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Impaired In Vivo Mitochondrial Krebs Cycle Activity Following Myocardial Infarction Assessed Using Hyperpolarized Magnetic Resonance Spectroscopy.
MedLine Citation:
PMID:  25201905     Owner:  NLM     Status:  Publisher    
BACKGROUND: -Myocardial infarction (MI) is one of the leading causes of heart failure. An increasing body of evidence links alterations in cardiac metabolism and mitochondrial function with the progression of heart disease. The aim of this work was to therefore follow the in vivo mitochondrial metabolic alterations caused by MI, thereby allowing a greater understanding of the interplay between metabolic and functional abnormalities.
METHODS AND RESULTS: -Using hyperpolarized carbon-13 ((13)C)-magnetic resonance spectroscopy, in vivo alterations in mitochondrial metabolism were assessed for 22 weeks following surgically induced MI with reperfusion in female Wister rats. One week post-MI, there were no detectable alterations in in vivo cardiac mitochondrial metabolism over the range of ejection fractions observed (from 28-84%). At 6 weeks post-MI, in vivo mitochondrial Krebs cycle activity was impaired, with decreased (13)C label flux into citrate, glutamate and acetylcarnitine, which correlated with the degree of cardiac dysfunction. These changes were independent of alterations in pyruvate dehydrogenase (PDH) flux. By 22 weeks, alterations were also seen in PDH flux, which decreased at lower ejection fractions. These results were confirmed using in vitro analysis of enzyme activities and metabolomic profiles of key intermediates.
CONCLUSIONS: -The in vivo decrease in Krebs cycle activity in the 6-week post-MI heart may represent an early maladaptive phase in the metabolic alterations following MI in which reductions in Krebs cycle activity precede a reduction in PDH flux. Changes in mitochondrial metabolism in heart disease are progressive and proportional to the degree of cardiac impairment.
Michael S Dodd; Helen J Atherton; Carolyn A Carr; Daniel J Stuckey; James A West; Julian L Griffin; George K Radda; Kieran Clarke; Lisa C Heather; Damian J Tyler
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-8
Journal Detail:
Title:  Circulation. Cardiovascular imaging     Volume:  -     ISSN:  1942-0080     ISO Abbreviation:  Circ Cardiovasc Imaging     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101479935     Medline TA:  Circ Cardiovasc Imaging     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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