Circulation, Vol 86, 279-288, Copyright © 1992 by American Heart Association
AS Weyrich, XL Ma and AM Lefer
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. METHODS AND 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.
ARTICLES
The role of L-arginine in ameliorating reperfusion injury after myocardial ischemia in the cat
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa. 19107-6799.
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