IN-VITRO EFFECTS OF CAPSAICIN - ANTIARRHYTHMIC AND ANTIISCHEMIC ACTIVITY

The antiarrhythmic effects of vehicle (0.1% dimethyl sulfoxide: DMSO) or capsaicin were evaluated in isolated perfused rat and guinea pig he art preparations. In the rat, capsaicin reduced ischemic ventricular t achycardia from 100% in control to 0%, and ischemic ventricular fibril lation from 60% in control to 0% at 30 mu M, and diltiazem reduced the incidence of ischemic ventricular tachycardia and ventricular fibrill ation to 55% and 0%, respectively. Reperfusion ventricular fibrillatio n was reduced from 90% to 20% and 33% for capsaicin and diltiazem, res pectively, at these concentrations. In isolated perfused globally isch emic rat hearts, antiischemic efficacy was assessed as a significant e xtension (36% and 50%) in time to contracture with 30 mu M capsaicin a nd 1 mu M diltiazem, respectively. Capsaicin reduced left ventricular developed pressure by 35% in non-ischemic rat hearts, and increased co ronary flow by 40%. The increased time to contracture for either compo und was not blocked by glyburide (0.1 mu M) suggesting a lack of any i nvolvement of ATP-sensitive K+ channels. In isolated guinea pig hearts subjected to global ischemia, capsaicin and diltiazem reduced reperfu sion ventricular fibrillation from 100% to 10% and 0% at 30 and 3 mu M , respectively. Electrophysiologic evaluation in guinea pig papillary muscles using standard microelectrode techniques demonstrated signific ant (P < 0.05) action potential durations at 90% repolarization shorte ning at 1 Hz by 9%, 28% and 39%, and 23%, 37% and 51% at 10, 30, and 1 00 mu M of capsaicin or diltiazem, respectively. Unlike diltiazem, no changes in action potential duration were observed with capsaicin (up to 100 mu M) at faster stimulation rates (5 Hz). In conclusion, capsai cin displays both antiarrhythmic and antiischemic efficacy. These data suggest that the effects of capsaicin are mediated primarily through block of Ca2+ channels in these preparations.