The effects of short-term environment-induced heat stress on the myocardium in male mice

Environment-induced heat stress (EIHS) is caused by a sustained elevation in body temperature due to prolonged exposure to excess heat and humidity. Given the current and increasing frequency of EIHS and the large gap in knowledge regarding EIHS-mediated impacts to the myocardium, the purpose of this investigation was to determine the extent EIHS alters cardiac health. We hypothesized EIHS would cause myocardial injury and cellular dysfunction. To test this hypothesis, 13 w old male C57 mice were exposed to EIHS for 4 h or 8 h (n=7; 37.7 ± 0.10 °C, 38.3 ± 0.5 % humidity) or thermoneutral (TN) (n=7, 27.7 ± 0.15 °C, 42.5 ± 0.43% humidity) conditions, hearts were removed, weighed, and portions of the heart were fixed for histology or frozen for biochemical measures. Environment-induced HS increased subcutaneous temperature following 4 and 8 h by 0.9 °C (p< 0.01) compared to respective TN temperatures and decreased body weight by 6.8% (p=0.01) at 4 h and 13% (p<0.01) at 8 h compared to TN. Histological inspection revealed that EIHS increased anisokaryosis by 1.4-fold following 4 h (p<0.01) and by 75% following 8 h (p=0.01) compared to TN animals. Environment-induced HS increased relative abundance of malondialdehyde-modified proteins (35%, p=0.02), a marker of oxidative stress, and increased relative protein abundance of SOD2 (72%, p=0.05) following 4 h compared to TN. Eight hours of EIHS increased relative protein abundance of SOD1 (69%, p=0.01) compared to TN and increased catalase and GPX1 compared to TN (91%, p<0.01; 2-fold, p<0.01) and compared to 4 h of EIHS (72%, p=0.03; 34%, p=0.01), though MDA-modified proteins were similar to TN. Following 4 h of EIHS, markers of mitochondrial abundance, including electron transport chain complexes II (69%, p=0.02) and V (36%, p=0.03), VDAC2 (79%, p=0.01) and PHB1 (65%, p=0.03) were increased compared to TN, and PDH (35%, p=0.04) and Cox IV (55%, p=0.01) were increased compared to 8 hrs of EIHS. Environment-induced HS appeared to alter mitochondrial fusion and fission as DRP1 (51%, p=0.05), phosphorylated (p)-DRP1 (47%, p=0.04), FIS1 (57%, p=0.01) and Mfn1 (26%, p=0.03) were increased compared to TN following 4 h and Mfn2 was increased (37%, p=0.02) following 8 h of EIHS compared to TN. Mitophagy markers BNIP3L/NIX and Pink1 were increased by EIHS following 4 h compared to TN (78%, p=0.02; 41%, p=0.03). Environment-induced HS increased autophagy markers ULK1 (36%, p<0.01), PI3K (80%, p<0.01), and ATG7 (49%, p<0.01) following 4 h compared to TN and ULK1 (33%, p<0.01) and ATG7 (41%, p=0.02) following 4 h compared to 8 h of EIHS. However, p-ULK1, Beclin, p-Beclin, ATG12, and ATG16 were similar between groups. Relative protein abundance of p62 and LC3 II were similar between groups; however, using a colchicine-inhibition approach, 8 h of EIHS caused a significant accumulation of p62, suggestive of increased flux. These data suggest that in a murine model of EIHS, 4 h was suffcient to cause cellular injury and dysfunction in the myocardium; however, as EIHS continued, it was associated with changes reflective of a cellular stress response that may contribute to acclimation. This work was supported by USDA 2020-02716. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.