REDUCTION OF ISCHEMIC DAMAGE IN ISOLATED RAT HEARTS BY THE POTASSIUM CHANNEL OPENER, RP-52891

Potassium channel activators have been shown to protect ischemic myocardium. We studied the ability of the novel potassium channel activator, RP 52891, to also reduce ischemic damage in isolated globally ischemic rat hearts. RP 52891 (1-100 μM) was given before the hearts were subjected to 25 nun of ischemia and 30 min of reperfusion. Before ischemia, RP 52891 reduced contractile function only at the highest concentration (100 μM). Significant reductions in ischemie damage were observed at 3 μM and higher concentrations. RP 52891 improved reperfusion contractile function and reduced lactate dehydrogenase release. Contracture was significantly reduced by RP 52891 during reperfusion. The protective effects of RP 52891 were completely reversed by glyburide and sodium 5-hydroxyde-canoate, both Mockers of ATP-sensitive potassium channels. Thus, RP 52891 has direct cardioprotective efficacy, which may be related to activation of ATP-sensitive potassium channels. © 1990.