EFFECTS OF ATP-DEPENDENT K-REPERFUSION RABBIT ISOLATED HEART MODEL WITH PROGRAMMED ELECTRICAL-STIMULATION( CHANNEL MODULATORS ON AN ISCHEMIA)

The effects of glibenclamide and BRL-38227 were studied in isolated ra bbit hearts subjected to ischemia and programmed electrical stimulatio n. Coronary artery occlusion over 24 min decreased the ventricular eff ective refractory period in the ischemic zone. BRL-38227 (0.1 mu M) sh owed significant coronary vasodilator effects, but failed to modify th e ventricular effective refractory period under these conditions. A hi gher concentration (5 mu M) Of BRL-38227 potentiated the ischemia indu ced ventricular effective refractory period shortening effects. Gliben clamide (0.1 and 1 mu M) delayed the onset of the ischemia-induced ven tricular effective refractory period shortening. Glibenclamide (1 mu M ) inhibited the potentiated ventricular effective refractory period sh ortening effects of BRL-38227 (5 mu M) during ischemia, but failed to antagonise the coronary vasodilator effects of BRL-38227 (5 mu M). A h igher incidence of ventricular fibrillation was inducible when an extr a beat was applied in the ischemic zone through programmed electrical stimulation. The incidence of programmed electrical stimulation induce d ventricular fibrillation was increased by BRL-38227 (5 mu M) and ant agonised by glibenclamide (1 mu M). The results suggest that high conc entrations of K-ATP-activators can accentuate ischemia-induced decreas es in refractory period and increase the susceptibility of hearts to v entricular fibrillation when an extra beat is applied to the ischemic myocardium. These effects did not occur at lower coronary vasodilating concentrations of BRL-38227.