Evaluation of the effect of sepsis on intermediate metabolism on heart and skeletal muscle using carbon(13) NMR spectroscopy.

摘要

Sepsis is the systemic response of the body to the severe infection characterized by the presence of bacteria in the circulation bloodstream. It is now the leading cause of death in the surgical intensive care unit. Sepsis has been demonstrated as an acquired disease of intermediary metabolism. Alterations in metabolism have been suggested as playing an important role in the development and outcome of the clinical complications of sepsis. However, the cellular mechanisms responsible for the consequence of sepsis have not been fully elucidated.; The purpose of this investigation was to examine the effect of sepsis on intermediary and/or mitochondrial metabolism. Specifically, the etiology of increased blood lactate concentration, TCA cycle metabolism, pyruvate dehydrogenase activity and substrate utilization during sepsis were investigated. {dollar}sp{lcub}13{rcub}{dollar}C NMR spectroscopy in concert with isolated perfused organ techniques were employed to address these issues. Isotopomer analysis developed by Malloy was used to derive the TCA cycle flux via acetyl CoA and the contribution of anapleurotic pathways to TCA cycle flux. Hindlimb and heart from the septic rat model were examined.; No evidence was found that sepsis impaired mitochondrial oxidative function. Results from perfused hindlimb demonstrate high anapleurotic activity relative to TCA cycle flux in both fasted-sham and septic rats. Potential sources for the commonly observed increased blood lactate in sepsis are increased glycolysis and anapleurotic pathways. No impairment of PDH activity was observed in the isolated perfused rat heart. Myocardial endogenous amino acid and lactate utilization increases while free fatty acid oxidation decreases.