Long-term exposure to moderate cold reduces incidence of reperfusion tachyarrhythmias in rats.

Recently, moderate cold acclimation (9 °C; MCA) was found to exert cardioprotective effects by increasing resistance to ischemia-reperfusion (IR) injury and mitochondrial calcium overload in rats, but the effect of MCA on the incidence of IR arrhythmias is not known. The aim of this study was to determine whether MCA can induce an anti-arrhythmic effect and, if so, to elucidate a possible mechanism. Adult male Wistar rats were acclimated (9 °C) for short (1-3-10 days) and long-term (5 weeks; CA) periods, followed by a two-week recovery period (24 °C; CAR). The number of premature ventricular complexes (PVCs) and their duration after IR, western blotting, thin layer and gas chromatography were performed on left ventricular myocardium. We revealed that total reperfusion PVCs and tachyarrhythmia duration decreased even after CA, and accordingly the anti-arrhythmic n-3PUFAs increased in cardiac membrane phospholipids, the n-6/n-3 PUFA ratio decreased. CA increased the distribution of connexin 43 (Cx43) in favor of end-to-end junctions and the expression of uncoupling protein UCP3 in mitochondria. These beneficial effects were lost after two-weeks recovery period CAR. Interestingly, the mitochondrial antioxidants superoxide dismutase (SOD2) and thioredoxin reductase (TRXRD2) were strongly upregulated exclusively after 1 day of cold exposure, whereas cytosolic TRXRD1 was downregulated. In conclusion, long-term MCA (5-weeks) reduces the incidence of reperfusion arrhythmias, increases the proportion of anti-arrhythmic n-3PUFAs in cardiomyocyte membranes and has a positive effect on Cx43 distribution. By increasing the amount of UCP3 in mitochondria, it may reduce the likelihood of free radical formation in mitochondria during reperfusion.