Heat stress‐induced changes in the myocardium

Prolonged exposure to heat can lead to environment-induced heat stress (EIHS), which may be a threat to human health. How EIHS affects cardiac morphology and the myocardium are unknown. We hypothesized that EIHS would alter cardiac morphology and cause cellular dysfunction. To test this hypothesis, crossbred female pigs were exposed to thermoneutral (TN; 20.6 ± 0.2 ºC; n=8) or EIHS (37.4 ± 0.2 ºC; n=8) conditions for 24 h. Rectal temperature (RT), skin temperature (ST), and respiratory rate (RR) were recorded every 4 h during the environmental challenge. Pigs were euthanized following the environmental challenge and hearts were collected. Hearts were weighed and heart length (apex to base), width (left/right dimension), and left ventricle (LV) and right ventricle (RV) wall thickness were measured with calipers. Portions of LV and RV were lyophilized to measure tissue water content or homogenized for protein extraction and western blotting. Environment-induced heat stress increased RT by 1.3 ºC (p<0.01), ST by 11 °C (p<0.01) and RR by 72 breaths per minute (p<0.01) compared to TN. Heart weight tended to be decreased (7.6%; p=0.07) and heart length was decreased (8.5%; p=0.01) by EIHS, but heart width was similar between groups. Left ventricle wall thickness was increased (22%; p=0.02) and RV thickness was decreased (26%; p=0.04) in EIHS compared to TN. Water content in the RV was similar between groups, however, in LV it was increased (8.6%; p<0.01) in EIHS compared to TN, suggesting edema contributed to increased LV thickness. Lastly, using a western blot approach we discovered that pathways regulating energy homeostasis were impacted by EIHS and sometimes differed between RV and LV. In RV and LV, phosphorylation (p) of AMP-activated protein kinase (AMPK) was decreased by EIHS (RV - 73%, p<0.02; LV - 54%, p=0.04), and in the RV was accompanied by increased protein phosphate type 2A (PP2A; 15.5%, p<0.01), which regulates pAMPK, and decreased p-Acetyl-CoA carboxylase (ACC; 40%, p<0.01), a client protein of pAMPK, whereas these were similar in LV. In RV, mTOR signaling appeared to be blunted, mitochondrial content increased, and markers of mitophagy increased by EIHS compared to TN, however, LV was resistant to these changes. In total, these data demonstrate that a single bout of EIHS caused cardiac morphological changes and biochemical changes in the myocardium and that EIHS affects the LV and RV differently.