It has been found that pretreatment with
ATP-dependent
potassium channel (
KATP-channel) opener,
BMS 180448 (3 mg/kg, intravenously), increases cardiac resistance against arrhythmogenic action of coronary artery occlusion and reperfusion in anaesthetized rats. However,
BMS 180448 induced a decrease in
ventricular fibrillation threshold in rats postinfarction cardiac
fibrosis. This effect was completely abolished by administration of the
KATP-channel inhibitor,
glibenclamide. By contrast, coadministration of
BMS 180448 and selective sarcolemmal
KATP-channel inhibitor,
HMR 1098, promoted an increase in
ventricular fibrillation threshold in rats with postinfarction cardiac
fibrosis before normal value. The selective mitochondrial
KATP-channel opener,
diazoxide, also exacerbated a decrease in
ventricular fibrillation threshold induced by postinfarction cardiac
sclerosis. But after depletion of endogenous
catecholamine storage by pretreatment with guanthidine,
diazoxide, on the contrary, elevated the
ventricular fibrillation threshold. It has been suggested that stimulation of mitochondrial
ATP-sensitive potassium channels promotes an elevation in electrical stability of the heart, whereas opening of sarcolemmal
KATP-channel increases a possibility of ventricular arrhythmias.