Antagonization of TNF attenuates systemic hemodynamic manifestations of envenomation in a rat model of Vipera aspis snakebite

Objectives: Tumor necrosis factor (TNF) has been reported as a mediator of focal tissue injury following snake envenomation in an intact rat model. We investigated whether systemic release of TNF occurs following Vipera aspis envenomation, We further analyzed the possible connection between envenoma tion-related hemodynamic depression and TNF antagonization (TNF antibodies or soluble TNF receptor). Design: A prospective, randomized, controlled experimental study using a ra t model for snake envenomation. Settings: A medical university hospital research laboratory. Intervention: Eighty rats (300-400 g) were divided into four groups (n = 20 ): control and three experimental groups. Intramuscular injection of V. asi s 500 mug/kg was administered to the three experimental groups: venom only (group 1), venom and 40 mug anti-TNF antibodies (group 2), venom and 250 mu g soluble TNF receptor (p55-R; group 3). Hemodynamic parameters were monito red up to 4 h following venom injection. Measurements and results: A significant hemodynamic deterioration (reductio n in heart rate and blood pressure) occurred 30 min following venom injecti on in group 1 compared to groups 2 and 3, where hemodynamic parameters rema ined stable throughout the 4 h observation period. Serum levels of TNF were detected 15 min after venom injection and peaked after 2 h at 485 +/- 12 p g/ml. Conclusions: The hemodynamic consequences of intramuscular injection of V. aspis venom can be blunted in a rat by systemic antagonization of TNF activ ity prior to venom injection. The poisonous hemodynamic effects of the V. a spis venom might be caused by systemic release of TNF.