AJP - Heart Calcium Transients and Cell-Sarcomere
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 287: H1538-H1543, 2004. First published June 10, 2004; doi:10.1152/ajpheart.00281.2004
0363-6135/04 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/4/H1538    most recent
00281.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (32)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chandler, M. P.
Right arrow Articles by Stanley, W. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chandler, M. P.
Right arrow Articles by Stanley, W. C.

Moderate severity heart failure does not involve a downregulation of myocardial fatty acid oxidation

Margaret P. Chandler,1 Janos Kerner,4 Hazel Huang,1 Edwin Vazquez,6 Aneta Reszko,2 Wenjun Z. Martini,1,4 Charles L. Hoppel,3,5,6 Makoto Imai,7 Sharad Rastogi,7 Hani N. Sabbah,7 and William C. Stanley1,4

Departments of 1Physiology and Biophysics, 2Biochemistry, 3Medicine, 4Nutrition, and 5Pharmacology, Case Western Reserve University and 6Medical Research Service, Louis Stokes Department of Veteran Affairs Medical Center, Cleveland, Ohio 44106; and 7Henry Ford Heart and Vascular Institute, Detroit, Michigan 48202

Submitted 23 March 2004 ; accepted in final form 8 June 2004

Recent human and animal studies have demonstrated that in severe end-stage heart failure (HF), the cardiac muscle switches to a more fetal metabolic phenotype, characterized by downregulation of free fatty acid (FFA) oxidation and an enhancement of glucose oxidation. The goal of this study was to examine myocardial substrate metabolism in a model of moderate coronary microembolization-induced HF. We hypothesized that during well-compensated HF, FFA oxidation would predominate as opposed to a more fetal metabolic phenotype of greater glucose oxidation. Cardiac substrate uptake and oxidation were measured in normal dogs (n = 8) and in dogs with microembolization-induced HF (n = 18, ejection fraction = 28%) by infusing three isotopic tracers ([9,10-3H]oleate, [U-14C]glucose, and [1-13C]lactate) in anesthetized open-chest animals. There were no differences in myocardial substrate metabolism between the two groups. The total activity of pyruvate dehydrogenase, the key enzyme regulating myocardial pyruvate oxidation (and hence glucose and lactate oxidation) was not affected by HF. We did not observe any difference in the activity of carnitine palmitoyl transferase I (CPT-I) and its sensitivity to inhibition by malonyl-CoA between groups; however, malonyl-CoA content was decreased by 22% with HF, suggesting less in vivo inhibition of CPT-I activity. The differences in malonyl-CoA content cannot be explained by changes in the Michaelis-Menten constant and maximal velocity for malonyl-CoA decarboxylase because neither were affected by HF. These results support the concept that there is no decrease in fatty acid oxidation during compensated HF and that the downregulation of fatty acid oxidation enzymes and the switch to carbohydrate oxidation observed in end-stage HF is only a late-stage phenomemon.

cardiac; metabolism; malonyl CoA


Address for reprint requests and other correspondence: W. C. Stanley, Dept. of Physiology and Biophysics, School of Medicine, Case Western Reserve Univ., 10900 Euclid Ave., Cleveland, OH 44106-4970 (E-mail: wcs4{at}po.cwru.edu)




This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
C. Pellieux, C. Montessuit, I. Papageorgiou, and R. Lerch
Angiotensin II downregulates the fatty acid oxidation pathway in adult rat cardiomyocytes via release of tumour necrosis factor-{alpha}
Cardiovasc Res, May 1, 2009; 82(2): 341 - 350.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
M. van Bilsen, F. A. van Nieuwenhoven, and G. J. van der Vusse
Metabolic remodelling of the failing heart: beneficial or detrimental?
Cardiovasc Res, February 15, 2009; 81(3): 420 - 428.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. M. O'Donnell, A. Fields, X. Xu, S. A. K. Chowdhury, D. L. Geenen, and J. Bi
Limited functional and metabolic improvements in hypertrophic and healthy rat heart overexpressing the skeletal muscle isoform of SERCA1 by adenoviral gene transfer in vivo
Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2483 - H2494.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
M. G. Rosca, E. J. Vazquez, J. Kerner, W. Parland, M. P. Chandler, W. Stanley, H. N. Sabbah, and C. L. Hoppel
Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative phosphorylation
Cardiovasc Res, October 1, 2008; 80(1): 30 - 39.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
H. Yamashita, K. G. Bharadwaj, S. Ikeda, T.-S. Park, and I. J. Goldberg
Cardiac metabolic compensation to hypertension requires lipoprotein lipase
Am J Physiol Endocrinol Metab, September 1, 2008; 295(3): E705 - E713.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
H. J. Eisen
Exercise Training and Myocardial Energetics in Patients With Heart Failure: When More Is Less
J. Am. Coll. Cardiol., May 13, 2008; 51(19): 1892 - 1895.
[Full Text] [PDF]

Home page
 CirculationHome page
H. Ashrafian, M. P. Frenneaux, and L. H. Opie
Metabolic Mechanisms in Heart Failure
Circulation, July 24, 2007; 116(4): 434 - 448.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
S. Neubauer
The Failing Heart -- An Engine Out of Fuel
N. Engl. J. Med., March 15, 2007; 356(11): 1140 - 1151.
[Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
J. D. Horowitz and J. A. Kennedy
Time to Address the Cardiac Metabolic "Triple Whammy": Ischemic Heart Failure in Diabetic Patients
J. Am. Coll. Cardiol., December 5, 2006; 48(11): 2232 - 2234.
[Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
W.H. W. Tang
Metabolic Approach in Heart Failure: Rethinking How We Translate From Theory to Clinical Practice
J. Am. Coll. Cardiol., September 5, 2006; 48(5): 999 - 1000.
[Full Text] [PDF]

Home page
 SEMIN CARDIOTHORAC VASC ANESTHHome page
G. D. Lopaschuk
Optimizing cardiac Fatty Acid and glucose metabolism as an approach to treating heart failure.
Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2006; 10(3): 228 - 230.
[Abstract] [PDF]

Home page
 Cardiovasc ResHome page
A. J. Murray, C. A. Lygate, M. A. Cole, C. A. Carr, G. K. Radda, S. Neubauer, and K. Clarke
Insulin resistance, abnormal energy metabolism and increased ischemic damage in the chronically infarcted rat heart
Cardiovasc Res, July 1, 2006; 71(1): 149 - 157.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
Y. Liao, S. Takashima, H. Zhao, Y. Asano, Y. Shintani, T. Minamino, J. Kim, M. Fujita, M. Hori, and M. Kitakaze
Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice
Cardiovasc Res, April 1, 2006; 70(1): 107 - 116.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
K. L. King, I. C. Okere, N. Sharma, J. R. B. Dyck, A. E. Reszko, T. A. McElfresh, J. Kerner, M. P. Chandler, G. D. Lopaschuk, and W. C. Stanley
Regulation of cardiac malonyl-CoA content and fatty acid oxidation during increased cardiac power
Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1033 - H1037.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
W. C. Stanley, F. A. Recchia, and G. D. Lopaschuk
Myocardial Substrate Metabolism in the Normal and Failing Heart
Physiol Rev, July 1, 2005; 85(3): 1093 - 1129.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.