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European Heart Journal 1994 15(12):1712-1719;
Copyright © 1994 by the European Society of Cardiology.
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© 1994 The European Society of Cardiology

The protective effect of L-arginine on myocardial injury and endothelial function following ischaemia and reperfusion in the pig

J. PERNOW, Y. URIUDA, Q-D. WANG, X-S. LI, R. NORDLANDER and L. RYDEÉN

Department of Cardiology, Karolinska Hospital S-171 76 Stockholm, Sweden

Received 12 April 1994; accepted 5 July 1994.

Correspondence: Dr John Pernow, Department of Cardiology, Karolinska Hospital, S-171 76 Stockholm, Sweden.

Abstract

The protective effect of the nitric oxide (NO) substrate L-arginine on myocardial ischaemialreperfusion injury was studied in pigs. Four groups were subjected to 45 min ischaemia and 4 h reperfusion. One control group received coronary venous retroinfusion of saline, the second retroinfusion of L-arginine (1 mg. kg–1. min–1), the third retroinfusion of L-arginine plus the NO synthase inhibitor N{omega}-nitro-L-arginine (L-NNA), and the fourth systemic i.v. infusion of L-arginine (1 mg. kg–1. min–1). The infarct size in the L-arginine retroinfusion group was 35 ± 5% of the myocardial area at risk compared to 76 ± 5% in saline treated controls (P<0.001). In pigs receiving the combination of retroinfused L-arginine and L-NNA the infarct size was similar to that of controls (79 ± 4%). Systemic i.v. infusion of L-arginine did not influence the infarct size. Administration of L-NNA + L-arginine slightly increased arterial blood pressure during ischaemia but the groups did not differ in blood pressure, heart rate, rate-pressure product, left ventricular dP/dt or coronary blood flow during the reperfusion period. Coronary vasodilatation by acetylcholine was significantly compromised in the saline retroinfusion group, but not in the L-arginine retroinfusion group as compared to pigs not subjected to myocardial ischaemia. The results show that coronary venous retroinfusion of L-arginine reduces myocardial infarct size and preserves endothelial function via a local action which seems to be related to maintained nitric oxide formation.

Key Words: L-arginine • endothelium • ischaemia/reperfusion • myocardial infarct • nitric oxide • vasodilatation


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