The effects of high dose N(G)-nitro-L-arginine-methyl ester on myocardial blood flow and left ventricular function in dogs

Rubin I. Cohen*, Ling Chen, Steven M. Scharf

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Purpose: 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 N(G)-nitro-L-arginine-methyl ester (L-NAME) to those of 300 mg/kg and assess the effects on coronary ischemia and myocardial function. Materials and 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) end 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 acidocis. 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.

Original languageEnglish (US)
Pages (from-to)206-213
Number of pages8
JournalJournal of Critical Care
Volume11
Issue number4
DOIs
StatePublished - Dec 1996

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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