Background: Organ injury and dysfunction in sepsis accounts for significant morbidity and mortality. Adaptive cellular responses in the setting of sepsis prevent irreversible injury and allow for organ recovery. Others and we have shown that part of the adaptive response includes regulation of respiration and maintenance of a healthy mitochondrial population.Hypothesis: The purpose of these investigations were to test the hypothesis that regulation of mitochondrial respiration and homeostasis is regulated by inducible nitric oxide synthase (iNOS)/NO signaling. Furthermore, NO signaling is dependent on upregulation of heme oxygenase-1 (HO-1) and carbon monoxide (CO) signaling.Methods: Experimental sepsis was induced using a cecal ligation and puncture model in iNOS knockout (ko) or wild type (C57BL/6) mice. Some mice were randomized to treatment with CO-releasing molecule (CORM 10mg/kg), the NO …
