Hygrothermal stress increases malignant arrhythmias susceptibility by remodeling connexin43 via AMPK

Abstract

Abstract High mortality due to hygrothermal stress (high temperature and humidity, HHS) during heat waves is mostly linked to cardiovascular malfunction, the most serious of which are malignant arrhythmias. However, the mechanism associated with HHS leading to malignant arrhythmias remains unclear. Here, SD rats were exposed to 40°C and 85% humidity for constructing the HHS model, and the incidence of arrhythmic events, as well as the expression, phosphorylation, and distribution of Cx43 in the myocardium, were examined. The adenosine monophosphate-activated protein kinase (AMPK) activator, AICAR, was also administered to investigate the role played by AMPK in the process. Our results showed that HHS could induce malignant arrhythmias such as ventricular tachycardia (VT), ventricular fibrillation (VF), and severe atrioventricular block (AVB). Besides, HHS increased the distribution of "side-to-side" connections, decreased the phosphorylation of Cx43, and enhanced myocardial fibrosis. Furthermore, HHS also caused LKB1 and p-AMPK expression to be less abundant. While, pretreatment with AICAR could significantly ameliorate Cx43 remodeling and malignant arrhythmias, indicating that the HHS-induced arrhythmias is associated with the redistribution of gap junctions in cardiomyocytes, the dysfunction of intercellular conduction, and the organism's energy metabolism.