Title
Possible pathogenic mechanism of propofol infusion syndrome involves coenzyme Q
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Philadelphia, Pa ,
Subject
Human medicine
Source (journal)
Anesthesiology / American Society of Anesthesiologists. - Philadelphia, Pa, 1940, currens
Volume/pages
122(2015) :2 , p. 343-352
ISSN
0003-3022
ISI
000351734900014
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Background: Propofol is a short-acting intravenous anesthetic agent. In rare conditions, a life-threatening complication known as propofol infusion syndrome can occur. The pathophysiologic mechanism is still unknown. Some studies suggested that propofol acts as uncoupling agent, others suggested that it inhibits complex I or complex IV, or causes increased oxidation of cytochrome c and cytochrome aa(3), or inhibits mitochondrial fatty acid metabolism. Although the exact site of interaction is not known, most hypotheses point to the direction of the mitochondria. Methods: Eight rats were ventilated and sedated with propofol up to 20 h. Sequential biopsy specimens were taken from liver and skeletal muscle and used for determination of respiratory chain activities and propofol concentration. Activities were also measured in skeletal muscle from a patient who died of propofol infusion syndrome. Results: In rats, authors detected a decrease in complex II+III activity starting at low tissue concentration of propofol (20 to 25 mu M), further declining at higher concentrations. Before starting anesthesia, the complex II+III/citrate synthase activity ratio in liver was 0.46 (0.25) and in skeletal muscle 0.23 (0.05) (mean [SD]). After 20 h of anesthesia, the ratios declined to 0.17 (0.03) and 0.12 (0.02), respectively. When measured individually, the activities of complexes II and III remained normal. Skeletal muscle from one patient taken in the acute phase of propofol infusion syndrome also shows a selective decrease in complex II+III activity (z-score: -2.96). Conclusion: Propofol impedes the electron flow through the respiratory chain and coenzyme Q is the main site of interaction with propofol.
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