Cardiac depressant effects of oxygen free radicals

In many clinical situations, including cardiac ischemia/reperfusion, elective cardiac arrest, and renal dialysis, the chances of increased production of oxygen free radicals (OFR) exist. OFR have been implicated as a causative factor of cell damage in several pathologic conditions. The effects of exogenous OFR, generated by xanthine plus xanthine oxidase, in the absence and in the presence of OFR scavenger (superoxide dismutase [SOD]) on the contractility of isolated perfused heart of rabbit were studied. OFR produced concentration-dependent decreases in the contractility of perfused heart. SOD prevented the OFR-induced decreases in the left ventricular contractility. Xanthine produced an increase in the contractility of isolated perfused rabbit's heart. Xanthine oxidase produced a marked decrease in the left ventricular contractility. Repeated administration of xanthine oxidase produced accelerated and greater decreases in the contractility of perfused heart when compared with that of the initial administration of the drug. Effects of xanthine or xanthine oxidase on the cardiac function and contractility were also studied in anesthetized dogs. Xanthine alone had no significant effect on the cardiac function and indices of myocardial contractility. However, xanthine oxidase produced a marked decrease in the mean aortic pressure, left ventricular work index, heart rate, cardiac index, left ventricular systolic pressure, left ventricular end-diastolic pressure, (+) and (-) dp/dt of left ventricular pressure, and other indices of myocardial contractility [(dp/dt)/PAW (pulmonary arterial wedge pressure)]; and an increase in the total systemic and pulmonary vascular resistance. Repeated administration of xanthine oxidase in anesthetized dogs had lesser effects on the cardiovascular system when compared with those from the initial dose of the drug. These results suggest that OFR are cardiac depressant. Clinical situations wherein there is an increased production of OFR or increased formation of xanthine and xanthine oxidase may be associated with decreased cardiac function and contractility. Scavengers of OFR may protect the heart from the deleterious effects of OFR in such clinical conditions.