Pavel Vebr, Frantisek Galatik, Aneta Marvanova, Barbara Elsnicova, Daniela Hornikova, Marek Vecka, Sarka Spinová, Olga Novakova, Jitka M Zurmanova
{"title":"Long-term exposure to moderate cold reduces incidence of reperfusion tachyarrhythmias in rats.","authors":"Pavel Vebr, Frantisek Galatik, Aneta Marvanova, Barbara Elsnicova, Daniela Hornikova, Marek Vecka, Sarka Spinová, Olga Novakova, Jitka M Zurmanova","doi":"10.1152/japplphysiol.00509.2025","DOIUrl":null,"url":null,"abstract":"<p><p>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.<b>NEW & NOTEWORTHY</b> 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.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1156-1168"},"PeriodicalIF":3.3000,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of applied physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1152/japplphysiol.00509.2025","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/23 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
The Journal of Applied Physiology publishes the highest quality original research and reviews that examine novel adaptive and integrative physiological mechanisms in humans and animals that advance the field. The journal encourages the submission of manuscripts that examine the acute and adaptive responses of various organs, tissues, cells and/or molecular pathways to environmental, physiological and/or pathophysiological stressors. As an applied physiology journal, topics of interest are not limited to a particular organ system. The journal, therefore, considers a wide array of integrative and translational research topics examining the mechanisms involved in disease processes and mitigation strategies, as well as the promotion of health and well-being throughout the lifespan. Priority is given to manuscripts that provide mechanistic insight deemed to exert an impact on the field.