부산대학교 도서관

The present study investigated the effect of tumor necrosis factor (TNF)-[alpha] on myocardial energy metabolism as estimated by myocardial oxygen consumption ([MVo.sub.2]). [MVo.sub.2] of electrically stimulated isolated trabeculae of right ventricular Wistar rat myocardium was analyzed using a Clark-type oxygen probe. After the initial data collection in the absence of TNF-[alpha], measurements were repeated after TNF-[alpha] stimulation. In separate experiments, pretreatment with the nitric oxide (NO) synthase inhibitor [N.sup.G]-nitro-L-arginine methyl ester (L-NAME) or the ceramidase inhibitor n-oleoylethanolamine (NOE) was done to investigate NO/sphingosine-related effects. TNF-[alpha] impaired myocardial economy at increasing stimulation frequencies without altering baseline [MVo.sub.2]. Incubation with TNF-[alpha] in the presence of L-NAME further impaired myocardial economy. NOE preincubation abrogated the TNF-[alpha] effect on myocardial economy. Moreover, the negative inotropic effect of TNF-[alpha] was observed in NOE-pretreated but not L-NAME-pretreated muscle fibers. Exogenous sphingosine mimicked the TNF-[alpha] effect on mechanics and energetics. We conclude that TNF-[alpha] impairs the economy of chemomechanical energy transduction primarily through a sphingosine-mediated pathway. cytokines; nitric oxide; myocardial energy metabolism; tumor necrosis factor-[alpha]