THE EFFECTS OF NITRIC BRIDE INHIBITION ON REGIONAL HEMODYNAMICS DURING HYPERDYNAMIC ENDOTOXEMIA

Objective: To determine the effect of the inhibition of nitric oxide ( NO) on selective organ blood flow in endotoxin-induced sepsis. Design: Nonrandomized, controlled experiment. Setting: Animal research facili ty in Brooklyn, NY. Participants: Eleven mongrel dogs. Intervntion: El even dogs were divided into one of two groups: a control group (n=5) a nd an endotoxin-treated group (n=6). The animals were anesthetized, an d electromagnetic and ultrasonic flow probes were placed on the distal aorta, right internal carotid artery, superior mesenteric artery, and left renal artery. Sepsis was induced with a 60-mg/kg intravenous inj ection of Escherichia coli endotoxin. When the arterial blood pressure decreased to less than 60 mm Hg despite adequate fluid resuscitation, NO synthesis was inhibited with a 25-mg/kg intravenous administration of N-G-monomethyl-L-arginine. After 15 minutes of inhibition, a 400-m g/kg intravenous administration of L-arginine, the substrate of NO syn thase enzyme, was given. Physiologic measurements were continued for 1 5 minutes thereafter. Main Outcome Measures: Heart rate, blood pressur e, central venous pressure, pulmonary artery pressure, pulmonary capil lary wedge pressure, cardiac output, hematocrit, arterial and venous b lood gas values, and blood flow measurements of right internal cartoid artery, superior mesenteric artery, left renal artery, and distal aor ta. Results: Control animals did not demonstrate a significant (P>.05) decrease in blood flow in the internal carotid artery, superior mesen teric artery, and distal aorta after the administration of N-G-monomet hyl-L-arginine. The endotoxin-treated group showed a significant (P<.0 5) decrease in organ perfusion when treated with the NO synthase inhib itor, N-G-monomethyl-L-arginine. Conclusions: Inhibition of NO product ion in the treatment of sepsis caused a significant decrease in blood flow to all vascular beds in vivo. The role, if any, of the inhibition of NO in the treatment of sepsis is questioned.