Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Myocardial dysfunction is a known manifestation of this syndrome, although the mechanisms of how systemic inflammation could affect it remain still unknown. The magnitude of the inflammatory response is vital for
resolving sepsis. The aim of this work was to elucidate the relationship between the severity of the systemic inflammatory response with cardiac mitochondrial function, and its impact on cardiac function. Female Sprague-Dawley rats received i.p. injection of LPS 0.5 mg/kg or LPS 8 mg/kg body wt or vehicle. After 6 h of treatment, NO and ROS production in blood cells were measured, pro-inflammatory cytokines levels were assessed in plasma and heart tissue, heart mitochondrial function was measured, and ventricular contractile reserve and lusitropic reserve were evaluated. NO levels in bloodstream were assessed by NO-Hb adduct by EPR; and nitrates/nitrites levels and NO increased by 5-fold in LPS 0.5 and by 11- fold in LPS 8. These results are accompanied by the increase in TNF-α and IL-6 levels in plasma. Also, polymorphonuclear cells (PMN) activation was evaluated by
flow citometry. NO production in PMN increased by 42% and 60% in LPS 0.5 and LPS 8, while ROS production in PMN increased by 88% in LPS 0.5 and by 94% in LPS 8, respectively. LPS treatment induced mitochondrial dysfunction in the highest dose: ATP production decreased by 30%, mitochondrial membrane potential decrease by 18% as well as complex I activity. Mitochondrial H2O2 production increased by 40% and 59% in LPS 0.5 and LPS 8 doses (control: 0.128 ± 0.013 nmol/min-mg prot, p<0.05). TNF-α and IL1-β mRNA expression were increased in heart tissue in both LPS groups. Cardiac function was observed altered in LPS treatment. Interestingly, impaired contractile reserve and lusitropic reserve were observed in response to a β-adrenergic stimulus with isoproterenol in LPS 0.5 and LPS 8 treated animals, although mitochondrial function was conserved in LPS 0.5 group. These results evidence that mitochondrial dysfunction is related to the severity of the inflammation response, although may not be the only pathway involved in cardiac diastolic and systolic dysfunction. It is worth to consider the importance of restoring cardiac mitochondrial function to prevent heart failure in sepsis, and to improve patients´outcome.