Document Detail

Isoflurane Protects the Myocardium Against Ischemic Injury via the Preservation of Mitochondrial Respiration and Its Supramolecular Organization.
MedLine Citation:
PMID:  25383718     Owner:  NLM     Status:  Publisher    
BACKGROUND:: Isoflurane has been demonstrated to limit myocardial ischemic injury. This effect is hypothesized to be mediated in part via effects on mitochondria. We investigated the hypothesis that isoflurane maintains mitochondrial respiratory chain functionality, in turn limiting mitochondrial damage and mitochondrial membrane disintegration during myocardial ischemic injury.
METHODS:: Mice (9-12 weeks of age) received isoflurane (1.0 minimum alveolar concentration) 36 hours before a 30-minute coronary artery occlusion that was followed by 24 hours of reperfusion. Cardiac mitochondria were isolated at a time point corresponding to 4 hours of reperfusion. 2,3,5-Triphenyltetrazoliumchloride staining was used to determine myocardial infarct size. Mitochondrial respiratory chain functionality was investigated using blue native polyacrylamide gel electrophoresis, as well as specific biochemical assays. Mitochondrial lipid peroxidation was quantified via the formation of malondialdehyde; mitochondrial membrane integrity was assessed by Ca-induced swelling. Protein identification was achieved via liquid chromatography mass spectrometry/mass spectrometry.
RESULTS:: Thirty-one mice were studied. Mice receiving isoflurane displayed a reduced myocardial infarct size (P = 0.0011 versus ischemia/reperfusion [I/R]), accompanied by a preserved activity of respiratory complex III (P = 0.0008 versus I/R). Isoflurane stabilized mitochondrial supercomplexes consisting of oligomers from complex III/IV (P = 0.0086 vs I/R). Alleviation of mitochondrial damage after isoflurane treatment was further demonstrated as decreased malondialdehyde formation (P = 0.0019 versus I/R) as well as a diminished susceptibility to Ca-induced swelling (P = 0.0010 versus I/R).
CONCLUSIONS:: Our findings support the hypothesis that isoflurane protects the heart from ischemic injury by maintaining the in vivo functionality of the mitochondrial respiratory chain. These effects may result in part from the preservation of mitochondrial supramolecular organization and minimized oxidative damage, circumventing the loss of mitochondrial membrane integrity.
Christopher Lotz; Jun Zhang; Caiyun Fang; David Liem; Peipei Ping
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-7
Journal Detail:
Title:  Anesthesia and analgesia     Volume:  -     ISSN:  1526-7598     ISO Abbreviation:  Anesth. Analg.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-10     Completed Date:  -     Revised Date:  2014-11-11    
Medline Journal Info:
Nlm Unique ID:  1310650     Medline TA:  Anesth Analg     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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