Effects of the blockade of cardiac sarcolemmal ATP-sensitive potassium channels on arrhythmias and coronary flow in ischemia-reperfusion model in isolated rat hearts

Gok S.; Vural K.; Sekuri C.; Onur R.; Tezcan A.; Izanli A.

Effects of the blockade of cardiac sarcolemmal ATP-sensitive potassium channels on arrhythmias and coronary flow in ischemia-reperfusion model in isolated rat hearts

Date

2006

Authors

Abstract

Activation of ATP-sensitive K+ channels (KATP) during ischemia leads to arrhythmias and blockade of these channels exert antiarrhythmic action. In this study, we investigated the effects of HMR1098, a sarcolemmal KATP channel blocker and 5-hydroxydeconoate (5-HD), a mitochondrial KATP channel blocker on cardiac function and arrhythmias in isolated rat hearts. The hearts were subjected to 30 min coronary occlusion, followed by 30 min reperfusion. In the preischemic period, both HMR 1098 and 5-HD slightly increased coronary perfusion pressure. Coronary occlusion increased the perfusion pressure and decreased the left ventricular developed pressure (LVDP) in both control and drug-treated hearts. However, inhibition of LVDP was greater and recovery of the perfusion pressure was lower in 30 μmol/l HMR1098 and 100 μmol/l 5-HD-treated hearts compared to control (P < 0.05). HMR1098, at 3 μmol/l, but not at 30 μmol/l, significantly reduced the ratio of bigeminis, couplets and salvos (P < 0.05). Ventricular tachycardia and ventricular fibrillation were not prevented by HMR1098, at both concentrations, and with 5-HD (100 μmol/l). These results suggest that blockade of sarcKATP and mitoKATP channels exert weak antiarrhythmic action, but reduce the recovery of coronary perfusion and contractile force, implying that both types of KATP channels have beneficial role in the recovery of ischemic rat myocardium. © 2005 Elsevier Inc. All rights reserved.