Patients with systemic inflammatory response syndrome (SIRS), or septic syndrome, often have cardiac dysfunction. The cellular and molecular mechanisms leading to myocardial dysfunction in these conditions remain unclear. Proinflammatory cytokines, particularly tumor necrosis factor-alpha (TNF-alpha), seem to be primary mediators of myocardial dysfunction in conditions of an exaggerated inflammatory response. Previous investigations in this laboratory have shown a decrease in the expression of connexin 43 (Cx43), a component of myocardial gap junctions, after administration of TNF. Myocardial gap junctions coordinate the synchronous contraction of the atrial and ventricles via the conduction of action potentials. Consequently, alterations in gap functional cellular communication may contribute to heart dysfuction during SIRS. The purpose of this investigation is to link disordered myocardial gap junctional cellular communication to the cardiac dysfunction seen in inflammatory states of elevated serum TNF. Moreover, the molecular mechanisms by which TNF causes decreased Cx43 expression will be characterized. A more exact understanding of the molecular events leading to myocardial dysfunction during inflammation may permit the development of specific therapeutic interventions to ameliorate this condition.
