Exertional heat stroke reduces acute circumferential cardiac strain in female mice

Introduction: Exposure to severe heat illness, particularly through exertional heat stroke (EHS), increases the risk of developing chronic cardiovascular disease (CVD), alters cardiac metabolomics, and may cause premature mortality. While EHS is the cause of thousands of emergency room visits per year in the US, it is not currently considered a risk factor for CVD later in life. Similarly, the pathophysiology of heat stress on the heart is poorly understood. Objective: The purpose of this study is to determine the long-term effects of EHS exposure on cardiovascular function. Methods: Sixteen female C57BL/6 mice (aged 12 weeks) underwent laparotomy for placement of core temperature telemetry transmitters. After recovery, the mice had access to a voluntary running wheel for three weeks before completing four incremental training sessions on a forced running wheel. Following a 48-hour rest period, they underwent either EHS – incremental exercise at elevated environmental temperatures (37.5°C) until exhibiting evidence of neurologic dysfunction (a hallmark of EHS) – or a sham exercise protocol (EXC). Four mice per treatment were monitored longitudinally over 18 weeks. Body mass, blood pressure, left ventricular wall distortion, functional echocardiography, and myocardial and endocardial circumferential cardiac strain were analyzed at baseline, two weeks, and then every four weeks post-treatment. Significance within and between treatments was determined using repeated measures 2-way ANOVA, followed by Tukey’s post hoc analysis. ( α=< 0.05). Results: Two weeks post-treatment, EHS females presented with significantly reduced myocardial and endocardial circumferential strain; however, these values recovered by 6 weeks. Both groups exhibited a significant increase in body weight, though EHS females gained weight significantly faster than EXCs. Both groups saw slight increases in mean arterial, systolic, and diastolic blood pressure at 2 weeks before significant declines beginning at 10 weeks. Systolic blood pressure significantly declined earlier in EHS females (10 weeks) compared to EXC controls (18 weeks). Chronically, EHS females had thinner left ventricular anterior walls during diastole when compared to the controls at both 6 and 14 weeks; no other differences in wall distortion were observed. Conclusions: A single bout of EHS significantly reduces acute circumferential strain and leads to rapid body mass gain. While many observed functional measures do recover, there are signs of acute stress-induced cardiac dysfunction and an increased predisposition for obesity. Supported by the US Army Medical Research and Developmental Command W81XWH-19-2-0050. RWK supported by the APS Summer Undergraduate Research Fellowship program. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.