[Prevention of ischemic and reperfusion arrhythmias using the calmodulin blocker trifluoperazine]

Models of ischemic and reperfusion arrhythmias were reproduced in isolated rat hearts by means of the ligation and subsequent reocclusion of the left descending coronary artery. The introduction of trifluoperazine (TFP, 10(-6) M) and verapamil (2.5 X 10(-8) M) into the perfusion medium produced a 20% depression of contractility in aerobic conditions; an additional depression of contractility at 20 min of ischemia and 10 min of reperfusion was 40 and 50%, respectively, for TFP and about the same for verapamil, as compared to the control. Antiarrhythmic effect of TFP was much higher, as compared to that of verapamil. The calmodulin blocker reduced fivefold total duration of arrhythmias, whereas the calcium-incorporation blocker only reduced it by 2.5 times. The antiarrhythmic effect of TFP was even more marked, as compared to verapamil, at reperfusion: TFP reduced total duration of ventricular tachycardias and ventricular fibrillations by 2 and 35 times, respectively, while verapamil had no effect on those types of arrhythmia. A possible mechanism of antiarrhythmic action of the calmodulin blocker TFP is discussed.