Sepsis-induced failure of hepatic energy metabolism

David W. Hart, Dennis C. Gore, Amanda J. Rinehart, Gregory K. Asimakis, David L. Chinkes

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Hypothesis. Recent evidence suggests that sepsis may induce an uncoupling of oxidative phosphorylation. The purpose of this study was to quantify temporal changes in hepatic oxygen consumption and cellular energy state with increasing severity of sepsis and thus assess the interrelationship of these parameters as either primary defect or compensatory response. Main outcome measures. Pseudomonas aeruginosa was infused intravenously in eight instrumented anesthetized swine inducing a progressive severity of sepsis to shock. Eight other animals served as instrumented controls. Hepatic blood flow, oxygen use, and concentrations of ATP, ADP, AMP, NAD+, and NADH were measured at baseline and then sequentially during the study. Results. Except for an increase in heart rate, there were no temporal changes in measured values for the control animals. For swine receiving P. aeruginosa, hepatic oxygen delivery and consumption increased with early sepsis whereas there were no alterations in the concentrations of adenine nucleotides or NAD +/NADH within liver. Septic shock was notable for a decrease in oxygen delivery yet oxygen consumption remained elevated because of an increase in percent oxygen extraction. The hepatic concentrations of ATP and NADH decreased during septic shock. Conclusions. These findings suggest that any sepsis-induced limitation in phosphorylation may be initially compensated by an increase in oxygen use. This study also suggests that decreases in NADH availability may be a principal factor in the decompensation of sepsis to shock.

Original languageEnglish (US)
Pages (from-to)139-147
Number of pages9
JournalJournal of Surgical Research
Volume115
Issue number1
DOIs
StatePublished - Nov 2003

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Keywords

  • ATP
  • Hepatic blood flow
  • Lactic acid
  • NAD/NADH
  • Oxygen use

ASJC Scopus subject areas

  • Surgery

Cite this

Hart, D. W., Gore, D. C., Rinehart, A. J., Asimakis, G. K., & Chinkes, D. L. (2003). Sepsis-induced failure of hepatic energy metabolism. Journal of Surgical Research, 115(1), 139-147. https://doi.org/10.1016/S0022-4804(03)00284-1