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 hem odynamic alterations, multiple organ damage, and mortality caused by h emorrhagic shock, we employed a monoclonal antibody to TNF-alpha (TNF- alpha MAb) in anesthetized rats subjected to prolonged hemorrhagic sho ck (mean arterial pressure of 30-35 mmHg for 180 min) followed by resu scitation over 50 min. Treatment of rats with 20.0 mg/kg TNF-alpha MAb 15 min after the end of resuscitation significantly decreased the tot al peripheral resistance index (P = 0.031) and provided remarkable pro tection from multiple organ damage compared with controls. The 48-h su rvival rate was significantly higher in the treatment group (73.3%) th an in the control group (26.7%; P = 0.029). The results suggest that T NF-alpha induced by hemorrhagic shock in rats is an important mediator of pathophysiological alterations associated with cardiovascular abno rmalities, multiple organ injury, and even lethality. Postresuscitatio n treatment with TNF-alpha MAb, even after an initial TNF-alpha format ion had occurred, significantly attenuated the cardiovascular conseque nces and improved the survival rate. Thus monoclonal antibodies to TNF -alpha might provide new prospects in the treatment of hemorrhage-rela ted disorders.