Nitric oxide inhibition improved myocardial metabolism independent of tissue perfusion during ischemia but not during reperfusion.
Nitric oxide (NO) is one of the important regulators of cardiac metabolism and function as well as of tissue perfusion. Myocardial NO formation is increased during ischemia and reperfusion. We investigated the roles of endogenous NO in myocardial metabolism during ischemia and reperfusion independent of tissue perfusion changes. In an open-chest pig model, a bolus infusion of 20 mg/kg of N(G)-nitro l -arginine methyl ester (l -NAME), a NO synthase inhibitor, did not alter the regional myocardial perfusion compared with a control saline injection, as measured by colored microsphares. Using(31)P-nuclear magnetic resonance spectroscopy, we showed that the tissue levels of pH and adenosine triphosphate (ATP) but not those of creatine phosphate were significantly preserved in the l -NAME group compared with the placebo group during the subsequent 15-min regional ischemia. Thus, l -NAME reduced myocardial ATP utilization during ischemia, and the mechanism underlying these effects is independent of tissue perfusion changes. However, l -NAME did not accelerate the recovery of ATP levels following reperfusion, suggesting distinct roles of endogenous NO during reperfusion.
Araki
M
M
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tanaka
M
M
Hasegawa
K
K
Yokota
R
R
Maeda
T
T
Ishikawa
M
M
Yabuuchi
Y
Y
Sasayama
S
S
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D013552:Swine; D014693:Ventricular Fibrillation / Q000401:mortality
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester