Journal of Endotoxin Research

 

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Journal of Endotoxin Research, Vol. 12, No. 6, 358-366 (2006)
DOI: 10.1177/09680519060120060601
© 2006 SAGE Publications

Effect of endotoxin, dobutamine and dopamine on muscle mitochondrial respiration in vitro

Francesca Porta

Department of Intensive Care Medicine, University Hospital Bern, Bern, Switzerland

Jukka Takala

Department of Intensive Care Medicine, University Hospital Bern, Bern, Switzerland

Christian Weikert

Department of Intensive Care Medicine, University Hospital Bern, Bern, Switzerland

Priska Kaufmann

Department of Clinical Pharmacology & Toxicology and Department of Research, University Hospital, Basel, Switzerland

Stephan Krahenbuhl

Department of Clinical Pharmacology & Toxicology and Department of Research, University Hospital, Basel, Switzerland, stephan.jakob{at}insel.ch

Stephan M. Jakob

Department of Intensive Care Medicine, University Hospital Bern, Bern, Switzerland

Introduction: Mitochondrial respiration is impaired during endotoxemia. While catecholamines are frequently used in sepsis, their effects on mitochondrial function are controversial. We assessed effects of dobutamine and dopamine endotoxin on isolated muscle mitochondria.

Materials and Methods : Sternocleidomastoid muscle mitochondria were isolated from six anesthetized pigs. Each sample was divided into six different groups. Three groups were incubated with endotoxin, three with vehicle. After 1 h, dopamine and dobutamine at final concentrations of 100 µM were added to the vehicle and endotoxin groups. After 2 h, state 3 and 4 respiration rates were determined for all mitochondrial complexes. Oxygen consumption was determined with a Clark-type electrode.

Results: Endotoxin increased glutamate-dependent state 4 respiration from 9.3 ± 3.6 to 31.9 ± 9.1 (P = 0.001) without affecting state 3 respiration. This reduced the efficiency of mitochondrial respiration (RCR; state 3/state 4, 9.9 ± 1.9 versus 3.6 ± 0.6; P < 0.001). The other complexes were unaffected. Catecholamine partially restored the endotoxin-induced increase in complex I state 4 respiration rate (31.9 ± 9.1 versus 17.1 ± 6.4 and 20.1 ± 12.2) after dopamine and dobutamine, respectively (P = 0.007), and enhanced the ADP:O ratio (P = 0.033).

Conclusions: Dopamine and dobutamine enhanced the efficiency of mitochondrial respiration after short-term endotoxin exposure.

Key Words: Dobutamine • dopamine • endotoxin • mitochondria • muscle


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