ANTIARRHYTHMIC AND METABOLIC EFFECTS OF INDORAMIN DURING ACUTE REGIONAL ISCHEMIA AND REPERFUSION IN ISOLATED RAT-HEART

The antiarrhythmic effect of α1-adrenbceptor antagonists during myocardial ischemia and reperfusion remains controversial. The potential antiarrhythmic properties of indoramin, an α1-antagonist, were assessed in the isolated perfused rat heart during regional ischemia and during sustained reperfusion. Coronary artery ligation (CAL) decreased the ventricular fibrillation threshold (VFT) of control hearts from 9.1 ± 1.3 (pre-CAL, mean ± SEM) to 2.1 ± 0.5 mA 15 min post-CAL (p < 0.0001). Perfusion with indoramin 10-8 M (α1-receptor antagonistic concentration) started 5 min prior to CAL did not prevent the fall in VFT after CAL. Indoramin 10-6 M prevented the fall in VFT after CAL relative to the control group. Indoramin 10-5 M markedly increased the VFT before CAL from 9.9 ± 1.0 to 28.6 ± 2.9 mA (p < 0.0001) and prevented the fall in VFT after CAL. During reperfusion, indoramin 10-5 M decreased the incidence of spontaneous ventricular fibrillation (VF) to 1 of 6 vs. 6 of 6 in the control group (p < 0.02). Indoramin 10-5 M preserved adenosine triphosphate in the reperfused myocardium: 2.82 ± 0.06 vs. 2.16 ± 0.21 μmol/g in the control group (p < 0.05). Specific α1-antagonist properties of indoramin did not appear to be involved in the antiarrhythmic effects. © 1990 Raven Press, Ltd., New York.