Hypoxic preconditioning reduces reoxygenation injuries via PI3K in respiratory muscle

Abstract

Reperfusion of hypoxic skeletal muscle adversely affects muscle function. Currently, there is no effective method to prevent this damage. In heart research, these injuries may be attenuated by preconditioning treatment. However, little attention is paid to the therapeutics of skeletal muscle reperfusion injuries. This study tested the hypothesis that hypoxic preconditioning (HPC) preserves skeletal muscle function during reoxygenation. Isolated mouse diaphragm strips were stimulated in a contractile chamber containing hypoxic or normoxic Ringer’s solution. Intracellular reactive oxygen species (ROS) generation was measured using the fluorescent probe dihydrofluorescein with confocal microscopy. Our results demonstrated that HPC increased the muscle’s resistance to fatigue during reoxygenation (P < 0.05). Phosphatidylinositol-3-kinase (PI3K) inhibition (LY 294002) abolished the HPC effect. Furthermore, confocal studies showed that ROS formation during reoxygenation was diminished by HPC. Therefore, HPC may exert its protection on skeletal muscle through the activation of PI3K and blockage of ROS formation during a reoxygenation period.