Aprotinin ameliorates ischemia/reperfusion injury in a rat hind limb model

The aim of the study was to investigate the protective effect of aprotinin in a rat hind limb ischemia/reperfusion (I/R) model. A well-known antioxidant, alpha-tocopherol, was also tested for comparison. Ischemia was induced for 4 h by vascular clamping of the iliac arteries of 24 Sprague-Dawley rats, followed by 1 h of reperfusion. Muscle injury was evaluated in three groups: a saline group, an alpha-tocopherol group and an aprotinin group. Blood pH, pO2, pCO2, HCO3, creatine kinase (CPK), lactate dehyrogenase (LDH) and thiobarbituric acid reactive substances (TBARS) as well as muscle TBARS were measured at the end of the reperfusion. Muscle tissue samples were taken for histological examination. alpha-Tocopherol and aprotinin groups showed a significant amelioration of plasma CPK (p=0.002, p=0.002), LDH (p=0.004, p=0.004) and muscle tissue TBARS (p=0.001, p=0.001) compared with the control. Plasma TBARS were significantly lower in the aprotinin group compared with the control (p=0.017). Also, tissue TBARS was significantly lower in the aprotinin group than the alpha-tocopherol group (p<0.001). Neutrophil infiltration was less prominent in the alpha-tocopherol and aprotinin groups compared to the control (p=0.006, p=0.001). These results suggest that aprotinin, a potent anti-inflammatory drug, is more useful than alpha-tocopherol, a powerful antioxidant, for attenuating muscle injury after I/R.