A comparison between the acute effects of nitric oxide synthase inhibition and fluid resuscitation on myocardial function and metabolism in entotoxemic dogs

Purpose: Nitric oxide (NO) synthase inhibitors increase mean arterial pressure (MAP) and systemic vascular resistance (SVR) in animal models of sepsis and in humans with septic shock. However, NO synthase inhibitors may cause coronary vessel constriction leading to myocardial ischemia and increased mortality in endotoxemic animals. This study was designed to test the acute effect of N-G-nitro-L-arginine (L-NAME) on left ventricular (LV) function and coronary blood flow in a dog model of endotoxemia. Methods: In open chest, anesthetized dogs endotoxemia was induced intravenously (IV) by Escherichia coli lipopolysaccharide at 2 mg/kg for 60 minutes. This resulted in hypotension, acidosis, and decreased SVR while cardiac index (CI) was maintained. When MAP was less than or equal to 60 mm Hg, animals were resuscitated with either dextran (group I), or L-NAME 30 mg/kg IV bolus (group II). Group III received L.-NAME only. A fourth group of dogs was given endotoxin and not resuscitated. Animals were followed up for 30 minutes after intervention. Animals in the fourth group were followed up until the MAP was approximately 30 mm Hg. Heart rate, CI, MAP, LV end systolic and diastolic pressures, dP/dt at a pressure of 40 mm Hg, left anterior descending artery coronary blood flow, regional LV contraction (sonomicrometer crystals), coronary pressures, gas tension, and lactates were continuously recorded. A catheter placed in the coronary sinus allowed measurement of coronary sinus pressure, as well as coronary sinus lactate and gas tensions. Stroke volume index, stroke work index, systemic vascular resistance index (SVRI), coronary vascular resistance, percent myocardial shortening, myocardial oxygen consumption (Mvo(2)) and net myocardial lactate production were calculated. Results: In Group I, fluid administration increased MAP, stroke work index, coronary blood flow, percent myocardial shortening, and Mvo(2). In Group II, L-NAME increased MAP to the same extent as fluid administration without evidence of coronary ischemia or myocardial dysfunction. L-NAME did not alter Mvo(2) in either endotoxemic or nonendotoxemic animals. In group III, L-NAME alone resulted in a significant increase in MAP and SVRI, but its effects on coronary blood flow and LV function were not significant. We did not observe net lactate production in any of the groups. Coronary blood flow increased out of proportion to Mvo(2) in group I animals. Conclusions: We conclude that although L-NAME at 30 mg/kg causes vasoconstriction, its effects on coronary blood flow and LV function were not significant. (C) 1996 by W.B. Saunders Company