Extracellular-Superoxide Dismutase Type C (EC-SOD C) Reduces Myocardial Damage in Rats Subjected to Coronary Occlusion and 24 Hours of Reperfusion

Abstract

Extracellular-superoxide dismutase type C (EC-SOD C) is a secretory SOD isoenzyme which, in contrast to the intracellular CuZn SOD, has affinity to the endothelium and a long vascular half-life. In the present study, the effects of EC-SOD C and CuZn SOD on reperfusion-induced myocardial damage were determined in rats subjected to 10 min of left coronary artery ligation followed by 24 h of reperfusion. Recombinant human EC-SOD C (rh-EC-SOD C) or the corresponding volume of the vehicle was administered after completion of the coronary ligation. CuZn SOD was given in two equal doses, the first dose directly after ligation and the second one 6 h later. At the end of the reperfusion period the myocardial damage was quantified by measuring the creatine kinase concentration (CK) in the reperfused part of the left ventricular free wall (LVFW), and expressed as a percentage of the concentration in the non-ischemic septum. In the group given the vehicle, 47 ± 10 (mean ± SD) of the CK remained in the reperfused LVFW. In the rats receiving rh-EC-SOD C the corresponding values for each dose: 1.4, 4.2 and 12.6 mg/kg were 55 ± 12(ns), 55 ± 12(ns) and 65 ± 12% (p < 0.05, vs. vehicle, Dunnett's multiple comparison test), respectively. Administration of CuZn SOD (2 × 10mg/kg) resulted in 58 ± 16% (ns) CK remaining in the LVFW.

It is concluded that rh-EC-SOD C, unlike CuZn SOD, significantly reduced myocardial damage associated with ischemia and reperfusion, and that the myocardial protection was sustained after 24 h of reperfusion.

Key Words:

• Oxygen free radicals
• myocardial ischemia
• reperfusion
• superoxide dismutase
• infarct size