OXYGEN-FREE RADICALS AND CARDIAC DEPRESSION

The present investigation deals with the in vivo effects of oxygen free radicals (OFRs) in the absence and presence of scavengers of OFRs (superoxide dismutase, SOD, and catalase) on the cardiac function and contractility and with the in vitro effects of exogenous OFRs and various pH and pO(2) on the release of acid hydrolases from dog myocardial lysosomes. The hemodynamic measurements were made before and at various intervals after administration of OFRs for up to 2 h. Xanthine plus xanthine oxidase (X-XO) and opsonized zymosan were used to generate OFRs. Oxygen free radicals produced a decrease in the cardiac function and indices of myocardial contractility. SOD alone or in combination with catalase tended to protect the cardiac function against the deleterious effects of OFRs. There was about a threefold increase in the release of cathepsin D activity in vitro from the lysosomes in the preparations treated with X-XO as compared to those without such treatment. The presence of SOD prevented the release of cathepsin D from the lysosomes. The changes in pH (4.5, 5.5, 6.0, 6.5, 7.4, 8.0) alone did not cause any increase in the enzyme release. However, the presence of OFRs at each pH resulted in a similar increase (about threefold) in the release of cathepsin D. Similarly the changes in pO(2) alone did not cause the release of cathepsin D, but there were marked increases in the release of cathepsin D at each pO(2) in the presence of OFRs. These data indicate that it is the oxygen free radicals and not the alterations in pH or pO(2) that are primarily responsible for the release of lysosomal hydrolases. OFRs, in addition to their direct myocardial damaging effect, may also be responsible for the cardiac damage through the release of lysosomal enzymes. These results suggest that OFRs are a cardiac depressant in addition to causing cellular damage. Scavengers of OFRs may be beneficial in counteracting the deleterious effects of OFRs on the hemodynamic parameters and cellular integrity.