Hemorrhage Activates Myocardial NFκB and Increases TNF-α in the Heart

The heart is a tumor necrosis factor (TNFα) producing organ. Locally (vsystemically)-produced TNFαlikely 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 TNFαfollowing endotoxemia, it remains unknown whether shock, in the absence of sepsis, activates myocardial nuclear factorκB (NFκB, a TNFαtranscription factor) and/or increases TNFαin the heart. To study this, rats were hemorrhaged and resuscitated, afterwhich hearts were harvested and analysed for evidence of NFκB activation (electrophoretic mobility shift assay) and assayed for TNFαlevels. Hemorrhage and resuscitation activated NFκB and resulted in a dramatic increase in myocardial TNFα. This study constitutes the initial demonstration that hemorrhagic shock activates the signaling mechanisms which culminate in increased myocardial TNFα. 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.