| Reduced in vivo high-energy phosphates precede adriamycin-induced cardiac dysfunction. | |
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MedLine Citation:
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PMID: 20495142 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Adriamycin (ADR) is an established, life-saving antineoplastic agent, the use of which is often limited by cardiotoxicity. ADR-induced cardiomyopathy is often accompanied by depressed myocardial high-energy phosphate (HEP) metabolism. Impaired HEP metabolism has been suggested as a potential mechanism of ADR cardiomyopathy, in which case the bioenergetic decline should precede left ventricular (LV) dysfunction. We tested the hypothesis that murine cardiac energetics decrease before LV dysfunction following ADR (5 mg/kg ip, weekly, 5 injections) in the mouse. As a result, the mean myocardial phosphocreatine-to-ATP ratio (PCr/ATP) by spatially localized (31)P magnetic resonance spectroscopy decreased at 6 wk after first ADR injection (1.79 + or - 0.18 vs. 1.39 + or - 0.30, means + or - SD, control vs. ADR, respectively, P < 0.05) when indices of systolic and diastolic function by magnetic resonance imaging were unchanged from control values. At 8 wk, lower PCr/ATP was accompanied by a reduction in ejection fraction (67.3 + or - 3.9 vs. 55.9 + or - 4.2%, control vs. ADR, respectively, P < 0.002) and peak filling rate (0.56 + or - 0.12 vs. 0.30 + or - 0.13 microl/ms, control vs. ADR, respectively, P < 0.01). PCr/ATP correlated with peak filling rate and ejection fraction, suggesting a relationship between cardiac energetics and both LV systolic and diastolic dysfunction. In conclusion, myocardial in vivo HEP metabolism is impaired following ADR administration, occurring before systolic or diastolic abnormalities and in proportion to the extent of eventual contractile abnormalities. These observations are consistent with the hypothesis that impaired HEP metabolism contributes to ADR-induced myocardial dysfunction. |
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Authors:
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M Y Maslov; V P Chacko; G A Hirsch; A Akki; M K Leppo; C Steenbergen; R G Weiss |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-21 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 299 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-30 Completed Date: 2010-08-30 Revised Date: 2011-08-03 |
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: H332-7 Citation Subset: IM |
Affiliation:
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Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-6568, USA. mikhail.maslov@caritaschristi.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism* Animals Antibiotics, Antineoplastic* Disease Models, Animal Down-Regulation Doxorubicin* Energy Metabolism* Magnetic Resonance Imaging, Cine Magnetic Resonance Spectroscopy Male Mice Mice, Inbred C57BL Myocardial Contraction Myocardium / metabolism* Phosphocreatine / metabolism* Stroke Volume Time Factors Ventricular Dysfunction, Left / chemically induced, metabolism*, physiopathology Ventricular Function, Left* |
| Grant Support | |
ID/Acronym/Agency:
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HL-63030/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 23214-92-8/Doxorubicin; 56-65-5/Adenosine Triphosphate; 67-07-2/Phosphocreatine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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