A COMPARISON BETWEEN THE ACUTE EFFECTS OF NITRIC-OXIDE SYNTHASE INHIBITION AND FLUID RESUSCITATION ON MYOCARDIAL-FUNCTION AND METABOLISM INENTOTOXEMIC 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 inhib itors may cause coronary vessel constriction leading to myocardial isc hemia and increased mortality in endotoxemic animals. This study was d esigned to test the acute effect of N-G-nitro-L-arginine (L-NAME) on l eft ventricular (LV) function and coronary blood flow in a dog model o f endotoxemia. Methods: In open chest, anesthetized dogs endotoxemia w as induced intravenously (IV) by Escherichia coli lipopolysaccharide a t 2 mg/kg for 60 minutes. This resulted in hypotension, acidosis, and decreased SVR while cardiac index (CI) was maintained. When MAP was le ss than or equal to 60 mm Hg, animals were resuscitated with either de xtran (group I), or L-NAME 30 mg/kg IV bolus (group II). Group III rec eived L.-NAME only. A fourth group of dogs was given endotoxin and not resuscitated. Animals were followed up for 30 minutes after intervent ion. Animals in the fourth group were followed up until the MAP was ap proximately 30 mm Hg. Heart rate, CI, MAP, LV end systolic and diastol ic pressures, dP/dt at a pressure of 40 mm Hg, left anterior descendin g artery coronary blood flow, regional LV contraction (sonomicrometer crystals), coronary pressures, gas tension, and lactates were continuo usly recorded. A catheter placed in the coronary sinus allowed measure ment of coronary sinus pressure, as well as coronary sinus lactate and gas tensions. Stroke volume index, stroke work index, systemic vascul ar resistance index (SVRI), coronary vascular resistance, percent myoc ardial shortening, myocardial oxygen consumption (Mvo(2)) and net myoc ardial 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 increas ed 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-NA ME alone resulted in a significant increase in MAP and SVRI, but its e ffects 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 vasoc onstriction, its effects on coronary blood flow and LV function were n ot significant. (C) 1996 by W.B. Saunders Company