Document Detail

Gene regulatory control of myocardial energy metabolism predicts postoperative cardiac function in patients undergoing off-pump coronary artery bypass graft surgery: inhalational versus intravenous anesthetics.
MedLine Citation:
PMID:  17325502     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Anesthetic gases modulate gene expression and provide organ protection. This study aimed at identifying myocardial transcriptional phenotypes to predict cardiovascular biomarkers and function in patients undergoing off-pump coronary artery bypass graft surgery. METHODS: In a prospective randomized trial, patients undergoing elective off-pump coronary artery bypass graft surgery were allocated to receive either the anesthetic gas sevoflurane (n = 10) or the intravenous anesthetic propofol (n = 10). Blood samples were collected perioperatively to determine cardiac troponin T, N-terminal pro-brain natriuretic peptide, and pregnancy-associated plasma protein A. Cardiac function was measured with transesophageal echocardiography and pulmonary artery thermodilution. Atrial biopsies were collected at the beginning and end of bypass surgery to determine gene expression profiles. RESULTS: N-terminal pro-brain natriuretic peptide and pregnancy-associated plasma protein A blood levels were decreased with sevoflurane treatment. Echocardiography showed preserved postoperative cardiac function in sevoflurane patients, which paralleled higher cardiac index measurements. N-terminal pro-brain natriuretic peptide release was predicted by sevoflurane-induced transcriptional reduction in fatty acid oxidation, whereas changes in cardiac index were predicted by preoperative gene activity of the peroxisome proliferator-activated receptor gamma coactivator-1alpha pathway. Sevoflurane-mediated attenuation of transcripts involved in DNA-damage signaling and activation of the granulocyte colony-stimulating factor survival pathway predicted improved postoperative cardiac index and diastolic heart function, respectively. CONCLUSIONS: Anesthetic-induced and constitutive gene regulatory control of myocardial substrate metabolism predicts postoperative cardiac function in patients undergoing off-pump coronary artery bypass graft surgery. The authors' analysis further points to novel cardiac survival pathways as potential therapeutic targets in perioperative cardioprotection.
Eliana Lucchinetti; Christoph Hofer; Lukas Bestmann; Martin Hersberger; Jianhua Feng; Min Zhu; Lukas Furrer; Marcus C Schaub; Reza Tavakoli; Michele Genoni; Andreas Zollinger; Michael Zaugg
Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  106     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-27     Completed Date:  2007-05-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  444-57     Citation Subset:  AIM; IM    
Institute of Anesthesiology, University Hospital Zurich, and Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
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MeSH Terms
Aged, 80 and over
Anesthetics, Inhalation / blood,  pharmacology*
Anesthetics, Intravenous / blood,  pharmacology*
Biological Markers / blood
Coronary Artery Bypass, Off-Pump / methods*
Echocardiography, Transesophageal / methods
Energy Metabolism / genetics*
Gene Expression Regulation* / drug effects
Heart Diseases / blood*,  prevention & control
Heart Function Tests / methods
Methyl Ethers / blood,  pharmacology
Middle Aged
Myocardium / metabolism*
Postoperative Complications / blood,  prevention & control
Predictive Value of Tests
Propofol / blood,  pharmacology
Prospective Studies
Thermodilution / methods
Reg. No./Substance:
0/Anesthetics, Inhalation; 0/Anesthetics, Intravenous; 0/Biological Markers; 0/Methyl Ethers; 2078-54-8/Propofol; 28523-86-6/sevoflurane
Comment In:
Anesthesiology. 2007 Mar;106(3):420-2   [PMID:  17325498 ]

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