title: Serum tumor necrosis factor-alpha does not mediate endotoxin-induced myocardial depression in rabbits.
abstract: Tumor necrosis factor-alpha (TNF-alpha) is an endogenous mediator for several effects of endotoxin. To evaluate whether TNF-alpha mediates endotoxin-induced left ventricular (LV) dysfunction, we measured LV function (sonomicrometers) and serum TNF-alpha (cytolytic assay) in anesthetized rabbits given endotoxin (100 micrograms/kg iv). In the control group (n = 8), systolic depression (defined by a > 10% increase in end-systolic volume at a matched end-systolic pressure) developed in four rabbits and diastolic dilation (> 10% increase in end-diastolic volume at a matched end-diastolic pressure) developed in three rabbits. Neither the increase in end-systolic volume nor the increase in end-diastolic volume correlated with the increase in TNF-alpha, which reached a peak of 2,875 +/- 762 U/ml. In a second group of rabbits (n = 7), a goat polyclonal anti-rabbit antibody to TNF-alpha was given 30-60 min before endotoxin. Anti-TNF-alpha antibody alone did not alter LV function. Although the TNF-alpha response to endotoxin was effectively blunted (peak TNF-alpha remained < 100 U/ml), all seven rabbits developed systolic depression (P = 0.08 compared with control group) and diastolic dilation (P = 0.03). We conclude that serum TNF-alpha does not mediate endotoxin-induced LV systolic depression or diastolic dilation in this model.
authors.affiliation: Department of Medicine, Department of Veterans Affairs Medical Center, San Diego, California, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: J
authors.initials: J
authors.lastname: Mathison
authors.forename: W Y
authors.initials: WY
authors.lastname: Lew
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001794:Blood Pressure; D001810:Blood Volume; D004731:Endotoxins / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D016277:Ventricular Function, Left
chemical_list: D000906:Antibodies; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha