Document Detail

Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion.
MedLine Citation:
PMID:  14693685     Owner:  NLM     Status:  MEDLINE    
Mitochondria play a critical role in myocardial cold ischemia-reperfusion (CIR) and induction of apoptosis. The nature and extent of mitochondrial defects and cytochrome c (Cyt c) release were determined by high-resolution respirometry in permeabilized myocardial fibers. CIR in a rat heart transplant model resulted in variable contractile performance, correlating with the decline of ADP-stimulated respiration. Respiration with succinate or N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (substrates for complexes II and IV) was partially restored by added Cyt c, indicating Cyt c release. In contrast, NADH-linked respiration (glutamate+malate) was not stimulated by Cyt c, owing to a specific defect of complex I. CIR but not cold ischemia alone resulted in the loss of NADH-linked respiratory capacity, uncoupling of oxidative phosphorylation and Cyt c release. Mitochondria depleted of Cyt c by controlled hypoosmotic shock provided a kinetic model of homogeneous Cyt c depletion. Comparison to Cyt c control of respiration in CIR-injured myocardial fibers indicated heterogeneity of Cyt c release. The complex I defect and uncoupling correlated with heterogeneous Cyt c release, the extent of which increased with loss of cardiac performance. These results demonstrate a complex pattern of multiple mitochondrial damage as determinants of CIR injury of the heart.
Andrey V Kuznetsov; Stefan Schneeberger; Rüdiger Seiler; Gerald Brandacher; Walter Mark; Wolfgang Steurer; Valdur Saks; Yves Usson; Raimund Margreiter; Erich Gnaiger
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Publication Detail:
Type:  In Vitro; Journal Article     Date:  2003-12-23
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  286     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-04-09     Completed Date:  2004-05-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1633-41     Citation Subset:  IM    
Department of Transplant Surgery, D. Swarovski Research Laboratory, University Hospital Innsbruck, A-6020 Innsbruck, Austria.
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MeSH Terms
Cytochromes c / metabolism*
Electron Transport Complex I / metabolism
Heart* / physiopathology
Mitochondria, Heart / metabolism*
Myocardial Contraction
Myocardial Ischemia / metabolism*,  physiopathology
Myocardial Reperfusion Injury / metabolism*,  physiopathology
Oxygen Consumption
Rats, Inbred Lew
Reg. No./Substance:
9007-43-6/Cytochromes c; EC Transport Complex I

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