Significance of tumor necrosis factor in hemorrhage-related
hemodynamic alterations, organ injury, and mortality in rats.
Bahrami, Soheyl, Yong-Ming Yao, Guenther Leichtfried, Heinz Redl, Ingo
Marzi, and Guenther Schlag.
Ludwig Boltzmann Institute for Experimental and Clinical
Traumatology, A-1200 Vienna, Austria, Department of Trauma Surgery,
University of Saarland, D-66421 Homburg/Saar, Germany
APStracts 3:0535H, 1996.
In order to evaluate the role of tumor necrosis factor-alpha (TNF
-[alpha]) in hemodynamic alterations, multiple organ damage, and
mortality caused by hemorrhagic shock, we employed a monoclonal
antibody to TNF-[alpha] (TNF-[alpha] MoAb) in anesthetized rats
subjected to prolonged hemorrhagic shock (mean arterial pressure: 30
-35 mm Hg for 180 min followed by resuscitation over 50 min).
Treatment with 20.0 mg/kg TNF-[alpha] MoAb 15 min after the end of
resuscitation significantly decreased the total peripheral resistance
index (p=0.031), in addition to providing remarkable protection from
multiple organ damage compared to controls. The 48 h survival rate
was significantly higher in the treatment group (73.3%) than in the
control group (26.7%; p=0.029). The results suggest that TNF-[alpha]
induced by hemorrhagic shock in rats is an important mediator for
pathophysiologic alterations associated with cardiovascular
abnormalities, multiple organ injury, and even lethality. Post
-resuscitation treatment with TNF-[alpha] MoAb, even after an initial
TNF-[alpha] formation has occurred, significantly attenuated the
cardiovascular consequences and improved the survival rate. Thus,
monoclonal antibodies to TNF-[alpha] might provide new prospects in
the treatment for hemorrhage related disorders.
Received 13 August 1996; accepted in final form 5 December 1996.
APS Manuscript Number H736-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996