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

Oded Szold*, Ron Ben-Abraham, Avi A. Weinbroum, Talma E. Englender, Dror Ovadia, Marc Sorkine, Cassian Bon, Ron Flaison, Patrick Sorkine

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Objectives: Tumor necrosis factor (TNF) has been reported as a mediator of local 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 envenomation-related hemodynamic depression and TNF antagonization (TNF antibodies or soluble TNF receptor). Design: A prospective, randomized, controlled experimental study using a rat 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. aspis 500 μg/kg was administered to the three experimental groups: venom only (group 1), venom and 40 μg anti-TNF antibodies (group 2), venom and 250 μg soluble TNF receptor (p55-R; group 3). Hemodynamic parameters were monitored up to 4 h following venom injection. Measurements and results: A significant hemodynamic deterioration (reduction in heart rate and blood pressure) occurred 30 min following venom injection in group 1 compared to groups 2 and 3, where hemodynamic parameters remained 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 pg/ml. Conclusions: The hemodynamic consequences of intramuscular injection of V. aspis venom can be blunted in a rat by systemic antagonization of TNF activity prior to venom injection. The poisonous hemodynamic effects of the V. aspis venom might be caused by systemic release of TNF.

Original languageEnglish
Pages (from-to)884-888
Number of pages5
JournalIntensive Care Medicine
Issue number5
StatePublished - 2001
Externally publishedYes


  • Metalloproteinases
  • Snake envenomation
  • TNF antibodies
  • Vipera aspis
  • p55-R


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