title: Tumor necrosis factor as a mediator of cardiac toxicity following snake envenomation.
abstract: OBJECTIVE
  To investigate the possible role of tumor necrosis factor in mediating cardiotoxicity following venom injection in a rat.
  
  
  METHODS
  A randomized controlled experimental study using a Langendorff isolated heart model.
  
  
  METHODS
  Animal laboratory.
  
  
  METHODS
  Adult male Wistar rats.
  
  
  METHODS
  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 microg/kg intramuscularly. Group 1 animals received no additional substance beforehand, group 2 animals were injected intramuscularly with 250 microg of soluble tumor necrosis factor receptor (sTNF-R p55) 15 mins before the venom injection, and group 3 animals were injected intraperitoneally with 40 microg of anti-tumor necrosis factor 60 mins before the venom injection.
  
  
  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 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.
  
  
  CONCLUSIONS
  These results strongly suggest that systemic release of tumor necrosis factor mediates cardiac toxicity following Vipera aspis envenomation.
authors.affiliation: General Intensive Care Unit, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Szold
authors.forename: Ron
authors.initials: R
authors.lastname: Ben-Abraham
authors.forename: Inna
authors.initials: I
authors.lastname: Frolkis
authors.forename: Marc
authors.initials: M
authors.lastname: Sorkine
authors.forename: Patrick
authors.initials: P
authors.lastname: Sorkine
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006331:Heart Diseases / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009206:Myocardium / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000627:therapeutic use; D047888:Receptors, Tumor Necrosis Factor, Type I; D012909:Snake Bites / Q000097:blood / Q000150:complications* / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017819:Viperidae
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D012313:RNA