Heat Stress More Negatively Impacts Cardiac Muscle Mitochondria in Female Versus Male Pigs

With continued trends toward more frequent and more severe heat events there is a greater risk of environment-induced heat stress (HS). How persistently elevated core temperatures impacts body tissues remains largely unknown. Our preliminary evidence indicates HS may negatively impact cardiac tissue and that biological sex may play a role in HS-mediated pathology. To further test the hypothesis that cardiac muscle mitochondria are more negatively impacted by HS in females than in males, samples were isolated from the left ventricle (LV) of the heart from 3-month-old castrated male and prepubertal female pigs that were exposed to thermoneutral (TN) conditions (n = 4 per sex) or HS conditions for 24 h at 37°C (HS; n = 6 per sex). Samples were analyzed for citrate synthase (CS) and cytochrome c oxidase (COX) activities, and for mitochondrial oxidative phosphorylation (P) and electron transfer (E) capacities via high resolution respirometry. Data were analyzed by mixed linear models in SAS v9.4 with treatment, sex, and treatment × sex as fixed effects. A traditional marker of mitochondrial volume density, CS activity, tended to be greater in TN males compared to HS males (P = 0.08) but was unaffected by HS in female pigs. Conversely, intrinsic (relative to CS activity) mitochondrial function, as measured by COX activity, was greater in TN females than HS females (P = 0.04) and within HS, males maintained greater intrinsic mitochondrial function than females (P = 0.02). Both integrative (relative to tissue wet weight) and intrinsic mitochondrial leak respiration were greater in HS than TN pigs (P = 0.03) but the contribution of leak to total E (flux control ratio; FCRLEAK ) tended to be greater in males than females (P = 0.07). Conversely, both integrative and intrinsic maximal E (ECI+II ) tended to be greater in female than male pigs (P = 0.08) indicating a greater degree of excess electron transfer capacity in females. The contribution of complex I-supported P (PCI ) to total E (FCRPCI ) tended to be greater in TN compared to HS pigs regardless of sex (P = 0.09) and the contribution of maximal P to E (FCRPCI+II ) was greater in TN females compared to HS females (P = 0.05). This resulted in the FCRPCI+II being greater in males compared to females in the HS condition (P = 0.01), suggesting greater coupling of oxidative phosphorylation and electron transfer in cardiac mitochondria in males during 24 h of HS. These results suggest that HS may negatively impact cardiac muscle mitochondria in female pigs compared to males. Moreover, these data indicate that persistent HS has deleterious consequences for the myocardium and may represent an additional health concern caused by global climate trends. This project was supported by USDA NIFA Award #2020-68014-31954.