Hemorrhage activates myocardial NF kappa B and increases TNF-alpha in the heart

The heart is a tumor necrosis factor (TNF-alpha producing organ. Locally (<v systemically)-produced TNF alpha 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 TNF alpha following endotoxemia, it remains unknown whether shock, in the absence of sepsis, activates myocardial nuclear factor kappa B (NF kappa B, a TNF alpha transcription factor) and/or increases TNF alpha in the heart. To study this, rats were hemorrhaged and resuscitated, afterwhich hearts were harvested and analysed for evidence of NF kappa B activation (electrophoretic mobility shift assay) and assayed for TNF alpha levels. Hemorrhage and resuscitation activated NF kappa B and resulted in a dramatic increase in myocardial TNF alpha. This study constitutes the initial demonstration that hemorrhagic shock activates the signaling mechanisms which culminate in increased myocardial TNF alpha. 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. (C) 1997 Academic Press Limited.