Cardiovascular Research, 1976, 10, 385-388.
Coronary occlusion before, during, and after strenuous exercise' P E T E R L . T H O M P S O N ~and B E R N A R D L O W N
From the Cardiovascular Laboratories, Departrnent of Nutrition, Harvard School of Public Health, Boston, Mass, U S A
I n earlier reports from this laboratory, the effect of ligation; this period varies from 2-6min. It strenuous exercise on the dog with acute coronary may be that exercise stress is arrhythmogenic artery occlusion has been studied. Kaplinsky only when carried out during this discrete interet af (1 968) subjected dogs to frequent treadmill val of electrical instability. To test this possirunning until exhaustion beginning 3 d after bility the present study was designed to compare coronary ligation. No sudden death or signifi- the effects of exercise performed during, as well cant arrhythmias were observed. After 3 weeks as immediately before and immediately after of daily exercise, the animals demonstrated the coronary artery occlusion. benefits of a programme of exercise conditioning. Thompson et al (1973) exercised dogs to the point of exhaustion within 1 h after coronary Materials and methods occlusion; once again, arrhythmias were absent. Compared to a matched control group, there Healthy mongrel dogs weighing 18-30 kg were was no difference in the prevalence of aneurysm prepared as previously described (Thompson et al. formation, of cardiac rupture or of infarct size 1973). The following procedures were common to measured at necropsy. The failure of strenuous both experiments. exercise to provoke VF or other ventricular arrhythmias was unexpected. I n dogs there is Thoracotomy but a brief period of susceptibility to VF follow- Under pentobarbital anaesthesia with assisted ing left-anterior descending coronary artery respiration, the thorax was opened through the 4th left intercostal space. The left anterior descending ' Supported by Grants No. HL-5242 and HL-07776 from the National coronary artery was dissected free at the level of the Heart and Lung Institute of the National Institutes of Health, US left atrial appendagc. A silastic cuff enclosing an Public Health Service. inflatable balloon was positioned around the artery, Reprint requests lo B.L., Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston. Massacncircling but not constricting it. A catheter attached chusetts 021 15, USA. to the balloon was brought to the surface at the Present address: Coronary Care Unit, Perth Medical Centre. Shennape of the neck. ton Park, Western Australia.
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A U T H O R S ' S Y N O P S I S Groups of dogs were exercised immediately before, and immediately after occlusion of the left anterior descending coronary artery. Coronary occlusion by a staged procedure resulted in a low mortality and rare ventricular ectopic beats. The combination of simultaneous exercise with coronary occlusion reproducibly provoked ventricular fibrillation (VF). Exercise before and after occlusion frequently produced ventricular tachycardia but no VF. The risk of major arrhythmias was related to the peak heart rate resulting from the exercise.
386 Thonipson and L o w Staged coronary occlusion Occlusion of the left anterior descending coronary artery was achieved by intermittent inflation and deflation of the implanted balloon. Saline was injected into the balloon according to the following schedule: I min inflation (I), 1 rnin deflation (D): 2min I, 2 min D, 5 rnin I, 1 rnin D; and then finally permanent inflation. Duration of the procedure was 12 min; the immediate mortality was less than 5%. During coronary occlusion the electrocardiogram was monitored from silver electrodes strapped firmly to the shaved chest wall.
Exercise Dogs were exercised by running on a high speed treadmill. Leashes to prevent forward and backward movement were attached to the dog with a padded collar. Exercise started at 4 mph at 10% grade; the grade was increased by 10% and the speed by 1 mph each 5 min. The end point of exercise was either a major arrhythmia or exhaustion.
I Control group Control animals had staged coronary occlusion in the awake state. After coronary occlusion the dogs were led to a cage and the electrocardiogram was monitored continuously for the subsequent 24 h or until the disappearance of the multifocal ventricular tachycardia which follows canine coronary occlusion.
Early mortality (0-60 min) The deaths in each group are shown in Fig. I . Staged coronary occlusion performed in tne control group while resting resulted in only one early death (at 5 rnin). Exercise immediately after coronary occlusion (CO before EX) did not affect early mortality. In the group exercised immediately before coronary occlubion (CO after EX), there were three early deaths (at 1, 4, and 15 min). In the group of 10 dogs with coronary occlusion effected while the animal was exercising (CO during EX), seven dogs died early, five within the first minute. All early deaths were due to ventricular fibrillation.
Deaths 1st h Deaths I-24h
co
CO durinq EX
I
0 2
4
b
8 1 0
No ofanimals
. I Timing o/ deaths in Jortr groups o j 10 clogs (CO -coronary occlusion, EX -exercise). F IG
2 Occlrrsiotr hcqiwe exercise (CO hifore E X ) Dogs in this group had coronary occlusion performed while standing or sitting on the treadmill
with the motor running. Exercise was begun immediately after the final coronary occlusion. At the end of exercise the dogs were treated in the same manner as the control group. 3 Occlusion ufter exercise (CO ujter EX)
Dogs in this group were exercised on the treadmill to the point of exhaustion; then, while still standing on the treadmill, coronary occlusion was performed. When coronary occlusion was completed the animals were treated in the same manner as the control group. 4
O c c h i o n during exercise (CO during E X )
Dogs in this group were exercised on the treadmill for 5 min. While exercise continued coronary occlusion was begun. The surviving animals were subsequently treated in the same manner as the control group.
Late mortality (1-24 h) In the subsequent 24 h, there was a low mortality in the control group (one death in nine survivors) and a high mortality in the animals who had exercised about the time of coronary occlusion (seven deaths in 20 survivors). Thus exercise affected late mortality, but there was insufficient animals in each group t o assess the importance of the timing of the exercise. Arrhythmias Coronary occlusion in the control animals resulted in rare ventricular premature beats. In contrast, exercise before or after coronary occlusion frequently evoked rapid ventricular tachycardia. A n example is shown in Fig. 2; this
Downloaded from by guest on November 2, 2015
Experimental design There were 40 dogs in four groups of 10.
Results
387 Coronary occlusion and exerci i e No VT/VF (n = 271
- n12i m
14 min
t IS0
*O
o Control doqs
Exercised doqr
I 8 min
.. ....... ..... P 0
100
2 Dog exercised immediately after completion of’staged coronary artery occlirsion. Rapid ventricular tachycardia at 14 rnin, with spontaneous reversion.
F I G . 4 Comparison of heart rate immediately before and after coronary occlusion. VT ventricular tachyccirdia; V F veiitricirlar fibrillation.
arrhythmia was frequently self-reverting. In the animals exercising at the time of coronary occlusion, ventricular fibrillation was the outcome in seven of 10 animals (Fig. 3).
significant difference P i0.05. N o features of the ST segment, T-wave, or QT interval were predictive of arrhythmias.
FIG.
~
Discussion Earlier attempts to produce a laboratory model of exercise induced sudden death were unsuccessmill exercise. Ventricitlar tachycardia within 9 s and ful, even when the exercise was performed within ventricirlar fibrillation at 16 s. I h of coronary occlusion (Kaplinsky et af, 1968; Thompson et al, 1973). The present study demonstrated that the risk of exercise after Factors associated with arrhythmias coronary artery occlusion is closely related to The most significant determinant of a major the timing of exercise, being most lethal when arrhythmia was the heart rate evoked by exer- the exercise and coionary occlusion are simulcise: when it exceeded 200/min, ventricular taneous. Stage coronary occlusion performed in tachycardia or fibrillation almost invariably the resting state caused only one immediate resulted (Fig. 4). The mean heart rate of those death. Exercise immediately before and after dogs who had a major arrhythmia was 2181-22 coronary occlusion caused a moderate increase beats/min (mean &SD) and in those who did in mortality, but when the coronary artery not, it was 176+16 beats/min. This was a closure occurred during exercise, seven of the FIG.
3 Coronary occlusion perjormed during tread-
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Effect of coronary occlusion on exercise tolerance Despite the presence of recent coronary occlusion, exercise performances was unaffected in most animals. In those animals who exercised before coronary occlusion, duration of exercise was 17.514.5 min: in those exercised after coronary occlusion it was 18.8-18.6 min (despite the arrhythmias recorded); in those who survived coronary occlusion during exercise it was 23 3 2.4 min.
388 Thompson and Lown demonstrated ventricular ectopics in their resting electrocardiogram. With submaximal exercise 28.6 developed ectopics when exercise was maximal and higher heart rates were achieved, 49.4 % exhibited ventricular arrhythmias. In animal studies, Kaplinsky et a1 (1972), demonstrated that the provocation of arrhythmia by cardiac pacing in dogs with coronary ligations was directly related to the frequency of stimulation. Thus, the hazard of exercise relates to the occurrence of a critical degree of coronary arterial narrowing or obstruction developed during acute stress of exercise as well as to the degree of cardiac rate acceleration achieved. We wish to thank Mr Sam Rivers and Mr George Lebrun for skilled technical assistance.
References Blackburn, H., Taylor, H. L., Hamrell, B., Buskirk. E. Nicholas, W. C., and Thorsen, R. D. (1973). Premature ventricular complexes induced by exercise stress testing: their frequency and response t o physical conditioning. American Joiirrial of Cardiology, 31, 441-449. Chadda, K. D.. Banka, V. S.,and Helfant, R. H. (1974). Rate dependent ventricular ectopia following acute coronary occlusion. The concept of an optimal anti-arrhythniic heart rate. Circulation, 49, 654-658. Jelinek, M. V., and Lown, B. (1974). Exercise stress testing for exposure of cardiac arrhythmia. Progress in Cardiovascular Disease, 16, 497-522. Kaplinsky, E., Hood. W. B.. Jr, McCarthy, B., McCombs, H. L., and Lown, B. (1968). Erects of physical training in dogs with coronary artery ligation. Circulation. 37, 556565.
Kaplinsky, E., Yahini, J. H., and Neufeld, H. N. (1972). On the mechanism of sustained ventricular arrhythmias associated with acute myocardial infarction. Cardiovascular Research, 6, 135-142. Kent, K. M.. Smith, E. R., Redwood, D. R., and Epstein, S. E. (1972). The deleterious electrophysiologic effects produced by increasing heart rate during experimental coronary occlusion. Clinical Research, 20, 379. Maroko. P. R., Kjekshus, J. K., Sobel, B. E., Watanabe, T., Covell, J . W., Ross, J., Jr, and Braunwald, E. (1971). Factors influencing infarct size following experimental coronary artery occlusions. Circulation, 43, 67-82. Rochmis, P., and Blackburn, H. (1971). Exercise tests: A survey of procedures, safety, and litigation experience in approximately 170,000 tests. Journal of the American Medical Association, 217, 1061-1066. Scherlag, B. J.. Helfant, R. H., Haft, J. I., and Damato, A. N. ( I 970). Electrophysiology underlying ventricular arrhythmias due to coronary ligation. American Journal of Physiology, 219, 1665-1671. Thompson, P. L., Jenzer, H. R., Lown, B., and Lohrbauer, L. A. (1973). Exercise during acute myocardial infarction: an experimental study. Cardiovascular Research, 7, 642-
648.
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10 animals died almost instantaneously in ventricular fibrillation. Major ventricular arrhythmias were frequent in all the animals exercised close to coronary occlusion, in contrast to control animals who had only infrequent ventricular premature beats. The occurrence of ventricular arrhythmias in the exercised dogs appeared to depend on the heart rate generated by the exercise. Dogs with a peak heart rate in excess of 200/min at the time of coronary occlusion were at greatly increased risk of ventricular tachycardia or fibrillation (Fig. 4). This is in keeping with recent observations that increasing heart rate will precipitate arrhyrhmias in the animal with acute coronary occlusion (Scherlag et al, 1970; Kent et al, 1972; Chadda et al, 1974). The occurrence of arrhythmia may be a direct electrophysiological consequence of the tachycardia which accentuates the inhomogeneity of refractory period durations in the ischaemic tissue; or it may be an indirect result of an increased mass of ischaemic and electrically unstable myocardium (Maroko et al, 1971). The implications of these animal experiments for the patient with coronary artery disease must be guarded (Thompson et al, 1973). However, it accords with the clinical observation of the safety of exercise stress testing in patients with coronary heart disease (CHD). An extensive review of mortality and morbidity following exercise in 73 centres in the United States has been reported by Rochmis and Blackburn (1971). There were only 16 deaths within 24 h after performance of 170 OOO exercise tests - a mortality rate of one per 10 OOO tests. At the Cardiovascular Laboratories of the Harvard School of Public Health, where maximal exercise stress testing is conducted, no fatalities occurred after 4500 tests; a majority conducted among patients with CHD. It may be that VF is precipitated only if major coronary arterial closure or spasm coincides with the imposition of a significant exercise stress. Clinical experience is in agreement with the findings in this study relating peak heart rate to the provocation of ventricular arrhythmia (Jelinek and Lown, 1974). Blackburn et a1 (1973) subjected 196 normals with risk factors for CHD to exercise. Of this group, 3.0%
Coronary occlusion before, during, and after strenuous exercise' P E T E R L . T H O M P S O N ~and B E R N A R D L O W N
From the Cardiovascular Laboratories, Departrnent of Nutrition, Harvard School of Public Health, Boston, Mass, U S A
I n earlier reports from this laboratory, the effect of ligation; this period varies from 2-6min. It strenuous exercise on the dog with acute coronary may be that exercise stress is arrhythmogenic artery occlusion has been studied. Kaplinsky only when carried out during this discrete interet af (1 968) subjected dogs to frequent treadmill val of electrical instability. To test this possirunning until exhaustion beginning 3 d after bility the present study was designed to compare coronary ligation. No sudden death or signifi- the effects of exercise performed during, as well cant arrhythmias were observed. After 3 weeks as immediately before and immediately after of daily exercise, the animals demonstrated the coronary artery occlusion. benefits of a programme of exercise conditioning. Thompson et al (1973) exercised dogs to the point of exhaustion within 1 h after coronary Materials and methods occlusion; once again, arrhythmias were absent. Compared to a matched control group, there Healthy mongrel dogs weighing 18-30 kg were was no difference in the prevalence of aneurysm prepared as previously described (Thompson et al. formation, of cardiac rupture or of infarct size 1973). The following procedures were common to measured at necropsy. The failure of strenuous both experiments. exercise to provoke VF or other ventricular arrhythmias was unexpected. I n dogs there is Thoracotomy but a brief period of susceptibility to VF follow- Under pentobarbital anaesthesia with assisted ing left-anterior descending coronary artery respiration, the thorax was opened through the 4th left intercostal space. The left anterior descending ' Supported by Grants No. HL-5242 and HL-07776 from the National coronary artery was dissected free at the level of the Heart and Lung Institute of the National Institutes of Health, US left atrial appendagc. A silastic cuff enclosing an Public Health Service. inflatable balloon was positioned around the artery, Reprint requests lo B.L., Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston. Massacncircling but not constricting it. A catheter attached chusetts 021 15, USA. to the balloon was brought to the surface at the Present address: Coronary Care Unit, Perth Medical Centre. Shennape of the neck. ton Park, Western Australia.
Downloaded from by guest on November 2, 2015
A U T H O R S ' S Y N O P S I S Groups of dogs were exercised immediately before, and immediately after occlusion of the left anterior descending coronary artery. Coronary occlusion by a staged procedure resulted in a low mortality and rare ventricular ectopic beats. The combination of simultaneous exercise with coronary occlusion reproducibly provoked ventricular fibrillation (VF). Exercise before and after occlusion frequently produced ventricular tachycardia but no VF. The risk of major arrhythmias was related to the peak heart rate resulting from the exercise.
386 Thonipson and L o w Staged coronary occlusion Occlusion of the left anterior descending coronary artery was achieved by intermittent inflation and deflation of the implanted balloon. Saline was injected into the balloon according to the following schedule: I min inflation (I), 1 rnin deflation (D): 2min I, 2 min D, 5 rnin I, 1 rnin D; and then finally permanent inflation. Duration of the procedure was 12 min; the immediate mortality was less than 5%. During coronary occlusion the electrocardiogram was monitored from silver electrodes strapped firmly to the shaved chest wall.
Exercise Dogs were exercised by running on a high speed treadmill. Leashes to prevent forward and backward movement were attached to the dog with a padded collar. Exercise started at 4 mph at 10% grade; the grade was increased by 10% and the speed by 1 mph each 5 min. The end point of exercise was either a major arrhythmia or exhaustion.
I Control group Control animals had staged coronary occlusion in the awake state. After coronary occlusion the dogs were led to a cage and the electrocardiogram was monitored continuously for the subsequent 24 h or until the disappearance of the multifocal ventricular tachycardia which follows canine coronary occlusion.
Early mortality (0-60 min) The deaths in each group are shown in Fig. I . Staged coronary occlusion performed in tne control group while resting resulted in only one early death (at 5 rnin). Exercise immediately after coronary occlusion (CO before EX) did not affect early mortality. In the group exercised immediately before coronary occlubion (CO after EX), there were three early deaths (at 1, 4, and 15 min). In the group of 10 dogs with coronary occlusion effected while the animal was exercising (CO during EX), seven dogs died early, five within the first minute. All early deaths were due to ventricular fibrillation.
Deaths 1st h Deaths I-24h
co
CO durinq EX
I
0 2
4
b
8 1 0
No ofanimals
. I Timing o/ deaths in Jortr groups o j 10 clogs (CO -coronary occlusion, EX -exercise). F IG
2 Occlrrsiotr hcqiwe exercise (CO hifore E X ) Dogs in this group had coronary occlusion performed while standing or sitting on the treadmill
with the motor running. Exercise was begun immediately after the final coronary occlusion. At the end of exercise the dogs were treated in the same manner as the control group. 3 Occlusion ufter exercise (CO ujter EX)
Dogs in this group were exercised on the treadmill to the point of exhaustion; then, while still standing on the treadmill, coronary occlusion was performed. When coronary occlusion was completed the animals were treated in the same manner as the control group. 4
O c c h i o n during exercise (CO during E X )
Dogs in this group were exercised on the treadmill for 5 min. While exercise continued coronary occlusion was begun. The surviving animals were subsequently treated in the same manner as the control group.
Late mortality (1-24 h) In the subsequent 24 h, there was a low mortality in the control group (one death in nine survivors) and a high mortality in the animals who had exercised about the time of coronary occlusion (seven deaths in 20 survivors). Thus exercise affected late mortality, but there was insufficient animals in each group t o assess the importance of the timing of the exercise. Arrhythmias Coronary occlusion in the control animals resulted in rare ventricular premature beats. In contrast, exercise before or after coronary occlusion frequently evoked rapid ventricular tachycardia. A n example is shown in Fig. 2; this
Downloaded from by guest on November 2, 2015
Experimental design There were 40 dogs in four groups of 10.
Results
387 Coronary occlusion and exerci i e No VT/VF (n = 271
- n12i m
14 min
t IS0
*O
o Control doqs
Exercised doqr
I 8 min
.. ....... ..... P 0
100
2 Dog exercised immediately after completion of’staged coronary artery occlirsion. Rapid ventricular tachycardia at 14 rnin, with spontaneous reversion.
F I G . 4 Comparison of heart rate immediately before and after coronary occlusion. VT ventricular tachyccirdia; V F veiitricirlar fibrillation.
arrhythmia was frequently self-reverting. In the animals exercising at the time of coronary occlusion, ventricular fibrillation was the outcome in seven of 10 animals (Fig. 3).
significant difference P i0.05. N o features of the ST segment, T-wave, or QT interval were predictive of arrhythmias.
FIG.
~
Discussion Earlier attempts to produce a laboratory model of exercise induced sudden death were unsuccessmill exercise. Ventricitlar tachycardia within 9 s and ful, even when the exercise was performed within ventricirlar fibrillation at 16 s. I h of coronary occlusion (Kaplinsky et af, 1968; Thompson et al, 1973). The present study demonstrated that the risk of exercise after Factors associated with arrhythmias coronary artery occlusion is closely related to The most significant determinant of a major the timing of exercise, being most lethal when arrhythmia was the heart rate evoked by exer- the exercise and coionary occlusion are simulcise: when it exceeded 200/min, ventricular taneous. Stage coronary occlusion performed in tachycardia or fibrillation almost invariably the resting state caused only one immediate resulted (Fig. 4). The mean heart rate of those death. Exercise immediately before and after dogs who had a major arrhythmia was 2181-22 coronary occlusion caused a moderate increase beats/min (mean &SD) and in those who did in mortality, but when the coronary artery not, it was 176+16 beats/min. This was a closure occurred during exercise, seven of the FIG.
3 Coronary occlusion perjormed during tread-
Downloaded from by guest on November 2, 2015
Effect of coronary occlusion on exercise tolerance Despite the presence of recent coronary occlusion, exercise performances was unaffected in most animals. In those animals who exercised before coronary occlusion, duration of exercise was 17.514.5 min: in those exercised after coronary occlusion it was 18.8-18.6 min (despite the arrhythmias recorded); in those who survived coronary occlusion during exercise it was 23 3 2.4 min.
388 Thompson and Lown demonstrated ventricular ectopics in their resting electrocardiogram. With submaximal exercise 28.6 developed ectopics when exercise was maximal and higher heart rates were achieved, 49.4 % exhibited ventricular arrhythmias. In animal studies, Kaplinsky et a1 (1972), demonstrated that the provocation of arrhythmia by cardiac pacing in dogs with coronary ligations was directly related to the frequency of stimulation. Thus, the hazard of exercise relates to the occurrence of a critical degree of coronary arterial narrowing or obstruction developed during acute stress of exercise as well as to the degree of cardiac rate acceleration achieved. We wish to thank Mr Sam Rivers and Mr George Lebrun for skilled technical assistance.
References Blackburn, H., Taylor, H. L., Hamrell, B., Buskirk. E. Nicholas, W. C., and Thorsen, R. D. (1973). Premature ventricular complexes induced by exercise stress testing: their frequency and response t o physical conditioning. American Joiirrial of Cardiology, 31, 441-449. Chadda, K. D.. Banka, V. S.,and Helfant, R. H. (1974). Rate dependent ventricular ectopia following acute coronary occlusion. The concept of an optimal anti-arrhythniic heart rate. Circulation, 49, 654-658. Jelinek, M. V., and Lown, B. (1974). Exercise stress testing for exposure of cardiac arrhythmia. Progress in Cardiovascular Disease, 16, 497-522. Kaplinsky, E., Hood. W. B.. Jr, McCarthy, B., McCombs, H. L., and Lown, B. (1968). Erects of physical training in dogs with coronary artery ligation. Circulation. 37, 556565.
Kaplinsky, E., Yahini, J. H., and Neufeld, H. N. (1972). On the mechanism of sustained ventricular arrhythmias associated with acute myocardial infarction. Cardiovascular Research, 6, 135-142. Kent, K. M.. Smith, E. R., Redwood, D. R., and Epstein, S. E. (1972). The deleterious electrophysiologic effects produced by increasing heart rate during experimental coronary occlusion. Clinical Research, 20, 379. Maroko. P. R., Kjekshus, J. K., Sobel, B. E., Watanabe, T., Covell, J . W., Ross, J., Jr, and Braunwald, E. (1971). Factors influencing infarct size following experimental coronary artery occlusions. Circulation, 43, 67-82. Rochmis, P., and Blackburn, H. (1971). Exercise tests: A survey of procedures, safety, and litigation experience in approximately 170,000 tests. Journal of the American Medical Association, 217, 1061-1066. Scherlag, B. J.. Helfant, R. H., Haft, J. I., and Damato, A. N. ( I 970). Electrophysiology underlying ventricular arrhythmias due to coronary ligation. American Journal of Physiology, 219, 1665-1671. Thompson, P. L., Jenzer, H. R., Lown, B., and Lohrbauer, L. A. (1973). Exercise during acute myocardial infarction: an experimental study. Cardiovascular Research, 7, 642-
648.
Downloaded from by guest on November 2, 2015
10 animals died almost instantaneously in ventricular fibrillation. Major ventricular arrhythmias were frequent in all the animals exercised close to coronary occlusion, in contrast to control animals who had only infrequent ventricular premature beats. The occurrence of ventricular arrhythmias in the exercised dogs appeared to depend on the heart rate generated by the exercise. Dogs with a peak heart rate in excess of 200/min at the time of coronary occlusion were at greatly increased risk of ventricular tachycardia or fibrillation (Fig. 4). This is in keeping with recent observations that increasing heart rate will precipitate arrhyrhmias in the animal with acute coronary occlusion (Scherlag et al, 1970; Kent et al, 1972; Chadda et al, 1974). The occurrence of arrhythmia may be a direct electrophysiological consequence of the tachycardia which accentuates the inhomogeneity of refractory period durations in the ischaemic tissue; or it may be an indirect result of an increased mass of ischaemic and electrically unstable myocardium (Maroko et al, 1971). The implications of these animal experiments for the patient with coronary artery disease must be guarded (Thompson et al, 1973). However, it accords with the clinical observation of the safety of exercise stress testing in patients with coronary heart disease (CHD). An extensive review of mortality and morbidity following exercise in 73 centres in the United States has been reported by Rochmis and Blackburn (1971). There were only 16 deaths within 24 h after performance of 170 OOO exercise tests - a mortality rate of one per 10 OOO tests. At the Cardiovascular Laboratories of the Harvard School of Public Health, where maximal exercise stress testing is conducted, no fatalities occurred after 4500 tests; a majority conducted among patients with CHD. It may be that VF is precipitated only if major coronary arterial closure or spasm coincides with the imposition of a significant exercise stress. Clinical experience is in agreement with the findings in this study relating peak heart rate to the provocation of ventricular arrhythmia (Jelinek and Lown, 1974). Blackburn et a1 (1973) subjected 196 normals with risk factors for CHD to exercise. Of this group, 3.0%
