title: Hemorrhage activates myocardial NFkappaB and increases TNF-alpha in the heart.
abstract: The heart is a tumor necrosis factor (TNFalpha) producing organ. Locally (v systemically)-produced TNFalpha likely contributes to myocardial dysfunction via direct suppression of myocardial contractile function, the induction of myocardial apoptosis, and the genesis of cardiac hypertrophy. Although recent studies have demonstrated increased myocardial TNFalpha following endotoxemia, it remains unknown whether shock, in the absence of sepsis, activates myocardial nuclear factor kappa B (NFkappaB, a TNFalpha transcription factor) and/or increases TNFalpha in the heart. To study this, rats were hemorrhaged and resuscitated, after which hearts were harvested and analysed for evidence of NFkappaB activation (electrophoretic mobility shift assay) and assayed for TNFalpha levels. Hemorrhage and resuscitation activated NFkappaB and resulted in a dramatic increase in myocardial TNFalpha. This study constitutes the initial demonstration that hemorrhagic shock activates the signaling mechanisms which culminate in increased myocardial TNFalpha. Indeed, this may have important clinical implications, since hemorrhage is a frequent complication of both iatrogenic and accidental trauma, as well as a potent instigator of multiple organ failure.
authors.affiliation: Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Meldrum
authors.forename: R
authors.initials: R
authors.lastname: Shenkar
authors.forename: B C
authors.initials: BC
authors.lastname: Sheridan
authors.forename: B S
authors.initials: BS
authors.lastname: Cain
authors.forename: E
authors.initials: E
authors.lastname: Abraham
authors.forename: A H
authors.initials: AH
authors.lastname: Harken
mesh_terms: D000818:Animals; D006321:Heart; D006470:Hemorrhage / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha