Monoclonal Antibody to Tumor Necrosis Factor-alpha Attenuates Hemodynamic Dysfunction Secondary to Intestinal Ischemia/reperfusion in Rats

Objective: To evaluate the effects of monoclonal antibody to tumor necrosis factor (TNF)-alpha on the hemodynamic alterations and survival rate in rats subjected to intestinal ischemia/reperfusion.

Design: Prospective, randomized study.

Setting: Animal laboratory of an institute for research in traumatology.

Subjects: Male Sprague-Dawley rats, weighing 430 to 460 g.

Interventions: Anesthetized rats underwent 75 mins of superior mesenteric artery occlusion followed by 6 hrs of reperfusion. The animals were treated intravenously with either TNF-alpha monoclonal antibody (TN3, 20 mg/kg) or the control protein (albumin, 20 mg/kg) 30 mins before the onset of ischemia.

Measurements And Main Results: Pretreatment with TNF-alpha monoclonal antibody significantly attenuated the decreases in blood pressure and cardiac index (p < .01) compared with controls, for < or = 6 hrs after reperfusion. Stroke volume remained stable in the TNF-alpha monoclonal antibody-treated group and was significantly higher than in the control group at 0.5, 5, and 6 hrs after reperfusion (p < .05 at 0.5 and 5 hrs and p < .01 at 6 hrs). No differences in vascular resistance index values were observed between the two groups at any point in time (p > .05). After intestinal ischemia/reperfusion injury, both the portal and systemic TNF concentrations in the control animals were completely neutralized by TNF-alpha monoclonal antibody treatment. The 72-hr survival rate was significantly (p < .01) better in the treatment group (90%, 9/10) than in the control group (20%, 2/10).

Conclusions: These results suggest that intestinal ischemia/reperfusion injury can lead to increased TNF release into both the portal and the systemic circulation, which may be an important factor contributing to the development of hemodynamic dysfunction. Pretreatment with TNF-alpha monoclonal antibody significantly attenuates the cardiovascular consequences and improves the survival rate after acute intestinal ischemia/reperfusion injury.