Heat Acclimation Training Attenuates Oxidative Stress and Improves Mitochondrial Function to Protect the Heart from Exertional Heat Stroke in Mice

Introduction: Exertional heat stroke (EHS) leads to cardiac structural damage and functional impairment. Heat acclimation training may serve as an effective strategy to prevent and mitigate such damage, yet the underlying molecular and cellular alterations remain unclear. Methods: A C57BL/6N mouse model was used to study EHS-induced myocardial injury and evaluate the cardioprotective effects and mechanisms of heat acclimation training. Cardiac injury was assessed via plasma biomarkers, echocardiography, and histopathology, and transcriptomic analysis revealed links among injury, oxidative stress, and mitochondrial alterations. Transmission electron microscopy, O2K respirometry, and redox measurements further elucidated the mechanisms underlying mitochondrial structural and functional changes. Results: EHS was associated with structural damage to myocardial tissue, including myocardial fibrosis, pathological echocardiographic changes and a substantial elevation of the myocardial injury biomarker (cardiac troponin I). Mitochondrial structural disruption, impaired respiratory capacity, decreased adenosine triphosphate production and disrupted redox balance were identified as potential contributors to these pathological changes. HA training was associated with attenuated EHS-induced myocardial damage, as evidenced by the amelioration of cardiac dysfunction and histopathological alterations, mitigation of mitochondrial structural damage, restoration of mitochondrial function and increase in antioxidant capacity. Furthermore, HA training enhanced the thermoregulatory capacity and aerobic endurance of mice under high-temperature conditions. Transcriptomic analysis revealed that biological processes and signalling pathways enriched in differentially expressed genes with mitochondrial dysfunction and oxidative stress. Conclusion: This work identifies transcriptional alterations and signaling pathways associated with EHS-induced myocardial injury, suggesting pivotal roles for mitochondrial dysfunction and oxidative stress. Additionally, this research provides a theoretical basis and potential intervention targets for the prevention and mitigation of heat stress-induced cardiovascular damage through HA training.