Abstract
Myocardial reperfusion after reversible regional ischemia is known to result in delayed recovery of contractile function, but the mechanism responsible for this phenomenon remains unclear. We examined the ability of N-2-mercaptopropionylglycine, a synthetic thiol compound with oxygen free radical scavenging properties, to attenuate postischemic dysfunction in open chest dogs undergoing a 15 minute occlusion of the left anterior descending coronary artery followed by 4 hours of re-perfusion. Treated animals received an infusion of N-2-mercaptopropionylglycine (50 mg/kg per h) for 4 hours starting 15 minutes before coronary occlusion. Collateral flow, as determined with radioactive microspheres after 10 minutes of ischemia, was 0.07 ± 0.01 ml/min per g (mean ± SE) in both control (n = 20) and treated (n = 13) groups. The occluded vascular bed, as determined by postmortem perfusion, averaged 26.1 ± 1.2% of the weight of the left ventricle in control and 29.6 ± 1.3% in treated animals. 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 at 1 hour (44.6 versus 12.8%, p = 0.05), 2 hours (64.0 versus 31.6%, p < 0.02), 3 hours (77.1 versus 36.7%, p < 0.01) and 4 hours of reperfusion (75.0 versus 40.0%, p < 0.05). Thus, N-2-mercaptopropionylglycine produced a significant and sustained improvement in recovery of contractile function after a brief episode of regional myocardial ischemia. These results suggest that oxygen free radicals play a significant role in myocardial postishemic dysfunction. Because N-2-mercaptopropionylgly-cine is potentially available for oral prophylactic therapy, these results have significant therapeutic implications. © 1986, American College of Cardiology Foundation. All rights reserved.