The effects of high dose NG-nitro-L-arginine-methyl ester on myocardial blood flow and left ventricular function in dogs.
OBJECTIVE
Nitric oxide (NO) synthase inhibition has been reported to cause elevation in mean arterial pressure (MAP) and a decrease in cardiac index (CI), the cause of which is not completely understood. It has been shown that increased concentrations of NO synthase inhibitors cause a further drop in cardiac output without a corresponding increase in arterial pressure, prompting the conclusion that NO inhibition results in direct myocardial depression. However, myocardial ischemia was not completely ruled out as a cause for myocardial dysfunction in these studies. The purpose of this study was to examine the effects of 30 mg/kg of the NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) to those of 300 mg/kg and assess the effects on coronary ischemia and myocardial function.


METHODS
Eight anesthetized dogs underwent median sternotomy and pericardiectomy. L-NAME 30 mg/kg was administered and the effects were recorded at 5, 15, and 30 minutes. Thereafter, 300 mg/kg was administered and the effects were observed for 5, 15, and 30 minutes. We measured MAP, heart rate (HR), CI, left ventricle (LV) and systolic and diastolic pressures, the first derivative of LV pressure (dP/dt), left anterior descending artery blood flow, regional LV contraction, gas tensions, and lactates. A coronary sinus catheter allowed for measurements of coronary sinus pressure, lactate, and gas tensions. Stroke volume, percent myocardial shortening (dL/dt) myocardial oxygen consumption, and net lactate myocardial production were calculated.


RESULTS
Whereas 30 mg/kg had minimal effects on coronary blood flow and LV function, 300 mg/kg resulted in profound hypotension, drop in CI, and acidocsis.


CONCLUSIONS
L-NAME at 30 mg/kg caused a rise in MAP and systemic vascular resistance; however, it had no effect on ventricular function. High dose NO synthase inhibition causes myocardial depression not related to increased afterload, coronary vasoconstriction, or myocardial ischemia.
Cohen
R I
RI
Division of Pulmonary and Critical Care Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA.
Chen
L
L
Scharf
S M
SM
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics; D009200:Myocardial Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester