Antiarrhythmic action of labetalol and its effect on adenine metabolism in the isolated rat heart

Abstract

Labetalol, a combined alpha- and beta-adrenergic antagonist, was assessed for antiarrhythmic activity in the isolated perfused rat heart. Inclusion of 5.0 and 7.5 mumol/liter labetalol in the perfusate reduced the fall in ventricular fibrillation threshold and eliminated ventricular arrhythmias during the coronary occlusion period of 15 minutes. In treated hearts, levels of high energy phosphates were significantly higher and lactate, adenosine and hypoxanthine levels were lower in ischemic myocardium. Cyclic adenosine monophosphate levels were reduced in uninvolved myocardium (0.31 +/- 0.01 and 0.24 +/- 0.02 versus 0.43 +/- 0.02 nmol/g fresh weight) and in the ischemic myocardium (0.38 +/- 0.02 and 0.34 +/- 0.04 versus 0.65 +/- 0.05 nmol/g) in hearts treated respectively with 5.0 and 7.5 mumol/liter labetalol versus control hearts. When untreated hearts were perfused with 3.0 mmol/liter potassium in perfusate, all had ventricular tachycardia or fibrillation during coronary ligation and developed ventricular fibrillation after reperfusion. Labetalol, 5.0 mumol/liter, reduced ventricular tachyarrhythmias during coronary occlusion and after reperfusion, whereas labetalol, 7.5 mumol/liter, eliminated tachyarrhythmias during occlusion and reperfusion. Labetalol had potent antiarrhythmic activity in the hearts rendered uniformly prone to arrhythmias by perfusion with a low potassium solution.