INFLUENCE OF INDAPAMIDE AND CHLORTHALIDONE ON REPERFUSION-INDUCED VENTRICULAR-FIBRILLATION IN ISOLATED GUINEA-PIG HEARTS

The delayed rectifier potassium current (I-K) is a major repolarizing current in guinea pig ventricular myocytes. Blockade of I-K or other r epolarizing currents is of increasing interest for development of anti arrhythmic drugs; however, these interventions may also be proarrhythm ic. In the present study, we compared the potential antiarrhythmic pro perties of indapamide and chlorthalidone, two structurally related sul fonamide diuretics which differ in their ability to block the slow com ponent of the delayed rectifier (I-Ks) in isolated, buffer-perfused gu inea pig hearts. Hearts underwent 30-min global no-now ischemia and 10 -min reperfusion. Dose-response (10(-7)-10(-4)M) effects of indapamide or chlorthalidone on reperfusion-induced arrhythmias, coronary flow, and heart rate (HR) were evaluated in a randomized blinded fashion. Th ere was no significant difference in the incidence of ventricular fibr illation (VF) for either compound as compared with untreated controls. However, VF duration was reduced to <40 s in all hearts treated with indapamide 10(-4)M. Mean VF duration with indapamide 10(-4)M was 31 +/ - 4 versus 70 +/- 40 s in controls (p < 0.05). Chlorthalidone did not protect against reperfusion-induced arrhythmias. HR was unchanged with either compound; coronary flow during the control perfusion period in creased approximate to 43% with indapamide 10(-4)M (p < 0.05 vs, all t reatment groups). These results demonstrate that indapamide, but not c hlorthalidone, confers significant protection against reperfusion-indu ced VF in this experimental preparation and suggest that selective blo ck of I-Ks may be antiarrhythmic.