Effect of iloprost on contractile impairment and mitochondrial degeneration in ischemia-reperfusion of skeletal muscle

Abstract

Purpose Acute lower extremity ischemia is still a main cause of mortality and morbidity in orthopedic traumatology and reconstructive surgery. In acute lower extremity ischemia, the skeletal muscles are the tissues that are the most vulnerable to ischemia. The aim of this study was to evaluate the effects of iloprost (IL) therapy on skeletal muscle contractile impairment and mitochondrial degeneration in an acute lower extremity ischemia-reperfusion rat model. Main Methods Forty Wistar albino rats were randomly divided into a control group and four experimental groups. Experimental groups were either subjected to 2 h of lower extremity ischemia followed by a 4-h reperfusion period or to 4 h of ischemia followed by an 8-h reperfusion period. Except for the animals in the control group, all animals received IL (1 ng/kg/min) or saline (1 ml/kg) by intraperitoneal infusion for 10 min immediately before reperfusion. At the end of the recording of skeletal muscle electrical activity and contractility, all rats were sacrificed by decapitation and muscle samples of lower extremity were immediately harvested for histopathologic analyses. Results After ischemia-reperfusion, a breakdown in the force–frequency curves of extensor digitorum longus muscle was observed, showing the diminished muscle contractility. However, IL significantly improved muscle contractility following injury induced by 2 h of ischemia followed by a 4-h reperfusion period. In addition, IL partially ameliorated mitochondrial degeneration in the muscle cells of ischemia groups. Conclusion This study indicates that immediate IL therapy repairs muscle damage especially after 2 h of ischemia and 4 h of reperfusion and therefore that IL improves contractile function.