| Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion. | |
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MedLine Citation:
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PMID: 14693685 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: In Vitro; Journal Article Date: 2003-12-23 |
Journal Detail:
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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:
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Created Date: 2004-04-09 Completed Date: 2004-05-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1633-41 Citation Subset: IM |
Affiliation:
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Department of Transplant Surgery, D. Swarovski Research Laboratory, University Hospital Innsbruck, A-6020 Innsbruck, Austria. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cryopreservation* Cytochromes c / metabolism* Electron Transport Complex I / metabolism Heart* / physiopathology Kinetics Male Mitochondria, Heart / metabolism* Myocardial Contraction Myocardial Ischemia / metabolism*, physiopathology Myocardial Reperfusion Injury / metabolism*, physiopathology Oxygen Consumption Rats Rats, Inbred Lew |
| Chemical | |
Reg. No./Substance:
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9007-43-6/Cytochromes c; EC 1.6.5.3/Electron Transport Complex I |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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