The proinflammatory cytokines TNF-alpha and IL-1 beta impair economy of contraction in human myocardium

Considerable experimental evidence has accumulated over the past years that proinflammatory cytokines, especially TNF-alpha and IL-1beta, impair myocardial function in different animal species. On the other hand, several prospective clinical trials studying TNF-alpha antagonist in patients with chronic heart failure were not able to demonstrate a benefit. As there might be a relevant species-related discrepancy, we intended to prove our previous results demonstrating impaired myocardial economy after exogenous administration of recombinant TNF-alpha in rat myocardium. In the present study, both TNF-alpha and IL-1beta not only revealed an immediate negative inotropic effect but also increased specific oxygen demand in human right-atrial myocardium. Enhanced oxygen consumption was not caused by an elevated basal metabolism but an impaired economy of contraction. Our results suggest that proinflammatory cytokines have a considerable effect on myocardial mechano-energetic parameters in human myocardium as well.