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

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.

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.

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)].

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.