Document Detail

Decreased rates of substrate oxidation ex vivo predict the onset of heart failure and contractile dysfunction in rats with pressure overload.
MedLine Citation:
PMID:  20035032     Owner:  NLM     Status:  MEDLINE    
AIMS: Left ventricular hypertrophy is a risk factor for heart failure. However, it also is a compensatory response to pressure overload, accommodating for increased workload. We tested whether the changes in energy substrate metabolism may be predictive for the development of contractile dysfunction. METHODS AND RESULTS: Chronic pressure overload was induced in Sprague-Dawley rats by aortic arch constriction for 2, 6, 10, or 20 weeks. Contractile function in vivo was assessed by echocardiography and by invasive pressure measurement. Glucose and fatty acid oxidation as well as contractile function ex vivo were assessed in the isolated working heart, and respiratory capacity was measured in isolated cardiac mitochondria. Pressure overload caused progressive hypertrophy with normal ejection fraction (EF) at 2, 6, and 10 weeks, and hypertrophy with dilation and impaired EF at 20 weeks. The lung-to-body weight ratio, as marker for pulmonary congestion, was normal at 2 weeks (indicative of compensated hypertrophy) but significantly increased already after 6 and up to 20 weeks, suggesting the presence of heart failure with normal EF at 6 and 10 weeks and impaired EF at 20 weeks. Invasive pressure measurements showed evidence for contractile dysfunction already after 6 weeks and ex vivo cardiac power was reduced even at 2 weeks. Importantly, there was impairment in fatty acid oxidation beginning at 2 weeks, which was associated with a progressive decrease in glucose oxidation. In contrast, respiratory capacity of isolated mitochondria was normal until 10 weeks and decreased only in hearts with impaired EF. CONCLUSION: Pressure overload-induced impairment in fatty acid oxidation precedes the onset of congestive heart failure but mitochondrial respiratory capacity is maintained until the EF decreases in vivo. These temporal relations suggest a tight link between impaired substrate oxidation capacity in the development of heart failure and contractile dysfunction and may imply therapeutic and prognostic value.
Torsten Doenst; Gracjan Pytel; Andrea Schrepper; Paulo Amorim; Gloria F?rber; Yasushige Shingu; Friedrich W Mohr; Michael Schwarzer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-24
Journal Detail:
Title:  Cardiovascular research     Volume:  86     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-13     Completed Date:  2010-06-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  461-70     Citation Subset:  IM    
Department of Cardiac Surgery, University of Leipzig, Heart Center Leipzig, Str?mpellstr. 39, 04289 Leipzig, Germany.
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MeSH Terms
Blood Pressure
Cell Respiration
Disease Models, Animal
Energy Metabolism*
Fatty Acids / metabolism*
Glucose / metabolism*
Heart Failure / etiology*,  metabolism,  physiopathology
Hypertension / complications*,  metabolism
Hypertrophy, Left Ventricular / etiology,  metabolism,  physiopathology
Mitochondria, Heart / metabolism
Myocardial Contraction*
Myocardium / metabolism*,  pathology
Pulmonary Edema / etiology,  metabolism,  physiopathology
Rats, Sprague-Dawley
Stroke Volume
Time Factors
Ventricular Dysfunction, Left / etiology*,  metabolism,  physiopathology
Ventricular Function, Left
Reg. No./Substance:
0/Fatty Acids; 50-99-7/Glucose

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