title: Recombinant human tumor necrosis factor produces hemodynamic changes characteristic of sepsis and endotoxemia.
abstract: Tumor necrosis factor (TNF) is a macrophage-derived peptide mediator released during endotoxemia and sepsis. We examined the systemic and visceral hemodynamic response to low doses of human recombinant TNF in rats. Each animal received a 30-minute intravenous infusion of either saline solution (n = 8) or TNF (n = 8) in a dose of 0.25 mg/kg or 1.0 mg/kg. Thermodilution cardiac output, blood pressure, pulse, vascular resistance, effective hepatic blood flow (galactose clearance), and effective renal plasma flow (p-aminohippurate clearance) were determined at time = 2 hours. The 0.25-mg/kg dose had no apparent effect on systemic hemodynamics. The 1.0-mg/kg dose produced a hyperdynamic systemic circulatory response with an elevated cardiac output, tachycardia, and a diminished systemic vascular resistance. Effective hepatic blood flow was exquisitely sensitive to even the lowest dose of TNF, with a 29% reduction despite the normal cardiac output. Renal flow was unaffected by either dose. Tumor necrosis factor-induced systemic and visceral hemodynamic changes are remarkably similar to those seen in gram-negative sepsis, suggesting that TNF may occupy a proximal position in the pathogenesis of overwhelming infection.
authors.affiliation: Department of Surgery, Veterans Administration Medical Center, Cleveland, OH 44106.
authors.forename: W J
authors.initials: WJ
authors.lastname: Schirmer
authors.forename: J M
authors.initials: JM
authors.lastname: Schirmer
authors.forename: D E
authors.initials: DE
authors.lastname: Fry
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004731:Endotoxins / Q000097:blood*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008102:Liver Circulation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D004731:Endotoxins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha