CONICET | Buscador de Institutos y Recursos Humanos

MITOCHONDRIAL BIOENERGETICS IN THE ENDOTOXEMIC HEART V Vanasco, AP Carrivale, P Evelson, A Boveris, S Alvarez . Programa De Radicales Libres En Biología (PRALIB-CONICET), Facultad De Farmacia y Bioquímica, Universidad De Buenos Aires, Junín 956 C111AAD CABA, Argentina It has been observed inadequate tissue O2 consumption with normal pO2 in endotoxemia and sepsis. To describe the mechanism of bioenergetic failure occurring in heart mitochondria during this pathology, we analyzed the O2 consumption by tissue and mitochondria. Experimental endotoxemia was induced in female Sprague Dowley rats (45days) by LPS (10 mg/kg ip). Assays were performed in heart 6h after the treatment. The ratio between O2 consumed by mitochondria and by non-mitochondrial pathways decreased by 25% in LPS-animals compared to control animals. This observation may be due to a 2-fold increase in NADPH oxidase activity found in LPS-animals (control: 13 250 ± 3020cpm /mg tissue, p <0.05). Mitochondrial respiration was found decreased in LPS-animals (control: 159 ± 13 n-at g O2/min.mg prot, p<0,05). Increased rates of mitochondrial superoxide production (70%) and hydrogen peroxide (20%) in animals treated with LPS were also observed. Finally, ATP content and mitochondrial ATP production were found decreased in LPS animals. We suggest that a sustained and increased production of active oxygen species by mitochondria and a decreased ratio ATP production/O2 consumption, is a relevant bioenergetic mechanism contributing to tissue dysfunction in this pathology. This study was supported by: UBA, ANPCYT and CONICET.