0420: Acute exercise preconditioning induced mitochondrial protection against skeletal muscle ischemia–reperfusion injury

Abstract

Ischemia-reperfusion (I-R) induces mitochondrial function impairments and oxidative stress in skeletal muscle. In cardiac muscle, one-to-several days of exercise attenuate I-R injury. The objective of the present study was to show that a single exercise (EXO) prior to the I-R period protects the hind limb mitochondrial function. Twenty mice were randomly divided into 2 groups: The control group (CTL I-R, n=10) underwent I-R without exercise and the exercise group (EXO I-R, n=10) ran before I-R. Mice underwent 2 hours of ischemia induced by a rubber band tourniquet applied on the right root of the hind limb (the left leg was used as control leg), followed by a reperfusion period of 2 h. The EXO was performed on a treadmill with 10% incline 1h before I-R. The mice ran at a speed of 30cm until 40cm/sec during 30min. Blood lactate obtained from the tip of the tail at the end of EXO was above 9 mmol/L. In skinned gastrocnemius fibers, I-R significantly decreased the maximal mitochondrial respiration (Vmax) of the ischemic leg in comparison to the control leg in the CTL group (23.6 vs 28.6 pmol/(sec*mg wet weight); p<0.05). EXO I-R mice increased Vmax in comparison to CTL I-R mice (39.5 vs 31.8 pmol/(sec*dw) in the ischemic leg and the control leg respectively; p<0.05)). After EXO, the impairment between ischemic leg and control leg was partially restored (p=0.22). Without preconditioning, I-R increased H202 production of the ischemic leg in comparison to the control leg (42.6 vs 37.8 umol/mg dw; p=0.23). EXO I-R mice significantly decreased the H202 production in comparison to CTL I-R mice (26.6 vs 42.6 umol/mg dw; p<0.01) in the ischemic leg. After EXO, the impairment between ischemic leg and control leg was completely abolished (p=0.8). These results show that a preconditioning exercise protect the maximal mitochondrial respiration in mice and reduce the mitochondrial production of ROS following a period of I-R.