| Metabolic profiling of hearts exposed to sevoflurane and propofol reveals distinct regulation of fatty acid and glucose oxidation: CD36 and pyruvate dehydrogenase as key regulators in anesthetic-induced fuel shift. | |
| | |
MedLine Citation:
|
PMID: 20683255 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Myocardial energy metabolism is a strong predictor of postoperative cardiac function. This study profiled the metabolites and metabolic changes in the myocardium exposed to sevoflurane, propofol, and Intralipid and investigated the underlying molecular mechanisms. METHODS: Sevoflurane (2 vol%) and propofol (10 and 100 microM) in the formulation of 1% Diprivan (AstraZeneca Inc., Mississauga, ON, Canada) were compared for their effects on oxidative energy metabolism and contractility in the isolated working rat heart model. Intralipid served as a control. Substrate flux through the major pathways for adenosine triphosphate generation in the heart, that is, fatty acid and glucose oxidation, was measured using [H]palmitate and [C]glucose. Biochemical analyses of nucleotides, acyl-CoAs, ceramides, and 32 acylcarnitine species were used to profile individual metabolites. Lipid rafts were isolated and used for Western blotting of the plasma membrane transporters CD36 and glucose transporter 4. RESULTS: Metabolic profiling of the hearts exposed to sevoflurane and propofol revealed distinct regulation of fatty acid and glucose oxidation. Sevoflurane selectively decreased fatty acid oxidation, which was closely related to a marked reduction in left ventricular work. In contrast, propofol at 100 microM but not 10 microM increased glucose oxidation without affecting cardiac work. Sevoflurane decreased fatty acid transporter CD36 in lipid rafts/caveolae, whereas high propofol increased pyruvate dehydrogenase activity without affecting glucose transporter 4, providing mechanisms for the fuel shifts in energy metabolism. Propofol increased ceramide formation, and Intralipid increased hydroxy acylcarnitine species. CONCLUSIONS: Anesthetics and their solvents elicit distinct metabolic profiles in the myocardium, which may have clinical implications for the already jeopardized diseased heart. |
| | |
Authors:
|
Lianguo Wang; Kerry W S Ko; Eliana Lucchinetti; Liyan Zhang; Heinz Troxler; Martin Hersberger; Mohamed A Omar; Elena I Posse de Chaves; Gary D Lopaschuk; Alexander S Clanachan; Michael Zaugg |
Related Documents
:
|
8631955 - Glucuronic acid-conjugated dihydroxy fatty acids in the urine of patients with generali... 18026715 - R-alpha-lipoic acid and acetyl-l-carnitine complementarily promote mitochondrial biogen... 1764215 - Effects of high erucic acid rapeseed oil on fatty acid oxidation in rat liver. 10408755 - Fatty acid oxidation in the reperfused ischemic heart. 8302955 - Five new prenylated p-hydroxybenzoic acid derivatives with antimicrobial and molluscici... 964475 - High serum glutamic acid levels in patients with carcinoma of the pancreas. |
Publication Detail:
|
Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Anesthesiology Volume: 113 ISSN: 1528-1175 ISO Abbreviation: Anesthesiology Publication Date: 2010 Sep |
Date Detail:
|
Created Date: 2010-08-27 Completed Date: 2010-09-24 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: United States |
Other Details:
|
Languages: eng Pagination: 541-51 Citation Subset: AIM; IM |
Affiliation:
|
Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Anesthetics, Intravenous
/
pharmacology Animals Antigens, CD36 / metabolism* Energy Metabolism / drug effects, physiology Fatty Acids / metabolism* Glucose / metabolism* Heart / drug effects*, physiology Male Metabolome / drug effects, physiology Methyl Ethers / pharmacology* Myocardium / enzymology, metabolism* Oxidation-Reduction / drug effects Propofol / pharmacology* Pyruvate Dehydrogenase Complex / metabolism Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
|
0/Anesthetics, Intravenous; 0/Antigens, CD36; 0/Cd36 protein, rat; 0/Fatty Acids; 0/Methyl Ethers; 0/Pyruvate Dehydrogenase Complex; 2078-54-8/Propofol; 28523-86-6/sevoflurane; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: N-Acetylcysteine Protects against Bupivacaine-induced Myotoxicity Caused by Oxidative and Sarcoplasm...
Next Document: Images in Anesthesiology: Transient Paraplegia after Anesthesia for Magnetic Resonance Imaging.