The Pathogenesy And Protection Of Myocardial Injury During Skeletal Muscle Ischemia Reperfusion

Background and Objective: Skeletal muscle ischemia reperfusion (IR) is a common pathophysiological phenomenon clinically. Ischemia of the extremities is an unavoidable occurrence during peripheral vascular surgery, aortic aneurysm surgery, replantation of extremities, peripheral vascular injury or crushing syndrome. Recent studies have shown that skeletal muscle IR can trigger a systemic infammatory response syndrome (SIRS). It causes not only local tissue injury, but also remote organs dysfunction including heart, liver, lung, kidney and small intestine. Clinical studies suggest that the heart is at high risk in the setting of SIRS. The mechanism of acute myocardial injury following skeletal muscle IR is very complicated, up to now, not completely elucidated yet.In the present study, we have established the model of bilateral hindlimb ischemia and reperfusion in rats by using a tourniquet. Our experiment is divided into two parts. Firstly, we explore the role of the neutrophils and inflammatory cytokines, oxidant-antioxidant system, aldosterone (ALD) and endogenous hydrogen sulfide (H₂S)/cystathionine-γ-lyase (CSE) system in the pathogenesy of myocardial injury during skeletal muscle IR. Secondly, we are to ascertain the protective effects of exogenous H2S on the myocardial injury during skeletal muscle IR.Methods: In the first part, sixty-two Wistar rats were divided into 9 groups at random: Group normal (C), Group 2h ischemia (I2), Group 4h ischemia (I4) and Groups 4 h ischemia with 0.5h(R0.5), 2 h(R2), 4 h(R4), 6 h(R6),12 h(Ri2), 24 h(R.24) reperfusion. In the second part, thirty Wistar rats with 4h reperfusion following 4 h ischemia were divided into 4 groups: Group IR, Group H2S: IR+ inhaling 80ppm H2S, Group NaHS: IR+NaHS 0.78mg/kg ip, Group PPG: IR+ DL-propargylglycine ( PPG) 50mg/kg ip. The pathologic changes in the myocardium were observed. The plasma levels of H2S, CK-MB, TNT, myeloperoxidase (MPO), tumor necrosis factor-a (TNF-α), malondialdehyde(MDA), total superoxide dismutase (T-SOD) , copper/zinc superoxide dismutase (CuZn-SOD) and ALD in each group were measured. The CSE activity, T-SOD, CuZn-SOD activity and the levels of MPO, TNF-α, MDA, ALD in myocardium were detected. T-SOD activity minus CuZn-SOD activity equals Mn-SOD activity. Immunohistochemistry technique was used to determine expression of TNF-α in myocardium.Results: Histopathologic results indicated myocardial injury were relatively light after skeletal muscle ischemia but it got much more serious following reperfusion. Compared with Group normal, the levels of CK-MB, MPO, TNF-α, MDA in plasma and the levels of MPO, TNF-α in myocardium were significantly increased in Group I2;the levels of T-SOD,CuZn-SOD in plasma and the level of CuZn-SOD in myocardium were significantly decreased in Group I2 (P<0.05);the plasma levels of TNT, ALD and the myocardial levels of MDA , ALD, Mn-SOD were markedly increased in Group Li(P<0.05). Compared with Group I4, the plasma levels of CK-MB, MPO and the myocardial level of Mn-SOD were markedly increased in Group Ro.5(P