HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/4/H1538    most recent 00281.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (22) Citing Articles via Google Scholar Google Scholar Articles by Chandler, M. P. Articles by Stanley, W. C. Search for Related Content PubMed PubMed Citation Articles by Chandler, M. P. Articles by Stanley, W. C.

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

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

This article has been cited by other articles:

				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]

				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, August 18, 2008; (2008) cvn184v1. [Abstract] [Full Text] [PDF]

				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]

				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]

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

				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]

				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]

				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]

				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]

				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]

				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]

				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]