Tumor necrosis factor as a mediator of cardiac toxicity following snake envenomation

Oded Szold*, Ron Ben-Abraham, Inna Frolkis, Marc Sorkine, Patrick Sorkine

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Objective: To investigate the possible role of tumor necrosis factor in mediating cardiotoxicity following venom injection in a rat. Design: A randomized controlled experimental study using a Langendorff isolated heart model. Setting: Animal laboratory. Subjects: Adult male Wistar rats. Interventions: The control group (n = 10) was injected with saline only. Each animal in the experimental groups 1-3 (n = 10 each) was injected with Vipera aspis venom 500 μg/kg intramuscularly. Group 1 animals received no additional substance before-hand, group 2 animals were injected intramuscularly with 250 μg of soluble tumor necrosis factor receptor (sTNF-R p55) 15 mins before the venom injection, and group 3 animals were injected intraperitoneally with 40 μg of anti-tumor necrosis factor 60 mins before the venom injection. Measurements and Main Results: Cardiac performances were investigated following envenomation. Cardiac histology and myocardial tumor necrosis factor-RNA concentrations were assessed. Serum tumor necrosis factor concentrations rose and peaked 2 hrs following envenomation. A reduction in peak systolic pressures, maximum and minimum change in pressure over time, time-pressure integral, and coronary flow occurred in the venomonly-injected rats compared with controls, whereas blocking tumor necrosis factor activity prevented the deleterious cardiac effects of the envenomation. No histologic changes or increases in myocardial tumor necrosis factor-RNA concentrations were detected. Conclusion: These results strongly suggest that systemic release of tumor necrosis factor mediates cardiac toxicity following Vipera aspis envenomation.

Original languageEnglish
Pages (from-to)1449-1453
Number of pages5
JournalCritical Care Medicine
Issue number5
StatePublished - 1 May 2003


  • Metalloproteinases
  • Snake envenomation
  • Soluble tumor necrosis factor receptor p55
  • Tumor necrosis factor antibodies
  • Vipera aspis


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