Effects of Propofol on Cellular Bioenergetics in Human Skeletal Muscle Cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F18%3A43915988" target="_blank" >RIV/00216208:11120/18:43915988 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064173:_____/18:N0000025

Výsledek na webu

<a href="https://doi.org/10.1097/CCM.0000000000002875" target="_blank" >https://doi.org/10.1097/CCM.0000000000002875</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1097/CCM.0000000000002875" target="_blank" >10.1097/CCM.0000000000002875</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effects of Propofol on Cellular Bioenergetics in Human Skeletal Muscle Cells

Popis výsledku v původním jazyce

OBJECTIVES: Propofol may adversely affect the function of mitochondria and the clinical features of propofol infusion syndrome suggest that this may be linked to propofol-related bioenergetic failure. We aimed to assess the effect of therapeutic propofol concentrations on energy metabolism in human skeletal muscle cells. DESIGN: In vitro study on human skeletal muscle cells. SETTINGS: University research laboratories. SUBJECTS: Patients undergoing hip surgery and healthy volunteers. INTERVENTIONS: Vastus lateralis biopsies were processed to obtain cultured myotubes, which were exposed to a range of 1-10 μg/mL propofol for 96 hours. MEASUREMENTS AND MAIN RESULTS: Extracellular flux analysis was used to measure global mitochondrial functional indices, glycolysis, fatty acid oxidation, and the functional capacities of individual complexes of electron transfer chain. In addition, we used [1-C]palmitate to measure fatty acid oxidation and spectrophotometry to assess activities of individual electron transfer chain complexes II-IV. Although cell survival and basal oxygen consumption rate were only affected by 10 μg/mL of propofol, concentrations as low as 1 μg/mL reduced spare electron transfer chain capacity. Uncoupling effects of propofol were mild, and not dependent on concentration. There was no inhibition of any respiratory complexes with low dose propofol, but we found a profound inhibition of fatty acid oxidation. Addition of extra fatty acids into the media counteracted the propofol effects on electron transfer chain, suggesting inhibition of fatty acid oxidation as the causative mechanism of reduced spare electron transfer chain capacity. Whether these metabolic in vitro changes are observable in other organs and at the whole-body level remains to be investigated. CONCLUSIONS: Concentrations of propofol seen in plasma of sedated patients in ICU cause a significant inhibition of fatty acid oxidation in human skeletal muscle cells and reduce spare capacity of electron transfer chain in mitochondria.

Název v anglickém jazyce

Effects of Propofol on Cellular Bioenergetics in Human Skeletal Muscle Cells

Popis výsledku anglicky

OBJECTIVES: Propofol may adversely affect the function of mitochondria and the clinical features of propofol infusion syndrome suggest that this may be linked to propofol-related bioenergetic failure. We aimed to assess the effect of therapeutic propofol concentrations on energy metabolism in human skeletal muscle cells. DESIGN: In vitro study on human skeletal muscle cells. SETTINGS: University research laboratories. SUBJECTS: Patients undergoing hip surgery and healthy volunteers. INTERVENTIONS: Vastus lateralis biopsies were processed to obtain cultured myotubes, which were exposed to a range of 1-10 μg/mL propofol for 96 hours. MEASUREMENTS AND MAIN RESULTS: Extracellular flux analysis was used to measure global mitochondrial functional indices, glycolysis, fatty acid oxidation, and the functional capacities of individual complexes of electron transfer chain. In addition, we used [1-C]palmitate to measure fatty acid oxidation and spectrophotometry to assess activities of individual electron transfer chain complexes II-IV. Although cell survival and basal oxygen consumption rate were only affected by 10 μg/mL of propofol, concentrations as low as 1 μg/mL reduced spare electron transfer chain capacity. Uncoupling effects of propofol were mild, and not dependent on concentration. There was no inhibition of any respiratory complexes with low dose propofol, but we found a profound inhibition of fatty acid oxidation. Addition of extra fatty acids into the media counteracted the propofol effects on electron transfer chain, suggesting inhibition of fatty acid oxidation as the causative mechanism of reduced spare electron transfer chain capacity. Whether these metabolic in vitro changes are observable in other organs and at the whole-body level remains to be investigated. CONCLUSIONS: Concentrations of propofol seen in plasma of sedated patients in ICU cause a significant inhibition of fatty acid oxidation in human skeletal muscle cells and reduce spare capacity of electron transfer chain in mitochondria.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30221 - Critical care medicine and Emergency medicine

Projekt

<a href="/cs/project/NV16-28663A" target="_blank" >NV16-28663A: Funkční elektrickou stimulací asistovaná bicyklová ergometrie u kriticky nemocných: vztah mezi fyziologií svalu a dlouhodobým funkčním výsledkem léčby</a><br>

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Critical Care Medicine

ISSN

0090-3493

e-ISSN

—

Svazek periodika

46

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

"e206"-"e212"

Kód UT WoS článku

000426301500003

EID výsledku v databázi Scopus

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