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

Abstract

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 antiarrhythmic 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 wk; CA) periods, followed by a 2-wk recovery period (24°C; CAR). The number of premature ventricular complexes (PVCs) and their duration after IR were determined. Left ventricular myocardium was analysed by western blotting, TLC & GC chromatography and immunofluorescence microscopy. We revealed that total reperfusion PVCs and tachyarrhythmia duration decreased even after CA, and accordingly, the antiarrhythmic n-3 PUFAs 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 3 (UCP3) in mitochondria. These beneficial effects were lost after 2-wk 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-wk) reduces the incidence of reperfusion arrhythmias, increases the proportion of antiarrhythmic 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.NEW & NOTEWORTHY Moderate cold acclimation (CA) gradually reduces total reperfusion PVCs and tachyarrhythmia duration in rat myocardium, detectable after 5 wk and lost after a 2-wk recovery. Reduced n-6/n-3 PUFA ratio, protective Cx43 and UCP1 distribution, and increased GPX4 expression supports the antiarrhythmic effect elicited by CA. Mitochondrial antioxidants SOD2 and TXNRD2 are upregulated after just 1 day of exposure. The brown adipose tissue-to-body weight ratio increases during CA, and mitochondrial density exhibits an independent pattern of change.