Effect of coronary perfusion of heptanol on conduction and ventricular arrhythmias in infarcted canine myocardium

Abstract

Introduction: Abnormal cellular coupling is a major constituent of the slow, dissociated conduction that supports ventricular tachycardia (VT) following myocardial infarction. Agents that modulate cellular coupling may exert either proarrhythmic or antiarrhythmic effects.

Methods and results: The effects of modulating cellular coupling on conduction and susceptibility to inducible VT were studied in 11 dogs with healed left anterior descending (LAD) infarction. The LAD circulation was isolated and supplied with arterial blood via a constant-flow bypass system. Localized intracoronary infusion of heptanol, an agent with relatively specific effects on intracellular coupling, was performed using this bypass system. Heptanol produced dose-dependent changes in cardiac conduction, assessed by delayed local activation times in sinus rhythm (0.5 mM: 11.9% +/- 11.0% change, P = 0.005; 1.0 mM: 45.8% +/- 25.5% change, P = 0.0004) and slowed conduction velocity both transverse and longitudinal to fiber orientation. Sustained VT was not induced in any of the control animals. During infusion of 0.5 mM heptanol, uniform sustained VT was inducible in 4 of 11 animals (P = 0.027). During infusion of 1.0 mM heptanol, sustained VT was induced in only 1 of 9 animals.

Conclusions: In the canine model of healed myocardial infarction, heptanol had a bimodal effect on susceptibility to inducible VT. Low-dose heptanol facilitated the induction of sustained VT, and high-dose heptanol had an antiarrhythmic effect. This suggests that agents that modulate coupling may significantly modify susceptibility to VT following myocardial infarction.