EFFICACY OF A HYDROXYL RADICAL SCAVENGER (VF-233) IN PREVENTING REPERFUSION INJURY IN THE ISOLATED RABBIT HEART

We tested the hypothesis that 3,4,5,-trihydroxybenzamidoxime (VF 233), a demonstrated hydroxyl radical scavenger and an effective Fe3+ chelator, attenuates reperfusion injury and improves isovolumic left ventricular function. Eighteen isolated, perfused rabbit hearts with intracavitary balloons were subjected to normothermic, global ischemia until the initiation of ischemic contracture. Effects on the adenine nucleotide pool metabolites were determined by high-pressure liquid chromatography from right ventricular biopsy specimens before ischemia and at 15-minute intervals throughout reperfusion. In the experimental group (n = 9), a 5-mL bolus of 1 mol/L VF 233 was given immediately before reperfusion and followed by a continuous infusion (0.125-mu-mol/min). The control group (n = 9) received the vehicle solution at identical times. Rabbits treated with VF 233 had significant improvement in left ventricular function (expressed as percent return of left ventricular peak developed pressure) within 15 minutes of reperfusion (55.0 +/- 3.0 versus 66.2 +/- 4.1; p < 0.05 by analysis of variance) after global ischemia and remained significantly improved throughout the reperfusion period. Myocardial adenine nucleotide pool intermediates were not significantly different between groups. These results demonstrate that administration of VF 233 significantly improves ventricular function but does not affect adenine nucleotide metabolism after ischemia and reperfusion.