Preconditioning in the absence or presence of sustained ischemia modulatesmyocardial Cx43 protein levels and gap junction distribution

In the heart, brief repeated episodes of ischemia prior to a sustained occl usion (ischemic preconditioning; PC) significantly delay the onset of necro sis and arrhythmogenesis. Ischemia has been reported to influence gap junct ion organization and connexin43 (Cx43) content, but whether PC affects thes e structures is not known. We investigated the effect of PC (2 cycles of 5- min ischemia plus 10-min reperfusion) followed by prolonged reperfusion wit hout concomitant regional coronary occlusion on the myocardial Cx43 content and its spatial distribution in rabbit hearts. We also compared the effect of sustained ischemia with or without PC on Cx43 spatial distribution. In experiments with PC only, there was an initial decrease in Cx43 levels with in the ischemic zone followed by a progressive increase after 48 h reperfus ion. End-to-end immunolabeling of Cx43 was augmented in the ischemic region between 24 and 48 h reperfusion; labeling was not uniquely confined to myo cyte abutments, but was also dispersed along the sarcolemma. Cx43 immunolab elling was more intense and diffuse in hearts subjected to PC before sustai ned coronary occlusion (compared to non-PC). These data indicate that gap j unctions are significantly altered during brief episodes of ischemia. Reorg anization of the gap junction complex could contribute to PC-mediated reduc tions in cardiac arrhythmias.