Significance of nitric oxide in hemorrhage-induced hemodynamic
alterations, organ injury, and mortality in rats.
Yao, Yong-Ming, Soheyl Bahrami, Guenther Leichtfried, Heinz Redl, and
Guenther Schlag.
Ludwig Boltzmann Institute for Experimental and Clinical
Traumatology, A-1200 Vienna, Austria
APStracts 2:0465H, 1995.
In an attempt to evaluate the role of nitric oxide (NO) in
pathophysiologic alterations, and multiple organ damage caused by
hemorrhagic shock, we employed NG-monomethyl-L-arginine (L-NMMA), an
inhibitor of NO synthase, in anesthetized rats subjected to a
prolonged hypovolemic insult (30-35 mm Hg for 180 min). Infusion of
2.0 mg/kg L-NMMA at the end of resuscitation diminished the fall in
mean arterial pressure (MAP), significantly increased the cardiac
index (CI) and stroke volume (SV), together with remarkable
protection from multiple organ damage compared to the controls. The
48 h survival rate was significantly improved from 26.7% in the
control group to 68.8% in the treatment group (P<0.05). In
contrast, the high dose of 20.0 mg/kg L-NMMA resulted in a strong
blood pressure response but a marked reduction in CI and SV
concomitant with an increased total peripheral resistance index
(TPRI) within the observation period, and tended to increase damage
to various organs at 2 h after treatment. In addition, marked
elevation in both endotoxin and tumor necrosis factor (TNF) levels
were observed in animals subjected to shock insult. The results
suggest that NO induced by hemorrhagic shock in rats is an important
mediator for pathophysiologic alterations associated with
cardiovascular abnormalities, multiple organ dysfunction, and even
lethality. Regulation of NO generation and use of NO inhibitors might
provide new aspects in the treatment of hemorrhage related disorders,
while the administration of L-NMMA would be either deleterious or
salutary in a dose dependent manner.
Received 6 March 1995; accepted in final form 27 September 1995.
APS Manuscript Number H205-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95