ObjectiveTo investigate the possible role of tumor necrosis factor in mediating cardiotoxicity following venom injection in a rat.DesignA randomized controlled experimental study using a Langendorff isolated heart model.SettingAnimal laboratory.SubjectsAdult male Wistar rats.InterventionsThe control group (n = 10) was injected with saline only. Each animal in the experimental groups 1–3 (n = 10 each) was injected withVipera aspisvenom 500 &mgr;g/kg intramuscularly. Group 1 animals received no additional substance beforehand, group 2 animals were injected intramuscularly with 250 &mgr;g of soluble tumor necrosis factor receptor (sTNF-R p55) 15 mins before the venom injection, and group 3 animals were injected intraperitoneally with 40 &mgr;g of anti-tumor necrosis factor 60 mins before the venom injection.Measurements and Main ResultsCardiac 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 venom-only-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.ConclusionThese results strongly suggest that systemic release of tumor necrosis factor mediates cardiac toxicity followingVipera aspisenvenomation.