The role of L-arginine in ameliorating reperfusion injury after myocardial ischemia in the cat.
BACKGROUND
Myocardial ischemia followed by reperfusion results in endothelial dysfunction characterized by a reduced release of endothelium-derived relaxing factor (EDRF). Because EDRF has been characterized as nitric oxide, we examined the ability of L-arginine, the substrate for nitric oxide synthesis, to protect in a feline model of myocardial ischemia plus reperfusion.


RESULTS
The effects of L-arginine were investigated in a 6-hour model of myocardial ischemia and reperfusion in pentobarbital-anesthetized cats. A bolus administration (30 mg/kg) of L-arginine, or its enantiomer D-arginine, was given followed by a continuous infusion of 10 mg/kg/min for 1 hour starting 10 minutes before reperfusion. Myocardial ischemia plus reperfusion in cats receiving D-arginine resulted in severe myocardial injury and endothelial dysfunction characterized by marked myocardial necrosis, high cardiac myeloperoxidase activity in ischemic cardiac tissue, and loss of acetylcholine- and A-23187-induced endothelium-dependent relaxation in coronary artery rings. In contrast, myocardial ischemia plus reperfusion cats treated with L-arginine exhibited a reduced area of cardiac necrosis (16 +/- 2% versus 41 +/- 5% of area at risk, p less than 0.01), lower myeloperoxidase activity in the ischemic region (0.3 +/- 0.08 versus 0.8 +/- 0.10 units/100 mg tissue, p less than 0.05), and significant preservation of acetylcholine- (p less than 0.01) and A-23187- (p less than 0.01) induced endothelial-dependent relaxation.


CONCLUSIONS
These results demonstrate the ability of L-arginine to reduce necrotic injury in a cat model of myocardial ischemia plus reperfusion, and this reduction in infarct size is associated with the preservation of endothelial function and attenuation of neutrophil accumulation in ischemic cardiac tissue.
Weyrich
A S
AS
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa. 19107-6799.
Ma
X L
XL
Lefer
A M
AM
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002415:Cats; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism
D001120:Arginine; D009195:Peroxidase