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

VICO TAMARA; LORENZETTI MARIO; MARCHINI TIMOTEO; ADAN AREAN JUAN SANTIAGO; CALABRÓ VALERIA; MARIANA GARCES; VALDEZ LAURA; FERRERO MARIANA; GONZALEZ MAGLIO DANIEL; CORACH DANIEL; MAZO TAMARA; DANNUNZIO VERONICA; GELPI RICARDO; VANASCO VIRGINIA; EVELSON PABLO; ALVAREZ, SILVIA

Congreso; 18th Biennial Meeting of the SFRRI; 2018

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 SpragueDawley 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 increased 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 ROSproduction increased by 90% in both treatments. Impaired cardiac contractile 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,po0.05). 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 stress oxidative and cardiac mitochondrial function could be a strategy toovercome heart failure in sepsis.