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Effects of atrial and ventricular tachycardia on the cardiovascular dynamics in reserpinized dogs
Effects of Atria1 and Ventricular on the Cardiovascular Reserpinized
Tachycardia
Dynamics in Dogs*
JIRO NAKANO, M.D. Oklahoma
City, Oklahoma
GENTLY it was observed that atria1 and ventricular tachycardia resulted in increased sympathoadrenal activity by decreasing mean arterial and pulse pressures.1-3 It has been known that reserpine depletes catecholamine contents of various tissues495 and decreases myocardial contractile force.5,s The present study was undertaken to compare the effect of tachycardia on the cardiovascular dynamics in control animals with that in reserpinized animals.
recorded continuously with an Electronics for Medicine recorder (Model DR8). Atria1 or ventricular tachycardia with rates ranging from 200 to 240 beats/min. was induced with a Crass stimulator (Model S4). D.C. stimuli of about 5 msec. in duration and of liminal intensity were applied to the left atria1 appendage or to the apical region of the left ventricle through two fish-hook electrodes.
RESULTS Control Dogs: The results observed were consistent in all experiments. Tracings of representative experiments in control and reserpinized dogs are illustrated in Figures 1 and 2. The results of the hemodynamic effects of ventricular tachycardia with equivalent rates in two groups of dogs are summarized in Figure 3. In control dogs, as shown in Figure l,A and B, the induction of tachycardia resulted in sudden reductions in mean arterial pressure, cardiac output and myocardial contractile force, while left and right atria1 pressures increased significantly. Within one to two minutes. after the onset, mean arterial pressure and cardiac output returned toward control values (Fig. 1). Left and right atria1 pressures remained elevated. Usually mean arterial pressure and cardiac output stabilized at levels significantly below controls, while myocardial contractile force increased considerably above control value and stabilized at that level. On termination of tachycardia, both mean arterial pressure and cardiac output increased markedly above control levels, whereas myocardial contractile force, left atria1 pressure and right atria1 pressure returned to controls rather abruptly. Within two to three minutes after the end of
METHODS Thirty dogs weighing between 20.5 and 25.0 kg. were anesthetized with intravenous administration of sodium pentobarbital (20 to 30 mg./kg.). In 15 dogs, a single dose (0.5 to 1 mg./kg.) of reserpine was given intravenously about 24 hours prior to the experiment. The left hemithorax was opened under artificial respiration. The pericardium was incised and the heart suspended in a pericardial cradle. The method used to measure continuously cardiac output (minus coronary blood flow) with a ShipleyWilson rotamete? was a procedure previously described.l12 In all experiments, 5 mg./kg. of sodium heparin was administered intravenously before cannulation of the vessels and 2.5 mg./kg. was repeated every half hour. Mean arterial pressure and left and right atria1 pressures were measured continuously with Statham pressure transducers (P23AA) connected to catheters placed, respectively, in the root of aorta, in the left atrium through a pulmonary vein and in the right atrium through a branch of the right external jugular vein. Continuous measurement of heart rate and myocardial contractile force were made with an Electronics for Medicine tachometer and by a Walton-Brodie strain gauge arch,8 which was sutured directly to the left ventricular muscle. All the hemodynamic parameters, except heart rate, were
* From the Department of Pharmacology, University of Oklahoma School of Medicine, Oklahoma City, Okla. This work was supported in part by research grants (HE-07334, HE-08057 and H-31 11) from the U. S. Public Health Service. JULY
1964
89
‘EWWX,.,AR
133
‘ACHYCARDIC
FIG. 1. X, effects of \wtricular tachycardia OII mywardial contractllc iorcc (MCF 1, lcfr atria1 pressure (LAP), and mean arterial blood pressure (MABP) in a control dog. B. effects of ventricular tachycardia on left atria1 pressure (LAP), right atria1 pressure (RAP), cardiac output (CO) and mean arterial blood pressure (MABP) in a control dog. C, effects of ventricular tachycardia on left atria1 pressurr (LAP), mean arterial blood pressure (MABP). cardiac output (CO) and myocardial contractile force (MCF) in a reswpinizc-d dog.
tachycardia, all hemodynamic parameters returned to control values. Reser@inized Dogs: On the other hand, upon the onset of tachycardia in reserpinized dogs, mean arterial pressure, cardiac output and myocardial contractile force decreased suddenly, and then decreased further very slowly before stabilizing at levels considerably below controls (Fig. IC and 2). Left atria1 pressure increased rather suddenly at the onset and remained at that level. During tachycardia, contractile force was always alternated in its amplitude one beat from another, synchronizing with alternations of arterial pressure pulse; i.e., pulsus alternans. At cessation of tachycardia, cardiac output, myocardial contractile force and mean arterial pressure increased
gradually toward control values. Myocardial contractile force usually decreased further before complete recovery, although pulsus alternans as well as alternations of amplitude of contractile force disappeared at the end of tachycardia. Occasionally, mean arterial pressure increased over control level three to eight minutes after the end of tachycardia. As shown in Figure 2, when a single dose (1 pg./kg.) of isoproterenol or epinephrine was given intravenously about three minutes after the induction of tachycardia in reserpinized dogs, pulsus alternans and coinciding alternations of myocardial contractile force disappeared for approximately four minutes. In addition, during this period, the drugs also increased mean arterial pressure and myocardial contractile force and decreased left THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Tachycardia,
Reserpine
and
Cardiovascular
Dynamics
71
FIG. 2.
Effects of atria1 tachycardia on electrocardiogram (EGG), left atria1 pressure (LAP), aortic blood pressure contractile force (MCF) in a reserpinized dog. Atria1 tachycardia was induced between the first and third vertical arrows. At the second arrow, isoproterenol (1 pg. /kg.) was given intravenously. ( ABP), and myocardial
atria1 pressure, whereas the electrocardiogram revealed a significant elevation of S-T segment and reversal of T wave. DISCUSSION
From the present study it is clear that the evolutional changes following the beginning and the end of atria1 or ventricular tachycardia in control dogs are considerably different from those in reserpinized dogs (Fig. 3). In control dogs, following a short phase of sudden decreases on the onset of tachycardia, mean arterial pressure, cardiac output and myocardial contractile force improve gradually toward control values with myocardial contractile force actually increasing above control. On the other hand, in reserpinized dogs, the compensatory hemodynamic adjustments subsequent to the onset of tachycardia are not observed. Initial, abrupt decreases in mean arterial pressure, cardiac output and myocardial contractile force are followed by further gradual decreases in these parameters before stabilizing at lower levels than those observed in control dogs. In addiJULY
1964
tion, in reserpinized dogs, tachycardia always results in pulsus alternans synchronous with the alternation of the amplitude of myocardial contractile force (Fig. 2). The absence of the hemodynamic improvements in the earlier period of tachycardia already mentioned may be most likely due to the lack of or to insufficient participation of sympathoadrenal activity, since reserpine is known to deplete catecholamine contents of various tissues4 The causative mechanism of pulsus alternans has not been adequately elucidated as yet, although it has been known to occur under various pathophysiologic conditions which may interfere with ventricular function directly or indirectly.+” Lee and Shidemanb and Nayler6 showed that reserpine markedly decreases myocardial contractile force in the cat papillary muscles and toad ventricle, as the catecholamine contents of the myocardium decreased or were depleted markedly.6 Recently, %amiP observed that large doses of reserpine caused irreversible extensive myocardial damage through some unknown mechanism. It is rather diffi-
CONTROL DOGS
(n=lO)
HEART RATE beatVmin
~WI-
MEAN ARTERIAL PRESSURE
2ce
m-
r-s-x-
RESERFlNlZED
DOGS(n=lO) -
+
+
C TI RRI
Ra
0
mm4 0
CARDIAC OUTPUT a%
l@xlOL
l-7-WI
+
C TI RRI
-&-x4+ *
Rz
C TI T2 RI Q
FIG. 3. Effects of ventricular tachycardia on mean arterial pressure, cardiac output and myocardial contractile force in control dogs and reserpinized dogs. The bars represent the average values. C = control value. T1 and RI = values obtained immediately after the onset and end of ventricular tachycardia, respectively. Tt and RS = values obtained 3 min. after the onset and The 10 min. after the end respectively, of tachycardia. vertical I-shaped bars depict the standard deviation of the mean. cult to ascertain whether reserpine directly interferes with myocardial contractile force to produce pulsus alternans during tachycardia through its deleterious effect on the myocardium or indirectly through the depletion of myocarIn the present study, dial catecholamines. when a single dose (0.5 or 1 mg./kg.) of reserpine was given to the animals approximately 24 hours prior to the experiments, the histologic examination of the heart failed to demonstrate apparent myocardial damage due to the drug. Moreover, the intravenous administration of isoproterenol or epinephrine (1 Mg./kg.) resulted in a transient disappearance of p&us alternans while it increased mean arterial pressure and myocardial contractile force, and decreased left atria1 pressure. On cessation of tachycardia in control dogs, both mean arterial pressure and cardiac output increased markedly and suddenly before they recovered to controls. On the other hand, in reserpinized animals, both mean arterial pressure and cardiac output recovered very gradually
i to 10 minutes, ‘l’hcre was no evidence hyperemia.” Myocardial conof “reactive tractile force decreased markedly before gradual recovery to control, although pulsus alternans disappeared at the end of tachycardia. It is diflicult to explain the absence of reactive hyperemia in reserpinized animals. It is tempting to speculate that, in reserpinized dogs, the blood vessels were already markedly dilated by reserpine prior to the induction of tachycardia. Hence, the tissue hypoxia secondary to the decrease in cardiac output during tachycardia is not effective in the further dilatation of the vessels. Another explanation may be that myocardial contractile force is markedly impaired in reserpinized anima!s, so even after the end of tachycardia the myocardium will not be able to function to increase cardiac output and mean arterial pressure. Tachycardia firr SP probably aggravates an already depleted myocardial reserve. within
SUMMARY Hemodynamic effects of atria1 and ventricular tachycardia in control dogs were compared with those in reserpinized dogs. In control dogs, at the onset of tachycardia, mean arterial pressure, cardiac output and myocardial contractile force decreased suddenly and then improved fairly soon toward control values. Myocardial contractile force generally increased above control. On the other hand, in reserpinized dogs, initial, abrupt decreases in mean arterial pressure, cardiac output and myocardial contractile force were followed by further decreases in these parameters before stabilizing at lower levels than those observed in control In addition, dogs. tachycardia was always accompanied by pulsus alternans with the alternation of the amplitude of myocardial contractile force. On cessation of tachycardia in control dogs, both mean arterial pressure and cardiac output increased suddenly and markedly before their recovery to controls, whereas in reserpinized dogs, both mean arterial pressure and cardiac output recovered very slowly without showing a phase of “reactive hyperemia.” The causative mechanisms responsible for the present observations are discussed.
The author is indebted to Dr. H. A. Strade of Organon, Inc., West Orange, N. J. and Dr. H. G. Schoepke of Abbott Laboratories, North Chicago, Ill., and to Dr. W. E. Wagner of Ciba Pharmaceutical THE AMERICAN JOURNALOF CARDIOLOGY
Tachycardia,
Reserpine
and Cardiovascular
Co. for generous supplies of sodium heparin solutions and reserpine. The author also acknowledges the technical assistance of Z. R. Wiliams and R. Rollins.
REFERENCES 1. NAKANO, J. et al.
2.
3.
4.
5.
Effect of ventricular tachycardia and arteriovenous fistula on catecholamine blood level. Am. J. Physiol., 200: 413, 1961. NAKANO, J. Effects of atria1 and ventricular tachycardias on the cardiovascular dynamics. Am. J. Physiol., 206: 547, 1964. NAKANO, J. and DE SCHRYVER, C. Effect of changes in carotid sinus pulse pressure on catecholamine blood levels. Am. J. Physiol., 204: 467, 1963. CARLSSON, A., ROSENGREN, E., BERTLER, A. and NILSSON, J. Effect of reserpine on the metabolism of catecholamines. In: Psychotropic Drugs, p. 363. Edited by GARATTINI, S. and GHETTI, V. Amsterdam, 1957. Elsevier. LEE, W. C. and SHIDEMAN,F. E. Role of myocardial catecholamines in cardiac contractility. Science, 129: 967, 1959.
JULY 1961
Dynamics
93
6. NAYLER, W. G. A direct effect of reserpine on ventricular contractility. J. Pharmacol. @ Exper. Therap., 139: 222, 1963. 7. SHIPLEY, R. E. and WILSON, C. An improved recording rotameter. Proc. Sot. Exper. Biol. @ Med., 78: 724, 1951. 8. COTTEN, M. DEV. and BAY, E. Direct measutement of changes in cardiac contractile force. Am. J. Physiol., 187: 122, 1956. 9. SAUNDERS, D. E. and ORD, J. W. The hemodynamic effects of paroxysmal supraventricular tachycardia in patients with the Wolff-ParkinsonWhite syndrome. Am. J. Cordial., 9: 223, 1962. 10. ELLIS, C. H. Antagonism of drug-induced pulsus alternans in dogs. Am. J. Physiol., 199: 167, 1960. 11. MITCHELL, J. H., SARNOFF, S. J. and SONNENBLICK, E. H. The dynamics of pulsus alternans: Alternating end-diastolic fiber length as a regulating factor. J. Clin. Invest., 42: 55, 1963. 12. ZAMIS, E. Reserpine-induced Nature, 192: 521, 1961.
circulatory
failure.
Tachycardia
Dynamics in Dogs*
JIRO NAKANO, M.D. Oklahoma
City, Oklahoma
GENTLY it was observed that atria1 and ventricular tachycardia resulted in increased sympathoadrenal activity by decreasing mean arterial and pulse pressures.1-3 It has been known that reserpine depletes catecholamine contents of various tissues495 and decreases myocardial contractile force.5,s The present study was undertaken to compare the effect of tachycardia on the cardiovascular dynamics in control animals with that in reserpinized animals.
recorded continuously with an Electronics for Medicine recorder (Model DR8). Atria1 or ventricular tachycardia with rates ranging from 200 to 240 beats/min. was induced with a Crass stimulator (Model S4). D.C. stimuli of about 5 msec. in duration and of liminal intensity were applied to the left atria1 appendage or to the apical region of the left ventricle through two fish-hook electrodes.
RESULTS Control Dogs: The results observed were consistent in all experiments. Tracings of representative experiments in control and reserpinized dogs are illustrated in Figures 1 and 2. The results of the hemodynamic effects of ventricular tachycardia with equivalent rates in two groups of dogs are summarized in Figure 3. In control dogs, as shown in Figure l,A and B, the induction of tachycardia resulted in sudden reductions in mean arterial pressure, cardiac output and myocardial contractile force, while left and right atria1 pressures increased significantly. Within one to two minutes. after the onset, mean arterial pressure and cardiac output returned toward control values (Fig. 1). Left and right atria1 pressures remained elevated. Usually mean arterial pressure and cardiac output stabilized at levels significantly below controls, while myocardial contractile force increased considerably above control value and stabilized at that level. On termination of tachycardia, both mean arterial pressure and cardiac output increased markedly above control levels, whereas myocardial contractile force, left atria1 pressure and right atria1 pressure returned to controls rather abruptly. Within two to three minutes after the end of
METHODS Thirty dogs weighing between 20.5 and 25.0 kg. were anesthetized with intravenous administration of sodium pentobarbital (20 to 30 mg./kg.). In 15 dogs, a single dose (0.5 to 1 mg./kg.) of reserpine was given intravenously about 24 hours prior to the experiment. The left hemithorax was opened under artificial respiration. The pericardium was incised and the heart suspended in a pericardial cradle. The method used to measure continuously cardiac output (minus coronary blood flow) with a ShipleyWilson rotamete? was a procedure previously described.l12 In all experiments, 5 mg./kg. of sodium heparin was administered intravenously before cannulation of the vessels and 2.5 mg./kg. was repeated every half hour. Mean arterial pressure and left and right atria1 pressures were measured continuously with Statham pressure transducers (P23AA) connected to catheters placed, respectively, in the root of aorta, in the left atrium through a pulmonary vein and in the right atrium through a branch of the right external jugular vein. Continuous measurement of heart rate and myocardial contractile force were made with an Electronics for Medicine tachometer and by a Walton-Brodie strain gauge arch,8 which was sutured directly to the left ventricular muscle. All the hemodynamic parameters, except heart rate, were
* From the Department of Pharmacology, University of Oklahoma School of Medicine, Oklahoma City, Okla. This work was supported in part by research grants (HE-07334, HE-08057 and H-31 11) from the U. S. Public Health Service. JULY
1964
89
‘EWWX,.,AR
133
‘ACHYCARDIC
FIG. 1. X, effects of \wtricular tachycardia OII mywardial contractllc iorcc (MCF 1, lcfr atria1 pressure (LAP), and mean arterial blood pressure (MABP) in a control dog. B. effects of ventricular tachycardia on left atria1 pressure (LAP), right atria1 pressure (RAP), cardiac output (CO) and mean arterial blood pressure (MABP) in a control dog. C, effects of ventricular tachycardia on left atria1 pressurr (LAP), mean arterial blood pressure (MABP). cardiac output (CO) and myocardial contractile force (MCF) in a reswpinizc-d dog.
tachycardia, all hemodynamic parameters returned to control values. Reser@inized Dogs: On the other hand, upon the onset of tachycardia in reserpinized dogs, mean arterial pressure, cardiac output and myocardial contractile force decreased suddenly, and then decreased further very slowly before stabilizing at levels considerably below controls (Fig. IC and 2). Left atria1 pressure increased rather suddenly at the onset and remained at that level. During tachycardia, contractile force was always alternated in its amplitude one beat from another, synchronizing with alternations of arterial pressure pulse; i.e., pulsus alternans. At cessation of tachycardia, cardiac output, myocardial contractile force and mean arterial pressure increased
gradually toward control values. Myocardial contractile force usually decreased further before complete recovery, although pulsus alternans as well as alternations of amplitude of contractile force disappeared at the end of tachycardia. Occasionally, mean arterial pressure increased over control level three to eight minutes after the end of tachycardia. As shown in Figure 2, when a single dose (1 pg./kg.) of isoproterenol or epinephrine was given intravenously about three minutes after the induction of tachycardia in reserpinized dogs, pulsus alternans and coinciding alternations of myocardial contractile force disappeared for approximately four minutes. In addition, during this period, the drugs also increased mean arterial pressure and myocardial contractile force and decreased left THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Tachycardia,
Reserpine
and
Cardiovascular
Dynamics
71
FIG. 2.
Effects of atria1 tachycardia on electrocardiogram (EGG), left atria1 pressure (LAP), aortic blood pressure contractile force (MCF) in a reserpinized dog. Atria1 tachycardia was induced between the first and third vertical arrows. At the second arrow, isoproterenol (1 pg. /kg.) was given intravenously. ( ABP), and myocardial
atria1 pressure, whereas the electrocardiogram revealed a significant elevation of S-T segment and reversal of T wave. DISCUSSION
From the present study it is clear that the evolutional changes following the beginning and the end of atria1 or ventricular tachycardia in control dogs are considerably different from those in reserpinized dogs (Fig. 3). In control dogs, following a short phase of sudden decreases on the onset of tachycardia, mean arterial pressure, cardiac output and myocardial contractile force improve gradually toward control values with myocardial contractile force actually increasing above control. On the other hand, in reserpinized dogs, the compensatory hemodynamic adjustments subsequent to the onset of tachycardia are not observed. Initial, abrupt decreases in mean arterial pressure, cardiac output and myocardial contractile force are followed by further gradual decreases in these parameters before stabilizing at lower levels than those observed in control dogs. In addiJULY
1964
tion, in reserpinized dogs, tachycardia always results in pulsus alternans synchronous with the alternation of the amplitude of myocardial contractile force (Fig. 2). The absence of the hemodynamic improvements in the earlier period of tachycardia already mentioned may be most likely due to the lack of or to insufficient participation of sympathoadrenal activity, since reserpine is known to deplete catecholamine contents of various tissues4 The causative mechanism of pulsus alternans has not been adequately elucidated as yet, although it has been known to occur under various pathophysiologic conditions which may interfere with ventricular function directly or indirectly.+” Lee and Shidemanb and Nayler6 showed that reserpine markedly decreases myocardial contractile force in the cat papillary muscles and toad ventricle, as the catecholamine contents of the myocardium decreased or were depleted markedly.6 Recently, %amiP observed that large doses of reserpine caused irreversible extensive myocardial damage through some unknown mechanism. It is rather diffi-
CONTROL DOGS
(n=lO)
HEART RATE beatVmin
~WI-
MEAN ARTERIAL PRESSURE
2ce
m-
r-s-x-
RESERFlNlZED
DOGS(n=lO) -
+
+
C TI RRI
Ra
0
mm4 0
CARDIAC OUTPUT a%
l@xlOL
l-7-WI
+
C TI RRI
-&-x4+ *
Rz
C TI T2 RI Q
FIG. 3. Effects of ventricular tachycardia on mean arterial pressure, cardiac output and myocardial contractile force in control dogs and reserpinized dogs. The bars represent the average values. C = control value. T1 and RI = values obtained immediately after the onset and end of ventricular tachycardia, respectively. Tt and RS = values obtained 3 min. after the onset and The 10 min. after the end respectively, of tachycardia. vertical I-shaped bars depict the standard deviation of the mean. cult to ascertain whether reserpine directly interferes with myocardial contractile force to produce pulsus alternans during tachycardia through its deleterious effect on the myocardium or indirectly through the depletion of myocarIn the present study, dial catecholamines. when a single dose (0.5 or 1 mg./kg.) of reserpine was given to the animals approximately 24 hours prior to the experiments, the histologic examination of the heart failed to demonstrate apparent myocardial damage due to the drug. Moreover, the intravenous administration of isoproterenol or epinephrine (1 Mg./kg.) resulted in a transient disappearance of p&us alternans while it increased mean arterial pressure and myocardial contractile force, and decreased left atria1 pressure. On cessation of tachycardia in control dogs, both mean arterial pressure and cardiac output increased markedly and suddenly before they recovered to controls. On the other hand, in reserpinized animals, both mean arterial pressure and cardiac output recovered very gradually
i to 10 minutes, ‘l’hcre was no evidence hyperemia.” Myocardial conof “reactive tractile force decreased markedly before gradual recovery to control, although pulsus alternans disappeared at the end of tachycardia. It is diflicult to explain the absence of reactive hyperemia in reserpinized animals. It is tempting to speculate that, in reserpinized dogs, the blood vessels were already markedly dilated by reserpine prior to the induction of tachycardia. Hence, the tissue hypoxia secondary to the decrease in cardiac output during tachycardia is not effective in the further dilatation of the vessels. Another explanation may be that myocardial contractile force is markedly impaired in reserpinized anima!s, so even after the end of tachycardia the myocardium will not be able to function to increase cardiac output and mean arterial pressure. Tachycardia firr SP probably aggravates an already depleted myocardial reserve. within
SUMMARY Hemodynamic effects of atria1 and ventricular tachycardia in control dogs were compared with those in reserpinized dogs. In control dogs, at the onset of tachycardia, mean arterial pressure, cardiac output and myocardial contractile force decreased suddenly and then improved fairly soon toward control values. Myocardial contractile force generally increased above control. On the other hand, in reserpinized dogs, initial, abrupt decreases in mean arterial pressure, cardiac output and myocardial contractile force were followed by further decreases in these parameters before stabilizing at lower levels than those observed in control In addition, dogs. tachycardia was always accompanied by pulsus alternans with the alternation of the amplitude of myocardial contractile force. On cessation of tachycardia in control dogs, both mean arterial pressure and cardiac output increased suddenly and markedly before their recovery to controls, whereas in reserpinized dogs, both mean arterial pressure and cardiac output recovered very slowly without showing a phase of “reactive hyperemia.” The causative mechanisms responsible for the present observations are discussed.
The author is indebted to Dr. H. A. Strade of Organon, Inc., West Orange, N. J. and Dr. H. G. Schoepke of Abbott Laboratories, North Chicago, Ill., and to Dr. W. E. Wagner of Ciba Pharmaceutical THE AMERICAN JOURNALOF CARDIOLOGY
Tachycardia,
Reserpine
and Cardiovascular
Co. for generous supplies of sodium heparin solutions and reserpine. The author also acknowledges the technical assistance of Z. R. Wiliams and R. Rollins.
REFERENCES 1. NAKANO, J. et al.
2.
3.
4.
5.
Effect of ventricular tachycardia and arteriovenous fistula on catecholamine blood level. Am. J. Physiol., 200: 413, 1961. NAKANO, J. Effects of atria1 and ventricular tachycardias on the cardiovascular dynamics. Am. J. Physiol., 206: 547, 1964. NAKANO, J. and DE SCHRYVER, C. Effect of changes in carotid sinus pulse pressure on catecholamine blood levels. Am. J. Physiol., 204: 467, 1963. CARLSSON, A., ROSENGREN, E., BERTLER, A. and NILSSON, J. Effect of reserpine on the metabolism of catecholamines. In: Psychotropic Drugs, p. 363. Edited by GARATTINI, S. and GHETTI, V. Amsterdam, 1957. Elsevier. LEE, W. C. and SHIDEMAN,F. E. Role of myocardial catecholamines in cardiac contractility. Science, 129: 967, 1959.
JULY 1961
Dynamics
93
6. NAYLER, W. G. A direct effect of reserpine on ventricular contractility. J. Pharmacol. @ Exper. Therap., 139: 222, 1963. 7. SHIPLEY, R. E. and WILSON, C. An improved recording rotameter. Proc. Sot. Exper. Biol. @ Med., 78: 724, 1951. 8. COTTEN, M. DEV. and BAY, E. Direct measutement of changes in cardiac contractile force. Am. J. Physiol., 187: 122, 1956. 9. SAUNDERS, D. E. and ORD, J. W. The hemodynamic effects of paroxysmal supraventricular tachycardia in patients with the Wolff-ParkinsonWhite syndrome. Am. J. Cordial., 9: 223, 1962. 10. ELLIS, C. H. Antagonism of drug-induced pulsus alternans in dogs. Am. J. Physiol., 199: 167, 1960. 11. MITCHELL, J. H., SARNOFF, S. J. and SONNENBLICK, E. H. The dynamics of pulsus alternans: Alternating end-diastolic fiber length as a regulating factor. J. Clin. Invest., 42: 55, 1963. 12. ZAMIS, E. Reserpine-induced Nature, 192: 521, 1961.
circulatory
failure.