| Role of MgADP in the development of diastolic dysfunction in the intact beating rat heart. | |
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MedLine Citation:
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PMID: 9045879 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sarcomere relaxation depends on dissociation of actin and myosin, which is regulated by a number of factors, including intracellular [MgATP] as well as MgATP hydrolysis products [MgADP] and inorganic phosphate [Pi], pHi, and cytosolic calcium concentration ([Ca2+]c). To distinguish the contribution of MgADP from the other regulators in the development of diastolic dysfunction, we used a strategy to increase free [MgADP] without changing [MgATP], [Pi], or pHi. This was achieved by applying a low dose of iodoacetamide to selectively inhibit the creatine kinase activity in isolated perfused rat hearts. [MgATP], [MgADP], [Pi], and [H+] were determined using 31P NMR spectroscopy. The [Ca2+]c and the glycolytic rate were also measured. We observed an approximately threefold increase in left ventricular end diastolic pressure (LVEDP) and 38% increase in the time constant of pressure decay (P < 0.05) in these hearts, indicating a significant impairment of diastolic function. The increase in LVEDP was closely related to the increase in free [MgADP]. Rate of glycolysis was not changed, and [Ca2+]c increased by 16%, which cannot explain the severity of diastolic dysfunction. Thus, our data indicate that MgADP contributes significantly to diastolic dysfunction, possibly by slowing the rate of cross-bridge cycling. |
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Authors:
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R Tian; M E Christe; M Spindler; J C Hopkins; J M Halow; S A Camacho; J S Ingwall |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 99 ISSN: 0021-9738 ISO Abbreviation: J. Clin. Invest. Publication Date: 1997 Feb |
Date Detail:
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Created Date: 1997-03-20 Completed Date: 1997-03-20 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 745-51 Citation Subset: AIM; IM |
Affiliation:
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NMR Laboratory for Physiological Chemistry, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. rong@bustoff.bwh.harvard.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Diphosphate
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metabolism,
physiology* Animals Calcium / metabolism Diastole* Dose-Response Relationship, Drug Glycolysis Iodoacetamide / pharmacology Magnetic Resonance Spectroscopy Male Myocardial Reperfusion Myocardium / enzymology Rats Ventricular Dysfunction, Left / etiology*, metabolism, physiopathology* |
| Grant Support | |
ID/Acronym/Agency:
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HL 52350/HL/NHLBI NIH HHS; HL08973/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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144-48-9/Iodoacetamide; 58-64-0/Adenosine Diphosphate; 7440-70-2/Calcium |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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