Role Of Peroxynitrite In Sepsis-induced Cardiomyocytes Inflammatory Response

Objective The aim of this study is to determine the role of peroxynitrite(ONOO-) in sepsis-induced conversion of cardiomyocytes into a proinflammatory phenotype.Methods In vivo: Rat model of sepsis was induced by intraperitoneal(i.p.) injection of fecal material(180 mg/m L) at a dose of 3mg/g body weight. Rat received normal saline(NS) served as control(sham). Six hours after the induction of sepsis, rat plasma was isolated and hearts were harvested for myocardial myeloperoxidase(MPO) and neutrophil infiltration assay. In vitro:Rat cardiomyocytes challenged with plasma from septic rats used as in vitro model of sepsis.Cardiomyocyte ONOO-generation was determined by measuring nitrotyrosine(3-NT) with ELISA. Cardiomyocyte proinflammatory phenotype was determined by measuring chemokine(LIX and KC) expression with RT-PCR and ELISA; In addition, myocardial inflammation was determined with myocardial myeloperoxidase(MPO) and PMN accumulation.Results Rats with sepsis had increased myocardial MPO activity and PMN accumulation, and challenge of cardiomyocytes with septic plasma resulted in increase in cardiomyocyte ONOOgeneration and promoted cardiomyocytes conversion into a proinflammatory phenotype as indicated by increased LIX and KC expression. Pretreatment of the cardiomyocytes with ONOOdecomposition catalyst(Fe-TPPS) resulted in decreased myocardial MPO avtivity and PMN accumulation.The Fe-TPPS attenuated sepsis-induced cardiomyocyte ONOO-production and increased LIX and KC expression.Conclusions Our results indicate ONOO-generation plays an important role in conversion of cardiomyocytes into a proinflammatory phenotype in sepsis.