alternation in Pa does alter both vagal and sympathetic neural activity in each cardiac cycle, the alternating changes in P-P interval can usually be abolished completely by atropine, but propranolol will have little influence. The main reason for this is that vagally mediated cardiac responses can be initiated and terminated rapidly, within the time constraints of an ordinary cardiac cycle, whereas sympathetically mediated responses are much more sluggish and cannot induce appreciable changes beat by beat
