MODULATION OF QUINIDINE-INDUCED ARRHYTHMIAS BY TEMPERATURE IN PERFUSED RABBIT HEART

We used low temperature to slow ion channel kinetics and studied the e lectrophysiological effects of quinidine at different pacing rates in isolated rabbit hearts. Fifteen epicardial electrograms together with an endocardial monophasic action potential were recorded. Epicardial a ctivation and local recovery times were measured. Arrhythmias together with the characteristics of their mode of induction and rate were ana lyzed by epicardial activation sequence mapping. In the presence of qu inidine, arrhythmias consistent with both triggered activity and reent ry were observed. At baseline, triggered activity was not inducible, e ven though at 25 degrees C the recovery time was greater than that in the presence of quinidine at 36 degrees C. Also, with quinidine, the i ncidence of triggered activity decreased at 30 and 25 degrees C. There fore prolongation of the recovery time per se does not cause triggered activity. Quinidine's use-dependent effects on conduction and reverse use-dependent effects on recovery time were amplified by low temperat ures. These findings can be understood in terms of the known temperatu re sensitivities of the kinetics of the membrane ion channels responsi ble for activation and recovery. The results demonstrate that temperat ure can be used as a tool to elucidate mechanisms of drug action.