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Am J Physiol Heart Circ Physiol 272: H2219-H2226, 1997;
0363-6135/97 $5.00
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AJP - Heart and Circulatory Physiology, Vol 272, Issue 5 2219-H2226, Copyright © 1997 by American Physiological Society

ARTICLES

Significance of TNF in hemorrhage-related hemodynamic alterations, organ injury, and mortality in rats

S. Bahrami, Y. M. Yao, G. Leichtfried, H. Redl, I. Marzi and G. Schlag
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.

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 MAb) in anesthetized rats subjected to prolonged hemorrhagic shock (mean arterial pressure of 30-35 mmHg for 180 min) followed by resuscitation over 50 min. Treatment of rats with 20.0 mg/kg TNF-alpha MAb 15 min after the end of resuscitation significantly decreased the total peripheral resistance index (P = 0.031) and provided remarkable protection from multiple organ damage compared with 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 of pathophysiological alterations associated with cardiovascular abnormalities, multiple organ injury, and even lethality. Postresuscitation treatment with TNF-alpha MAb, even after an initial TNF-alpha formation had occurred, significantly attenuated the cardiovascular consequences and improved the survival rate. Thus monoclonal antibodies to TNF-alpha might provide new prospects in the treatment of hemorrhage-related disorders.


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