Sepsis-induced failure of hepatic energy metabolism

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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

Fingerprint

Liver Failure
NAD
Energy Metabolism
Sepsis
Oxygen Consumption
Liver
Oxygen
Septic Shock
Pseudomonas aeruginosa
Shock
Swine
Adenosine Triphosphate
Adenine Nucleotides
Oxidative Phosphorylation
Adenosine Monophosphate
Adenosine Diphosphate
Heart Rate
Phosphorylation
Outcome Assessment (Health Care)

Keywords

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

ASJC Scopus subject areas

  • Surgery

Cite this

Hart, D. W., Gore, D., 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

Sepsis-induced failure of hepatic energy metabolism. / Hart, David W.; Gore, Dennis; Rinehart, Amanda J.; Asimakis, Gregory K.; Chinkes, David L.

In: Journal of Surgical Research, Vol. 115, No. 1, 11.2003, p. 139-147.

Research output: Contribution to journalArticle

Hart, DW, Gore, D, Rinehart, AJ, Asimakis, GK & Chinkes, DL 2003, 'Sepsis-induced failure of hepatic energy metabolism', Journal of Surgical Research, vol. 115, no. 1, pp. 139-147. https://doi.org/10.1016/S0022-4804(03)00284-1
Hart, David W. ; Gore, Dennis ; Rinehart, Amanda J. ; Asimakis, Gregory K. ; Chinkes, David L. / Sepsis-induced failure of hepatic energy metabolism. In: Journal of Surgical Research. 2003 ; Vol. 115, No. 1. pp. 139-147.
@article{ddc2ba618bec420b801ad32f28f44d7e,
title = "Sepsis-induced failure of hepatic energy metabolism",
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.",
keywords = "ATP, Hepatic blood flow, Lactic acid, NAD/NADH, Oxygen use",
author = "Hart, {David W.} and Dennis Gore and Rinehart, {Amanda J.} and Asimakis, {Gregory K.} and Chinkes, {David L.}",
year = "2003",
month = "11",
doi = "10.1016/S0022-4804(03)00284-1",
language = "English (US)",
volume = "115",
pages = "139--147",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Sepsis-induced failure of hepatic energy metabolism

AU - Hart, David W.

AU - Gore, Dennis

AU - Rinehart, Amanda J.

AU - Asimakis, Gregory K.

AU - Chinkes, David L.

PY - 2003/11

Y1 - 2003/11

N2 - 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.

AB - 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.

KW - ATP

KW - Hepatic blood flow

KW - Lactic acid

KW - NAD/NADH

KW - Oxygen use

UR - http://www.scopus.com/inward/record.url?scp=0142218019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0142218019&partnerID=8YFLogxK

U2 - 10.1016/S0022-4804(03)00284-1

DO - 10.1016/S0022-4804(03)00284-1

M3 - Article

C2 - 14572785

AN - SCOPUS:0142218019

VL - 115

SP - 139

EP - 147

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 1

ER -