The protective effect of L-arginine on myocardial injury and endothelial function following ischaemia and reperfusion in the pig.
The protective effect of the nitric oxide (NO) substrate L-arginine on myocardial ischaemial/reperfusion 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.
Pernow
J
J
Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.
Uriuda
Y
Y
Wang
Q D
QD
Li
X S
XS
Nordlander
R
R
Rydeén
L
L
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000502:physiology; D013552:Swine
D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine