Superoxide dismutase plus catalase improve contractile function in the canine model of the 'stunned myocardium'

Abstract

Fifteen minutes of coronary occlusion followed by reperfusion does not result in myocardial necrosis; however, the contractile function and high energy phosphate content of the previously ischemic myocardium remains depressed or 'stunned' for several hours to days after reperfusion. Oxygen-derived free radicals have been implicated in ischemia and reperfusion-induced injury in a variety of tissues. We wished to determine whether administration of free radical scavengers superoxide dismutase plus catalase before and during occlusion, and throughout reperfusion, could attenuate the 'stunning' produced by 15 minutes of left anterior descending coronary artery occlusion in anesthetized, open-chest dogs. Segment shortening in the previously ischemic zone recovered to within only ±10% of preinfusion values in the control group during 3 hours of reperfusion, while, in the treated dogs, segment shortening returned to a maximum of 56 ± 16% of preinfusion at 1 1/2 hours post-reperfusion (P < 0.0003 compared to controls). Similarly, superoxide dismutase + catalase-treated dogs exhibited improved wall thickening during reperfusion (+30% to +70% of preinfusion values), compared to controls (0% to +10%). However, this improvement in contractile function in the treated group was not accompanied by increased adenosine triphosphate stores in the previously ischemic zone (31.8 ± 0.8 vs. 28.2 ± 2.2 nmol/mg protein for control vs. treated groups). Infusion of superoxide dismutase + catalase did not influence blood flow during occlusion or reperfusion. However, the treated group did exhibit a significant decrease in blood pressure during reperfusion. Hypotension during reperfusion did not appear to be the cause of the improved contractile function, as administration of sodium nitroprusside (an afterload-reducing agent with no free radical scavenging properties) to an additional group of dogs during reperfusion had no significant effect on segment shortening in the previously ischemic tissue. Thus, treatment with free radical scavengers significantly enhanced function, but did not improve high energy phosphate content, in the stunned myocardium.