Unravelling the relationship between the severity of endotoxemia with mitochondria dysfunction: impact in cardiac function

MARCHINI T; CALABRÓ V; FERRERO M; CORACH D; GELPI R; VICO T; LORENZETTI M; GARCES M; GONZALEZ MAGLIO D; MAZO T; EVELSON P; VANASCO V; ADAN AREAN JS; VALDÉZ L; GINART S; D´ANNUNZIO V; ALVAREZ S

Lisboa

Congreso; SFRRI Lisboa 2018 (hosted by SFRR-E); 2018

Society for Free Radical Research International

The aim of this work was to elucidate the relationship between theseverity of the systemic inflammation response with cardiac dysfunctionand mitochondrial function in endotoxemia and sepsis. Female Sprague-Dawley rats were i.p. injected with LPS (0.5 mg/kg or 8 mg/kg body wt) orvehicle, and after 6 h were euthanized. Blood NO-Hb adduct levels in-creased by 5-fold after LPS 0.5, and 11-fold after LPS 8. NO production byPMN increased by 42% in LPS 0.5, and 60% in LPS 8 group, while ROS production increased by 90% in both treatments. Impaired cardiac con-tractile reserve and lusitropic reserve were observed in both LPS groups.However, systemic and local inflammation was only observed after LPS 8.Finally, mitochondrial H2O2 production increased by 40% and 60% in LPS0.5 and LPS 8 groups (control: 0.128 7 0.013 nmol/min-mg prot, p menor 0.05). However, mitochondrial membrane potential and ATP production only decreased after LPS 8 by 18% and 30%, respectively. These resultsevidence that mitochondrial dysfunction is related to the severity of theinflammation response, although may not be the only pathway involvedin cardiac diastolic and systolic dysfunction. Restoring systemic oxidative stress and cardiac mitochondrial function could be a strategy to overcome heart failure in sepsis.