Effects of prolonged endotoxemia on liver, skeletal muscle and kidney mitochondrial function

Porta, Francesca; Takala, Jukka; Weikert, Christian; Bracht, Hendrik; Kolarova, Anna; Lauterburg, Bernhard H; Borotto, Erika; Jakob, Stephan M (2006). Effects of prolonged endotoxemia on liver, skeletal muscle and kidney mitochondrial function. Critical care, 10(4), R118. London: BioMed Central 10.1186/cc5013

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INTRODUCTION: 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care
04 Faculty of Medicine > Service Sector > Institute of Clinical Pharmacology and Visceral Research (discontinued)

UniBE Contributor:

Takala, Jukka; Lauterburg, Bernhard and Jakob, Stephan

ISSN:

1364-8535

ISBN:

16895596

Publisher:

BioMed Central

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:45

Last Modified:

10 Oct 2019 16:46

Publisher DOI:

10.1186/cc5013

PubMed ID:

16895596

Web of Science ID:

000247712300021

BORIS DOI:

10.7892/boris.18548

URI:

https://boris.unibe.ch/id/eprint/18548 (FactScience: 740)

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