Endothelium bound extracellular superoxide dismutase type C reduces damage in reperfused ischaemic rat hearts.

OBJECTIVE: The aim was to determine if endothelium associated extracellular superoxide dismutase type C (EC-SOD C) exerts any protective effect against cardiac damage induced by ischaemia and reperfusion. METHODS: Langendorff perfused rat hearts were subjected to 15 min global ischaemia followed by reperfusion. Prior to the ischaemia the hearts were perfused for 15 min with a buffer containing recombinant human EC-SOD C (rh-EC-SOD C, 20 mg.litre-1), or the corresponding vehicle, followed by extensive perfusion with SOD free medium. RESULTS: In hearts receiving the vehicle, reperfusion was associated with a marked release of creatine kinase into the effluent 28 (SEM 1.5) IU.15 min-1, n = 5] and coronary flow measured 15 min after initiation of reperfusion was reduced by 68% compared to preischaemic flow. In hearts pretreated with EC-SOD C but washed with enzyme free buffer before being subjected to ischaemia, the creatine kinase release was significantly smaller, at 14(2.1) IU.min-1, n = 5 (p less than 0.001), and the reduction in coronary flow less extensive (54%, p less than 0.05, v vehicle). To demonstrate the binding of EC-SOD C to the endothelium, heparin, which releases EC-SOD C from the endothelial surfaces, was added to the perfusate 30 min after initiation of reperfusion. The same amount of EC-SOD C was released to the effluent from previously ischaemic hearts (12.4(2) micrograms)] as from hearts not subjected to ischaemia (13.8(1.4) micrograms)]. CONCLUSIONS: Recombinant human EC-SOD type C bound to the endothelial surface reduces the cardiac damage associated with ischaemia and reperfusion. The protective effect was evident both in terms of a reduction of biochemical markers of injury and a better preservation of postischaemic coronary flow. Furthermore, ischaemia and subsequent reperfusion did not cause any alteration in the binding capacity of EC-SOD C to the cardiac vasculature.