Local conduction during acute myocardial infarction in rats: Interplay between central sympathetic activation and endothelin

Abstract

We investigated the effects of autonomic dysfunction and endothelin on local conduction and arrhythmogenesis during myocardial infarction. We recorded ventricular tachyarrhythmias, monophasic action potentials, and activation sequences in wild-type and ETB-deficient rats displaying high endothelin levels. Central sympathetic inputs were examined after clonidine administration. Clonidine mitigated early and delayed arrhythmogenesis in ETB-deficient and wild-type rats, respectively. The right ventricular activation delay increased in clonidine-treated ETB-deficient rats and slightly decreased in wild-type rats. The left ventricular voltage rise decreased in all groups, whereas the activation delay increased mainly in clonidine-treated ETB-deficient rats. Central sympathetic activation and endothelin modulate ischemia-induced arrhythmogenesis. Ischemia alters excitability, whereas endothelin impairs local conduction, an action partly counterbalanced by central sympathetic activity.

Endothelin System and Ischemia-Induced Ventricular Tachyarrhythmias

“…The latter mechanism has been demonstrated in cellular electrophysiologic studies, but its importance during acute myocardial ischemia is unclear. Of note, preliminary in vivo experiments by our group lend support to these findings, after the analysis of local activation in the ventricular myocardium, by means of multi-electrode array recordings [ 20 ]. Based on the potential importance of this mechanism, further investigation is required on the effects of the endothelin system on electrical conduction in the ischemic myocardium.…”

Autonomic function and ventricular tachyarrhythmias during acute myocardial infarction

“…Thus, in addition to ionic imbalance, sympathetic activation enhances the dispersion of repolarization across the energy-depleted ischemic myocardium and lowers the fibrillation-threshold[11], perhaps without altering local conduction[12]. By contrast, parasympathetic stimulation prolongs the action potential duration and the effective refractory period[13]; hence, vagal activation exerts potent anti-fibrillatory actions on the ischemic myocardium, although transmural dispersion of repolarization seems unaffected[14].…”

“…The effects of the autonomic nervous system on ventricular electrophysiology during myocardial ischemia have attracted rigorous research efforts[ 11 - 14 ]: Sympathetic activation shortens the ventricular action potential and the refractory period under normal conditions, but these actions vary in the ischemic ventricular myocardium. Thus, in addition to ionic imbalance, sympathetic activation enhances the dispersion of repolarization across the energy-depleted ischemic myocardium and lowers the fibrillation-threshold[ 11 ], perhaps without altering local conduction[ 12 ]. By contrast, parasympathetic stimulation prolongs the action potential duration and the effective refractory period[ 13 ]; hence, vagal activation exerts potent anti-fibrillatory actions on the ischemic myocardium, although transmural dispersion of repolarization seems unaffected[ 14 ].…”