Document Detail


Reduced myocardial creatine kinase flux in human myocardial infarction: an in vivo phosphorus magnetic resonance spectroscopy study.
MedLine Citation:
PMID:  19332463     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Energy metabolism is essential for myocellular viability. The high-energy phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr) are reduced in human myocardial infarction (MI), reflecting myocyte loss and/or decreased intracellular ATP generation by creatine kinase (CK), the prime energy reserve of the heart. The pseudo-first-order CK rate constant, k, measures intracellular CK reaction kinetics and is independent of myocyte number within sampled tissue. CK flux is defined as the product of [PCr] and k. CK flux and k have never been measured in human MI.
METHODS AND RESULTS: Myocardial CK metabolite concentrations, k, and CK flux were measured noninvasively in 15 patients 7 weeks to 16 years after anterior MI using phosphorus magnetic resonance spectroscopy. In patients, mean myocardial [ATP] and [PCr] were 39% to 44% lower than in 15 control subjects (PCr=5.4+/-1.2 versus 9.6+/-1.1 micromol/g wet weight in MI versus control subjects, respectively, P<0.001; ATP=3.4+/-1.1 versus 5.5+/-1.3 micromol/g wet weight, P<0.001). The myocardial CK rate constant, k, was normal in MI subjects (0.31+/-0.08 s(-1)) compared with control subjects (0.33+/-0.07 s(-1)), as was PCr/ATP (1.74+/-0.27 in MI versus 1.87+/-0.45). However, CK flux was halved in MI [to 1.7+/-0.5 versus 3.3+/-0.8 micromol(g . s)(-1); P<0.001].
CONCLUSIONS: These first observations of CK kinetics in prior human MI demonstrate that CK ATP supply is significantly reduced as a result of substrate depletion, likely attributable to myocyte loss. That k and PCr/ATP are unchanged in MI is consistent with the preservation of intracellular CK metabolism in surviving myocytes. Importantly, the results support therapies that primarily ameliorate the effects of tissue and substrate loss after MI and those that reduce energy demand rather than those that increase energy transfer or workload in surviving tissue.
Authors:
Paul A Bottomley; Katherine C Wu; Gary Gerstenblith; Steven P Schulman; Angela Steinberg; Robert G Weiss
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-03-30
Journal Detail:
Title:  Circulation     Volume:  119     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-14     Completed Date:  2009-05-14     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1918-24     Citation Subset:  AIM; IM    
Affiliation:
Division of MR Research, Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. bottoml@mri.jhu.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Adult
Creatine Kinase / metabolism*
Energy Metabolism
Humans
Kinetics
Magnetic Resonance Imaging / methods*
Male
Myocardial Infarction / enzymology*,  metabolism,  pathology*
Phosphocreatine / metabolism
Phosphorus
Reference Values
Grant Support
ID/Acronym/Agency:
2R01 HL56882/HL/NHLBI NIH HHS; 2R01 HL61912/HL/NHLBI NIH HHS; R01 HL056882-07/HL/NHLBI NIH HHS; R01 HL061912-08/HL/NHLBI NIH HHS; R01 HL061912-12/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
56-65-5/Adenosine Triphosphate; 67-07-2/Phosphocreatine; 7723-14-0/Phosphorus; EC 2.7.3.2/Creatine Kinase
Comments/Corrections

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