Effects of prolonged endotoxemia on liver, skeletal muscle and kidney mitochondrial function.
BACKGROUND
Sepsis may impair mitochondrial utilization of oxygen. Since hepatic dysfunction is a hallmark of sepsis, we hypothesized that the liver is more susceptible to mitochondrial dysfunction than the peripheral tissues, such as the skeletal muscle. We studied the effect of prolonged endotoxin infusion on liver, muscle and kidney mitochondrial respiration and on hepatosplanchnic oxygen transport and microcirculation in pigs.


METHODS
20 anesthetized pigs were randomized to receive endotoxin or saline infusion for 24 hours. Muscle, liver and kidney mitochondrial respiration was assessed. Cardiac output (thermodilution), carotid, superior mesenteric and kidney arterial, portal venous (ultrasound Doppler) and microcirculatory blood flow (laser Doppler) were measured, and systemic and regional oxygen transport and lactate exchange were calculated.


RESULTS
Endotoxin infusion induced hyperdynamic shock and impaired the glutamate- and succinate-dependent mitochondrial respiratory control ratio (RCR) in the liver (glutamate: endotoxemia: median [range] 2.8 [2.3-3.8] vs. controls: 5.3 [3.8-7.0]; p<0.001; succinate: endotoxemia: 2.9 [1.9-4.3] vs. controls: 3.9 [2.6-6.3] p=0.003). While the ADP:O ratio was reduced with both substrates, maximal ATP production was impaired only in the succinate-dependent respiration. Hepatic oxygen consumption and extraction, and liver surface laser Doppler blood flow remained unchanged. Glutamate-dependent respiration in the muscle and kidney was unaffected.


CONCLUSIONS
Endotoxemia reduces the efficiency of hepatic but neither skeletal muscle nor kidney mitochondrial respiration, independent of regional and microcirculatory blood flow changes.
Porta
Francesca
F
Department of Intensive Care Medicine, University Hospital Bern, CH-3010 Bern, Switzerland. francesca.porta@dkf.unibe.ch
Takala
Jukka
J
Weikert
Christian
C
Bracht
Hendrik
H
Kolarova
Anna
A
Lauterburg
Bernhard H
BH
Borotto
Erika
E
Jakob
Stephan M
SM
D000818:Animals; D019069:Cell Respiration / Q000502:physiology; D019446:Endotoxemia / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D013552:Swine; D013997:Time Factors