Sepsis-induced failure of hepatic energy metabolism.
OBJECTIVE
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.


METHODS
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.
Hart
David W
DW
Department of Surgery, The University of Texas Medical Branch, Galveston, Texas, USA. dcgore@utmb.edu
Gore
Dennis C
DC
Rinehart
Amanda J
AJ
Asimakis
Gregory K
GK
Chinkes
David L
DL
D000244:Adenosine Diphosphate / Q000032:analysis; D000249:Adenosine Monophosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D016470:Bacteremia / Q000378:metabolism; D001783:Blood Flow Velocity; D001794:Blood Pressure; D004734:Energy Metabolism; D006499:Hepatic Artery; D006503:Hepatic Veins; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D009243:NAD / Q000032:analysis / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D010766:Phosphorylation; D011169:Portal Vein; D011552:Pseudomonas Infections / Q000378:metabolism; D011550:Pseudomonas aeruginosa; D018805:Sepsis / Q000378:metabolism*; D012772:Shock, Septic / Q000378:metabolism / Q000382:microbiology; D013552:Swine
D009243:NAD; D019344:Lactic Acid; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D010100:Oxygen