The comparative effects of the
calcium-antagonists
gallopamil and
nifedipine on
ischemia-induced and reperfusion-induced ventricular arrhythmias, particularly
ventricular fibrillation (VF), were assessed in a total of 40 mongrel dogs in two experimental preparations. In part I of the study, changes in the time course of spontaneous ventricular arrhythmias and VF parallel to changes in epicardial conduction following acute coronary artery occlusion lasting 20 minutes and followed by subsequent reperfusion were determined. In part II, repeated coronary artery occlusions (20 min) followed by reperfusion (60 min) were performed, and changes in
ventricular fibrillation threshold (VFT) were assessed.
Gallopamil proved to be highly effective in preventing ventricular arrhythmias and VF following coronary delay was reduced. The
ischemia-induced fall in conduction delay was reduced. The
ischemia-induced fall in VFT occurring during the first few minutes after occlusion (phase Ia) was significantly reduced. In contrast,
nifedipine failed to influence the incidence of ventricular arrhythmias and VF. Following reperfusion, neither
drug reduced the incidence of VF nor the associated fall in VFT at the onset of reperfusion. The time course of recovery of epicardial conduction was not affected by either
drug. However, the increase in the VFT during the early postreperfusion period was significantly enhanced by both agents. The effects of
gallopamil were more pronounced than those of
nifedipine. Delayed reperfusion ventricular arrhythmias arising 5 to 10 minutes after release of coronary artery obstruction were significantly reduced by
gallopamil whereas
nifedipine proved ineffective. The results show that
calcium antagonists display direct antiarrhythmic and cardioprotective actions in acute transient
myocardial ischemia. The different effectiveness of
gallopamil compared to
nifedipine can be explained by differences in electrophysiological properties of the drugs. Enhanced ventricular vulnerability following acute transient coronary artery occlusion and subsequent release of coronary artery obstruction, first described by Tennant and Wiggers, has been extensively investigated over the past decade in a variety of experimental and clinical settings. However, the basic mechanisms underlying
ischemia- and reperfusion-induced ventricular arrhythmias and
ventricular fibrillation (VF) have not yet been fully elucidated. Furthermore, the results of pharmacological approaches to prevent ventricular arrhythmic activity are conflicting. The present study aimed to evaluate the antiarrhythmic efficacy of
calcium antagonists in acute
myocardial ischemia and reperfusion. We have examined the effects of
gallopamil and
nifedipine on the time course of ventricular arrhythmias during the first 20 minutes after acute coronary artery occlusion and subsequent reperfusion. We have studied the underlying mechanisms by mapping epicardial conduction and by assessing the electrically induced
ventricular fibrillation threshold (VFT) both within and outside ischemic areas.