Am. J. Respir. Crit. Care Med., Vol 150, No. 6, Dec 1994, 1539-1544.
Modulation of hemodynamics and organ blood flow by nitric oxide synthase inhibition is not altered in normotensive, septic rats
CM Martin and WJ Sibbald
A.C. Burton Vascular Biology Laboratory, Victoria Hospital, London, Ontario, Canada.
Hyperdynamic sepsis is associated with a redistribution of organ blood
flow. We hypothesized that increased nitric oxide (NO) production could
mediate this process. The objective of this study was to determine the
effect of a NO synthesis inhibitor on systemic and organ blood flows in
vivo in septic and in normal rats. Rats were instrumented for hemodynamic
monitoring and randomized to undergo cecal ligation and perforation (CLP)
or control laparotomy. Cardiac output and organ blood flow were measured by
thermodilution and radioactive microspheres, respectively. Baseline values
were obtained at 24 h after CLP or control laparotomy and after the
administration of L-nitro-arginine methyl ester (L-NAME) at 2, 4, 8, and 16
mg/kg intravenously. All studies were performed in awake, unrestrained
animals. Septic animals were normotensive and hyperdynamic. L-NAME
decreased cardiac index and increased systemic vascular resistance and mean
arterial blood pressure to an equivalent degree in control and in CLP
animals. CLP was associated with significantly increased relative blood
flow to the small bowel and portal circulation. Although cardiac output
decreased with L-NAME, blood flow to the diaphragm, liver, and brain was
relatively well preserved. Absolute blood flow to other organs, including
small bowel, decreased in parallel to the cardiac output. The effect of
L-NAME on organ blood flow was comparable in control and in CLP animals. We
conclude that the influence of NO on organ blood flows appears to vary
between organs, but that NO does not explain the redistribution of blood
flow observed in hyperdynamic sepsis.
