H. L. Stone

The relationship between activity of the autonomic nervous system, myocardial ischemia, and malignant arrhythmias has been investigated in a new experimental preparation for sudden death. Fifty-seven dogs were chronically instrumented and studied under control conditions (n = 15) and 1 month after production of an anterior myocardial infarction (n = 42). The protocol consisted in occluding the left circumflex coronary artery for 2 min, commencing at the last minute of an exercise stress test and extending through the first minute after cessation of exercise. With this protocol, ventricular fibrillation was observed in 40% of normal dogs and 66% of dogs with infarction. In 14 dogs with infarction, left stellectomy reduced the incidence of ventricular fibrillation to zero (p less than .001). The reflex changes in heart rate elicited within the first minute of ischemia during exercise in the animals that survived (from 204 +/- 14 to 198 +/- 31 beats/min, -6) were opposite those in animals that had ventricular fibrillation (from 208 +/- 24 to 229 +/- 30 beats/min, +21) (p less than .05). The ischemia-induced reduction in heart rate despite continuation of exercise suggests the presence in the dogs that survived of active vagal reflexes that may have played an important role in the maintenance of cardiac electrical stability. This preparation has the potential to induce ventricular fibrillation consistently in conscious animals by the interaction of a few clinically relevant factors (acute myocardial ischemia, submaximal exercise and its cessation, sympathetic and vagal reflexes, and heart rate) and offers the possibility of acquiring further insights into the mechanisms of malignant arrhythmias and evaluating novel strategies for targeted prevention.

To explore the possibility that the analysis of autonomic reflexes could identify subgroups at high risk of ventricular fibrillation, we studied chronically instrumented mongrel dogs randomly divided into two groups. Twelve dogs served as controls and 17 were studied 3-4 weeks after anterior wall myocar- dial infarction (MI). After recovery, the dogs were given bolus i.v. injections of phenylephrine, 10 .tg/kg, and nitroprusside, 100 ptg/kg, to raise or lower systolic arterial pressure 30-50 mm Hg. The RR intervals were plotted against the systolic pressure during the preceding beats, and the slope (baroreflex slope) was determined by least-squares-fit linear regression. On a subsequent day, the left circumflex coronary artery was occluded for 2 minutes, beginning with the last minute of an exercise stress test and continuing for 1 minute after the cessation of exercise (MI group only). The dogs could be divided into two groups based on their response to this test; 11 dogs (65%) had ventricular fibrillation (susceptible), whereas six dogs (35%) did not (resistant). The baroreflex slope (control 20.49 8.59; resistant 10.95 4.68; susceptible 4.60 + 1.77 msec/mm Hg) and the heart rate response to a 30-mm Hg increase in arterial pressure (control -56.5 + 14.8; resistant -40.0 12.2; susceptible -12.9 5.0 beats/min) for the susceptible dogs were signifi- cantly different from those of the control and resistant dogs. This may indicate that the resistant dogs have a greater capability to activate strong vagal reflexes, which reduce vulnerability to ventricular fibrillation. We conclude that anterior wall MI significantly attenuates the baroreceptor reflex control of heart rate and that analysis of the heart rate response to arterial pressure increases allows identification of subgroups of dogs at higher risk for ventricular fibrillation. A prospective study in patients with MI is warranted.

The purpose of this study was to investigate the effects of daily exercise on susceptibility to sudden cardiac death. A 2 min coronary occlusion was initiated during the last minute of an exercise stress test and continued for 1 min after cessation of exercise in chronically instrumented dogs with a healed anterior wall myocardial infarction. Thirteen dogs developed ventricular fibrillation (VF; susceptible), while five did not (resistant). Before the exercise plus ischemia test, the baroreflex was evaluated with a bolus injection of phenylephrine (10 micrograms/kg). The changes in heart rate caused by a 30 mm Hg increase in systolic arterial pressure as well as the slopes of either heart rate or RR interval plotted against systolic arterial pressure were significantly lower in dogs that developed VR (resistant, -49.6 +/- 7.8; susceptible, -15.3 +/- 6.4 beats/min; p less than .001). Four resistant and eight susceptible animals were then placed on a 6 week daily exercise program, while eight susceptible dogs had an equal period of rest. At the end of the 6 week period the exercise plus ischemia test was repeated; no susceptible animal that performed daily exercise developed VF, and all but one of the rested animals did. Daily exercise improved baroreflex control of heart rate in the susceptible group but not in the resistant group. Rest did not alter baroreflex function (change in heart rate after 30 mm Hg increase in systolic arterial pressure: after 6 weeks of exercise, resistant -43.3 +/- 18.9 beats/min, susceptible -60.8 +/- 16.6 beats/min; after 6 weeks of rest, susceptible 27.4 +/- 11.0 beats/min). We conclude that daily exercise prevents VF induced by acute myocardial ischemia in a subpopulation of dogs that were previously identified as susceptible to sudden cardiac death. Exercise also altered the autonomic control of the heart, possibly decreasing sympathetic and/or increasing parasympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

The sections in this article are: 1 Hydrostatic Pressure 1.1 Models 1.2 Hydrostatic Indifference Point 1.3 Transmural Pressure and Tissue Filtration 2 Immediate Cardiovascular Responses to Posture Changes and Blood Volume Redistribution 2.1 Experimental Conditions 2.1.1 Lower-Body Negative Pressure 2.1.2 Passive Tilt 2.1.3 Immersion 2.1.4 G-Suit Devices 2.1.5 Lower-Body Positive Pressure 2.2 Blood Volume and Distribution 2.3 Intravascular and Intracardiac Pressures 2.4 Cardiac Dimensions and Pump Performance 2.5 Cardiac Output 2.6 Regional Flow 2.6.1 Brain 2.6.2 Myocardium 2.6.3 Skin and Muscle 2.6.4 Splanchnic Region 2.6.5 Kidneys 2.7 Postural Effects on Hemodynamic Responses to Exercise 2.8 Dynamic Responses to Posture Changes 2.8.1 Regulatory Mechanisms 2.8.2 Systemic Responses 3 Cardiovascular Adaptation to Prolonged Bed Rest, Zero Gravity, and Related Conditions 3.1 Experimental Conditions 3.1.1 Bed Rest 3.1.2 Head-Down Tilt 3.1.3 Immersion 3.1.4 Zero Gravity 3.2 Body Composition 3.3 Blood Volume 3.4 Cardiovascular Function 3.4.1 Maximal Oxygen Uptake 3.4.2 Cardiac Dimensions and Performance 3.4.3 Systemic Hemodynamics 3.4.4 Orthostatic Intolerance 3.5 Dynamic Responses 4 Hypergravic Conditions 4.1 Experimental Conditions 4.2 Fluid Shifts 4.3 Cardiac Dimensions and Performance 4.4 Cardiac Output and Regional Flow 4.4.1 Pulmonary Blood Flow 4.4.2 Brain 4.4.3 Splanchnic and Muscle Blood Flow 4.5 Dynamic Responses and Reflex Adjustments

The potential of left stellectomy in reducing the incidence of ventricular fibrillation associated with acute myocardial ischemia was investigated in a new animal model for sudden death. Thirty-two dogs had an anterior myocardial infarction produced by ligation of the left descending coronary artery. One week later they were randomly allocated to a control or to an experimental group that underwent left stellectomy. One month after ligation while the dogs were conscious, a balloon occluder previously positioned around the circumflex coronary artery was inflated and the ensuing coronary occlusion was maintained for 10 minutes. Ventricular fibrillation occurred in 11 of 17 (65%) control dogs, compared with five of 15 (33%) (p < 0.05) in the experimental group. Among the survivors the incidence of arrhythmias was less in the experimental group compared with the control group. Infarct size (21 +/- 2% vs 20 +/- 2%), resting heart rate (143 beats/min vs 127 beats/min) and QTc (347 +/- 11 msec vs 349 +/- 13 msec) were similar between control and experimental groups. The dogs that died had a greater increase in heart rate at 1 minute postocclusion than survivors and also had significantly longer QT intervals. Our study indicates that left stellectomy exerts a major protective effect in reducing the incidence of ventricular fibrillation when conscious dogs with a previous anterior myocardial infarction undergo acute myocardial ischemia. This simple and safe surgical procedure may be considered for a clinical trial in subgroups of patients with ischemic heart disease at very high risk for sudden death.