Electrophysiologic and Antiarrhythmic Effects of Phentolamine in Experimental Coronary Artery Occlusion and Reperfusion in the Dog

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Abstract
We studied the electrophysiologic and antiarrhythmic effects of phentolamine on ventricular arrhythmias seen after acute coronary artery occlusion and reperfusion in the anesthetized dog. One group of animals underwent proximal left circumflex artery occlusion for 1 hr followed by 4 hr of reperfusion. One-half received phentolamine, 0.25 mg/kg bolus, 30 min before occlusion, followed by continuous intravenous infusion of 0.15 mg/kg/min throughout the experiment, while the other half received saline and served as controls. Phentolamine reduced the number of premature ventricular contractions (PVCs) during the reperfusion period but had no effect on postocclusion arrhythmias. Another group of dogs underwent ligation of two consecutive left anterior descending diagonal branches for 1 hr followed by reperfusion. Effective refractory periods and ventricular activation times were measured before occlusion, every 10 min during occlusion, and every 10 min during reperfusion in both normal and ischemic zones. In this model, phentolamine reduced both the number of PVCs and the complexity of ventricular ectopy seen in the first 10 min after reperfusion. Compared to control, phentolamine decreased the shortening of ischemic zone refractory period seen after occlusion and prevented the overshoot seen after reperfusion. Phentolamine had no effect on ventricular activation times or mean blood pressure. Phentolamine is effective in preventing reperfusion ventricular arrhythmias and may act by decreasing the dispersion of refractoriness between normal and ischemic zones during coronary occlusion and reperfusion and by preventing the rapid increase in refractory period after reperfusion.

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