MYOCARDIAL PROTECTION Enhancement of recovery of myocardial function by oxygen freeradical scavengers after reversible regional ischemia

Reperfusion after reversible regional ischemia has been shown to result in delayed recovery of myocardial function, but the mechanism responsible for this phenomenon remains unknown. We explored the potential role of oxygen-free radicals as mediators of postischemic dysfunction in open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery (LAD) followed by 2 hr of reperfusion. Treated animals (n = 19) received an infusion of the oxygen free-radical scavengers superoxide dismutase (SOD; 15,000 U/kg) and catalase (CAT; 55,000 U/kg) for 1 hr starting 15 min before LAD occlusion, while control animals (n = 20) received an equal volume of saline. SOD and CAT produced no discernible effect on heart rate, aortic pressure, or left atrial pressure. Collateral flow to the ischemic zone (radioactive microspheres) was 0.07 + 0.01 ml/min/g in both groups. The size of the occluded bed as determined by postmortem perfusion was 26.1 + 1.2% of the left ventricle in the control group and 26.5 + 0.9% in the treated group. Systolic wall thickening (an index of regional function) was assessed with an epicardial pulsed-Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesia during ischemia. Nevertheless, recovery of function (expressed as percent of baseline) was considerably greater in the treated dogs, both at 1 hr (43.8 + 14.3 vs 12.8 11.6) and 2 hr of reperfusion (74.2 8.4 vs 31.6 + 9.8, p < .005). This improved recovery of function obtained with SOD and CAT suggests that oxygen-free radicals play an important role in the genesis of myocardial dysfunction after a brief episode of regional ischemia. Circulation 72, No. 4, 915-921, 1985. REPERFUSION after a brief period of experimental coronary artery occlusion results in delayed recovery of regional function despite the absence of myocardial cell necrosis. 1 The mechanism underlying this persistent but ultimately reversible dysfunction, or myocardial "stunning,"' remains unclear. There is, however, mounting evidence to implicate oxygen-free radicals; as mediators of reperfusion injury in various organ systems, including the heart.6 These byproducts of oxygen metabolism, which include the superoxide anion (0-2), hydrogen peroxide (H202), and the hydroxyl radical (OHR), are highly reactive substances capable From the Experimental Animal Laboratory, Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston. Address for correspondence: M. L. Myers, M.D., 375 South St., Victoria Hospital, London, Ontario, Canada N6A 4G5. Received April 1, 1985; revision accepted July 12, 1985. This study was carried out during Dr. Myers' tenure as a Fellow of the Medical Research Council of Canada. The results were presented in part at the thirty-fourth meeting of the American College of Cardiology, Anaheim, CA, March, 1985. Vol. 72, No. 4, October 1985 of producing marked cellular damage. It has recently been shown that administration of the oxygen free-radical scavengers superoxide dismutase (SOD), a scavenger of the superoxide anion, and catalase (CAT), a scavenger of hydrogen peroxide, results in a significant decrease in infarct size in a canine preparation of 90 min of coronary artery occlusion.7 Furthermore, free-radical scavengers have been reported to improve global ventricular function after prolonged hypothermic ischemic arrest.8-10 Results obtained in such preparations of irreversible ischemic injury, or prolonged global ischemia, cannot necessarily be extrapolated to the setting of a brief episode of regional ischemia. Thus, the role of oxygen-free radicals in the pathogenesis of postischemic dysfunction after transient coronary occlusion remains unknown. Accordingly, the present study was undertaken to determine whether the free-radical scavengers SOD and CAT could enhance recovery of function after reversible regional ischemia in open-chest dogs 915 by gest on Jauary 3, 2018 http://ciajournals.org/ D ow nladed from