Document Detail


Role of MgADP in the development of diastolic dysfunction in the intact beating rat heart.
MedLine Citation:
PMID:  9045879     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  99     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1997 Feb 
Date Detail:
Created Date:  1997-03-20     Completed Date:  1997-03-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  745-51     Citation Subset:  AIM; IM    
Affiliation:
NMR Laboratory for Physiological Chemistry, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. rong@bustoff.bwh.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / 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:
HL 52350/HL/NHLBI NIH HHS; HL08973/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
144-48-9/Iodoacetamide; 58-64-0/Adenosine Diphosphate; 7440-70-2/Calcium
Comments/Corrections

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