Significance of TNF in hemorrhage-related hemodynamic alterations, organ injury, and mortality in rats.
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.
Bahrami
S
S
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria.
Yao
Y M
YM
Leichtfried
G
G
Redl
H
H
Marzi
I
I
Schlag
G
G
D000818:Animals; D004731:Endotoxins / Q000097:blood; D006439:Hemodynamics; D006470:Hemorrhage / Q000188:drug therapy* / Q000473:pathology; D007158:Immunologic Techniques; D007422:Intestines / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha