Endurance training in rats after small infarction, whether started early or late after left coronary artery ligation, was well tolerated without changes in LV volume, shape, hemodynamics, and long-term survival. Endurance training in rats with large infarction decreased overall survival (P < .0001). In survivors from late exercise, training caused aggravation of global LV dilation without additional shape changes. Endurance training after large infarction caused aggravation of remodeling to a degree that was not compatible with life in 27% of the rats with late exercise and in 48% with early exercise after coronary artery ligation, despite similar exercise. This was explained by extensive remodeling that was most pronounced in nonsurvivors from early exercise. In these rats, severe global LV dilation, distortion of LV shape, scar thinning, and a paradoxic reduction of septal thickness, ie, mismatch of infarcted and noninfarcted myocardia, were observed.

Connexin 43 is located in the cardiomyocyte sarcolemma and in the mitochondrial membrane. Sarcolemmal connexin 43 contributes to the spread of myocardial ischemia/reperfusion injury, whereas mitochondrial connexin 43 contributes to cardioprotection. We have now investigated the antiarrhythmic dipeptide ZP1609 (danegaptide), which is an analog of the connexin 43 targeting antiarrhythmic peptide rotigaptide (ZP123), in an established and clinically relevant experimental model of ischemia/reperfusion in pigs. Pigs were subjected to 60 min coronary occlusion and 3 h reperfusion. ZP1609 (n = 10) was given 10 min prior to reperfusion (75 μg/kg b.w. bolus i.v. + 57 μg/kg/min i.v. infusion for 3 h). Immediate full reperfusion (IFR, n = 9) served as control. Ischemic postconditioning (PoCo, n = 9; 1 min LAD reocclusion after 1 min reperfusion; four repetitions) was used as a positive control of cardioprotection. Infarct size (TTC) was determined as the end point of cardioprotection. Systemic hemodynamics and regional myocardial blood flow during ischemia were not different between groups. PoCo and ZP1609 reduced infarct size vs. IFR (IFR, 46 ± 4 % of area at risk; mean ± SEM; PoCo, 31 ± 4 %; ZP1609, 25 ± 5 %; both p < 0.05 vs. IFR; ANOVA). There were only few arrhythmias during reperfusion such that no antiarrhythmic action of ZP1609 was observed. ZP1609 when given before reperfusion reduces infarct size to a similar extent as ischemic postconditioning. Further studies are necessary to define the mechanism/action of ZP1609 on connexin 43 in cardiomyocytes.

Microembolization at reperfusion augments infarct size, but postconditioning in the presence of microembolization still reduces infarct size and attenuates infarct expansion.

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