Effect of a 'vagomimetic' atropine dose on canine cardiac vagal tone and susceptibility to sudden cardiac death

We manipulated the level of cardiac vagal tone in dogs with healed myocardial infarctions during exercise plus acute ischemia, to explore vagal involvement in the pathophysiology of sudden cardiac death.We occluded the circumflex coronary artery during the last minute of treadmill exercise in 32 dogs with healed anterior myocardial infarctions. Twenty-one dogs experienced ventricular fibrillation (susceptible) and 11 did not (resistant). On a subsequent day, we gave intravenous low dose atropine to susceptible dogs to increase their levels of cardiac vagal tone, as estimated by moving polynomial time-series analysis of R-R interval variability (0.24-1.04 Hz).We also measured vagal responses to coronary occlusion at rest, before and after low-dose atropine. In susceptible dogs, atropine increased the average vagal tone index at rest (atropine: 7.3 +/- 0.4 versus control: 6.6 +/- 0.5 In ms(2), P < 0.01) and during maximum exercise (atropine: 2.5 +/- 0.4 versus control: 1.6 +/- 0.3 ln ms(2) P < 0.01), but failed to prevent ventricular fibrillation induced by exercise plus ischemia. Time to ventricular fibrillation actually decreased from 63 +/- 3 to 42 +/- 2s (P < 0.01), and R-R interval shortening elicited by coronary occlusion increased (atropine: Delta -144 +/- 64 versus. control: Delta -55 +/- 32 ms, P < 0.01). In resting susceptible dogs, atropine significantly increased preocclusion indexes of vagal tone (atropine: 7.8 +/- 0.3 versus control: 6.9 +/- 0.4 ln ms(2), P < 0.01), but did not prevent large reductions of vagal tone during ischemia (atropine: Delta -4.4 +/- 0.6 versus control: Delta -3.8 +/- 0.4 ln ms(2) P > 0.05).We conclude that increases of resting vagal tone after low-dose atropine in dogs with healed anterior myocardial infarctions do not protect against sudden cardiac death. Quite the contrary, vagal tone is withdrawn more completely during ischemia, and the time to ventricular fibrillation during exercise plus ischemia is shortened. Clin Auton Res 8:155-164 (C) 1998 Lippincott-Raven Publishers.