THE PROTECTIVE EFFECT OF L-ARGININE ON MYOCARDIAL INJURY AND ENDOTHELIAL FUNCTION FOLLOWING ISCHEMIA AND REPERFUSION IN THE PIG

The protective effect of the nitric oxide (NO) substrate L-arginine on myocardial ischaemia/reperfusion injury was studied in pigs. Four groups were subjected to 45 min ischaemia and 4h 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 (1mg.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.