Reperfusion arrhythmias in the murine heart: their characteristics and alteration after ischemic preconditioning.

Abstract

In this study, we examined the features of reperfusion arrhythmias and the effect of preconditioning (PC) in the mouse for future application of genetically engineered mice to study mechanisms of this type of arrhythmia. Under pentobarbital anesthesia, reperfusion arrhythmias were induced by temporary occlusion of the left anterior descending coronary artery and reperfusion in BALB/c AJc1 mice. In the first protocol, the coronary artery was occluded for periods ranging from 2 to 15 min and then reperfused. In the second protocol, hearts were preconditioned with 2- or 3-min ischemia and 5-min reperfusion prior to the 5 min of coronary occlusion. An electrocardiogram was recorded throughout the experiment, and arrhythmias were diagnosed according to the Lambeth Convention criteria. The incidences of reperfusion-induced ventricular tachycardia (VT) in hearts that received 2, 3, 5, 10 and 15-min ischemia (n = 10 approximately 14) were 0, 9, 73, 55 and 30 %, respectively. Ventricular fibrillation (VF) was not observed upon reperfusion regardless of the ischemia duration. PC with 2-min ischemia and with 3-min ischemia (n = 10 for each PC) reduced the incidences of reperfusion VT after 5-min ischemia to 40% and 10%, respectively. However, in mice that developed reperfusion VT, the VT duration was similar to that in non-preconditioned controls, ranging from 1 to 16 s. These results suggest that the relationship between ischemia duration and incidence of VT upon subsequent reperfusion is "bell shaped" and that PC has anti-arrhythmic effects in the mouse, as it does in anesthetized rat hearts. However, there appear to be differences in the incidence of reperfusion-induced VF and the duration of reperfusion VT between these species. Thus, the present murine preparation appears to be a useful model for studying the mechanism of reperfusion VT and PC, though it does not share all of the features of reperfusion arrhythmias with the anesthetized rat preparation.