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 facility in Brooklyn, NY.
Participants
Eleven mongrel dogs.
Intervention
Eleven dogs were divided into one of two groups: a control group (n=5) and an endotoxintreated group (n=6). The animals were anesthetized, and 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 injection 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 NG-monomethyl-L-arginine. After 15 minutes of inhibition, a 400-mg/kg intravenous administration of L-arginine, the substrate of NO synthase enzyme, was given. Physiologic measurements were continued for 15 minutes thereafter.
Main Outcome Measures
Heart rate, blood pressure, central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, hematocrit, arterial and venous blood gas values, and blood flow measurements of right internal cartoid artery, superior mesenteric artery, left renal artery, and distal aorta.
Results
Control animals did not demonstrate a significant (P>.05) decrease in blood flow in the internal carotid artery, superior mesenteric artery, and distal aorta after the administration of NG-monomethyl-L-arginine. The endotoxin-treated group showed a significant (P<.05) decrease in organ perfusion when treated with the NO synthase inhibitor, NG-monomethyl-L-arginine.
Conclusions
Inhibition of NO production 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.
(Arch Surg. 1994;129:1271-1275)
