Attenuation of oxidant damage in the postconditioned heart involves non-enzymatic response and partial catalytic protection

Oxidant stress, among other effectors, is implicated in the sequel of myocardial reperfusion injury. It is generally accepted that maintaining the balance between oxidant and antioxidant signalling within the cell provides protection against reperfusion damage. The cardioprotective strategy of postconditioning (PC) reduces reperfusion injury through complex mechanisms; however, the contribution of the antioxidant system has not been fully investigated. In this study, isolated rat hearts were subjected to PC after 30 min global ischaemia, and then to 5 min (IR5) or 60 min of reperfusion (IR60). Postconditioning significantly increased the left ventricular developed pressure and the double product (heart rate × left ventricular developed pressure) for both early (PC5) and prolonged reperfusion (PC60, PC before 60 min of reperfusion). Necrotic tissue diminished to 10.8% in PC60 hearts, compared with 49% of infarct size measured in IR60 hearts (P < 0.05 versus IR60). Also, protein carbonylation and malondialdehyde levels decreased and were correlated with a significant augmentation in CuZn superoxide dismutase activity (P < 0.05, PC60 versus IR60) and increased glutathione redox state (GSH:GSSG ratio; P < 0.05, PC60 versus IR60). Diethylthiocarbamate, a non-selective superoxide dismutase inhibitor, significantly diminished the protection afforded by PC when administered throughout the protocol. However, administration of this inhibitor only during reperfusion had no effect on PC-induced cardioprotection. These results indicate that non-enzymatic antioxidants account for the protective effect of PC, modifying the oxidant stress caused by ischaemic reperfusion in rats. The contribution of CuZn superoxide dismutase activity in the observed cardioprotective effect is less clear, and could be relevant if acting in concert with other PC-activated mechanisms.