Abstract
We compared the effects of polyethylene glycol conjugated superoxide dismutase (PEG-SOD, plasma t1/2≥30 hrs) to the native form of the enzyme (N-SOD, t1/2=6 min) in protecting the ischemic/reperfused canine myocardium. Anesthetized, open chest, male mongrel dogs (n=14) underwent 6 hrs of left circumflex coronary artery occlusion and reperfusion for 24 hrs. A single dose of either PEG-SOD (1, 000 U/kg) or N-SOD (1, 000 U/kg) was given via the left atrium 15 min before occlusion, followed by a continuous infusion of an additional 1, 000 U/kg of the respective enzymes for 6.5 hrs ending 15 min after reperfusion. The animals were sacrificed 24 hrs after reperfusion.
Mean infarct size, determined 24 hrs after reperfusion, in the PEG-SOD group was smaller than that observed in the N-SOD group (47.1±2.9% vs 63.5±2.2% of area-at-risk; P<0.001) with no observed difference in the size of area-at-risk. Hemodynamic parameters and calculated rate-pressure-product, as well as regional myocardial blood flow, during ischemia between the groups did not differ and could not account for the effect of PEG-SOD.
The results suggest that the sustained presence of oxyradical scavenger activity is necessary to prevent rather than delay myocardial necrosis due to oxyradicals produced during the ischemia as well as the during the period of reperfusion.
