Chronic Heat Preconditioning Enhances Skeletal Muscle Function during Hypoxia and Reoxygenation

Skeletal muscle that is exposed to hypoxia followed by reoxygenation (H/R) is susceptible to dysfunction and fatigue. However, the mechanisms that underlie skeletal muscle fatigue during H/R are not completely understood. The purpose of our study was to determine the role that chronic heat preconditioning (CHP) may play in protecting skeletal muscle against the deleterious effects of H/R. We hypothesized that CHP would mitigate skeletal muscle fatigue and attenuate ROS formation during H/R. During CHP treatment, C57BL/6 mice were housed in a heating chamber at 42°C for 30 minutes. Next, the mice were transferred to another chamber at room temperature for 30 minutes. This cycle was repeated 3 times per day, 5 days/week, for 2 weeks. Following CHP, mice were sacrificed and their diaphragms were removed for muscle function analysis. The muscle strips were electrically stimulated in a contraction chamber filled with Ringer's solution during H/R. Our data revealed that CHP significantly increased muscle function during hypoxia (31.5 ± 1.7% for treated vs. 13.1 ± 2.7% for control, p < 0.05; expressed as percent of the maximal force at the end of the contraction protocol) and also showed a trend to increase muscle fatigue resistance during reoxygenation. We monitored cellular levels of reactive oxygen species (ROS) via confocal microscopy by utilizing dihydrofluorescein diacetate (Hfluor‐DA), which is a fluorescent probe sensitive to intracellular ROS. Compared to the non‐treated group, CHP‐treated muscle strips demonstrated mitigated ROS fluorescence at the end of both hypoxia and reoxygenation periods, respectively ( p < 0.05). Our results suggest that CHP may play a protective role against muscle fatigue and ROS formation during H/R in skeletal muscle. Support or Funding Information Supported by OU General Fund G110