Prevention of Reperfusion Syndrome in Acute Muscular Ischaemia with Free Radical Scavengers and Membrane-Protecting Compounds: An Experimental Study

Abstract

The prevention of oxidant-induced damage following reperfusion was experimentally evaluated. Two pharmacological regimens containing different combinations of antioxidant factors and membrane-stabilizing compounds, such as α-tocopherol (vitamin E), methionine, dexamethasone, mannitol and cysteine, were administered. The reduced/oxidized glutathione (GSH/GSSG) ratio in muscle was used to evaluate oxidative stress. Ischaemia was induced by occluding the aorta and the inferior vena cava with an irrigation-occlusion catheter. After 4h of ischaemia, five sheep were reperfused without any treatment (control group) and five treated with an endoaortic bolus administered at declamping (treatment 1). In five other sheep, treatment started during ischaemia (treatment 2). Ischaemia and, in particular, reperfusion significantly reduced the muscle GSH content, compared with the basal value in the control group; thus the GSH/GSSG ratio decreased significantly in the control group from 10.5(2.2) (mean(s.e.) basal value) to 0.687(0.3) at reperfusion (P<0.009). Both treatments 1 and 2 significantly prevented a reduction in GSH content induced by reperfusion following ischaemia; the GSH/GSSG ratio (10.5(2.2) basal value) increased to 19.67(4.6) with reperfusion in the treatment group 1, mainly because of a lower decrease of GSH and a lower level of GSSG while it did not change in treatment group 2 (10.7(5.0)). Levels of creatine phosphokinase did not change in the treated groups, although they increased significantly in the control group (P<0.006). Although oxidative stress is not the only cause of damage in revascularization, this study confirms the protective ability of treatment with free radical scavengers and membrane-stabilizing compounds.