L-arginine administration prevents reperfusion-induced cardiomyocyte hypercontracture and reduces infarct size in the pig

Objective: Stimulation of cGMP synthesis protects cardiomyocytes against re oxygenation-induced hypercontracture. The purpose of this study was to dete rmine whether L-arginine supplementation has a protective effect against re perfusion-induced hypercontracture and necrosis in the intact animal. Metho ds: Twenty-four Large-White pigs were randomized to receive either 100 mg/k g of L-arginine IV or vehicle 10 min before 48 min of coronary occlusion an d 2 h of reperfusion. Hemodynamic variables, coronary blood how and myocard ial segment length changes (piezoelectric crystals) were monitored. Postmor tem studies included quantification of myocardium at risk (in vivo fluoresc ein), infarct size (triphenyltetrazolium reaction), myocardial myeloperoxid ase activity and histological analysis. Systemic, coronary vein, and myocar dial cGMP concentration were measured in additional animals. Results: Admin istration of L-arginine had no significant effect in hemodynamics or corona ry blood flow. During reperfusion, myocardial cGMP content was reduced in t he LAD as compared to control myocardium (P = 0.02). L-Arginine increased m yocardial cGMP content and caused a transient increase in plasma cGMP conce ntration during the initial minutes of reperfusion (P = 0.02). The reductio n in end-diastolic segment length induced by reperfusion, reflecting hyperc ontracture, was less pronounced in the L-arginine group (P = 0.02). Infarct size was smaller in pigs receiving L-arginine (47.9+/-7.2% of the area at risk) than in controls (62.9+/-4.9%, P = 0.047). There: were no differences between groups in leukocyte accumulation in reperfused myocardium (P = 0.8 0). Conclusion: L-Arginine supplementation reduces myocardial necrosis seco ndary to in situ ischemia-reperfusion by a direct protective effect against myocyte hypercontracture. (C) 2000 Published by Elsevier Science B.V. All rights reserved.