The effects of nitric oxide inhibition on regional hemodynamics during hyperdynamic endotoxemia
J. L. Henderson, R. Statman, J. N. Cunningham, W. Cheng, P. Damiani, A. Siconolfi and J. H. Horovitz
Department of Surgical Research, Maimonides Medical Center, Brooklyn, NY.
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
endotoxin-treated 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 carotid 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.
