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(Circulation. 1995;91:2516-2519.)
© 1995 American Heart Association, Inc.

Articles

Do Increases in Markers of Vagal Activity Imply Protection From Sudden Death?

The Case of Scopolamine

Stephen S. Hull, Jr, PhD; Emilio Vanoli, MD; Philip B. Adamson, MD, MSc; Gaetano M. De Ferrari, MD; Robert D. Foreman, PhD; Peter J. Schwartz, MD

From the Department of Physiology (S.S.H., E.V., P.B.A., R.D.F., P.J.S.), College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Okla; Istituto di Clinica Medica Generale e Terapia Medica (G.M.D.), Universitá di Milano, Milano, Italy; Department of Internal Medicine (P.B.A.), University of Oklahoma Health Sciences Center, Cardiovascular Diseases Section, Oklahoma City, Okla; and Dipartimento di Medicina Interna (E.V., P.J.S.), Sezione di Cardiologia, Universitá di Pavia, IRCCS, Policlinico San Matteo, Pavia, Italy.

Correspondence to Stephen S. Hull, Jr, PhD, University of Oklahoma Health Sciences Center, College of Medicine, Department of Physiology, Biomedical Sciences Building, Rm 653, PO Box 26901, Oklahoma City, OK 73190. E-mail stephen-hull@uokhsc.edu.

Background Low-dose scopolamine increases heart rate variability (HRV) in patients with a prior myocardial infarction (MI). This observation, combined with the evidence that elevated cardiac vagal activity during acute myocardial ischemia is antifibrillatory, has generated the hypothesis that scopolamine might be protective after MI. We tested low-dose scopolamine in a clinically relevant experimental preparation for sudden death in which other vagomimetic interventions are effective.

Methods and Results Nineteen mongrel dogs that survived an anterior MI were used in the study. Occurrence or lack of ventricular fibrillation (VF) due to acute myocardial ischemia during submaximal exercise identified dogs at high and low risk for sudden death. Dose-response curves performed in 12 dogs at high (n=6) and low (n=6) risk showed that scopolamine at 3 µg/kg exerts the greatest effect on HRV. A second group of 7 high-risk dogs were exposed to an exercise-and-ischemia test after treatment with scopolamine (3 µg/kg IV). Scopolamine increased the standard deviation of RR intervals by 41%, increased the high-frequency band of spectral analysis by 48%, and decreased resting heart rate by 14%. Despite the increase in markers of vagal activity, VF recurred during the exercise-and-ischemia test in 6 dogs (86%).

Conclusions The significant increase in HRV induced by acute scopolamine did not result in a decreased risk for VF due to acute myocardial ischemia in association with sympathetic activation. Caution must be applied when extrapolating the potential antifibrillatory activity of an intervention from its influence on autonomic markers.

Key Words: scopolamine • death, sudden • ischemia • myocardial infarction

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