This Article Full Text 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, J. Articles by Homans, D. C. Search for Related Content PubMed PubMed Citation Articles by Zhang, J. Articles by Homans, D. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

(Circulation. 1997;96:334-343.)
© 1997 American Heart Association, Inc.

Articles

Relationships Between Myocardial Bioenergetic and Left Ventricular Function in Hearts With Volume-Overload Hypertrophy

Jianyi Zhang, MD, PhD; Cynthia Toher, MD; Mark Erhard, MD; Yi Zhang, MD; Kamil Ugurbil, PhD; Robert J. Bache, MD; Thomas Lange, BS; ; David C. Homans, MD

From the Departments of Medicine, Cardiology Division (J.Z., C.T., M.E., K.U., R.J.B., T.L. D.C.H.), and Radiology (Y.Z., K.U.), University of Minnesota Medical School, Minneapolis.

Correspondence to Jianyi Zhang, MD, PhD, Cardiovascular Division, University of Minnesota Medical School, Box 508 UMHC, 420 Delaware St SE, Minneapolis, MN 55455. E-mail zhang047{at}maroon.tc.umn.edu

Background Left ventricular (LV) hypertrophy secondary to volume overload can result in alterations in myocardial bioenergetics and LV dysfunction. This study examined whether bioenergetic abnormalities contribute to the pump dysfunction.

Methods and Results Severe mitral regurgitation (MR) was produced in 10 dogs by disruption of the chordal apparatus. Hemodynamics and ventricular function were examined 11.7 months later under baseline conditions and during treadmill exercise. Myocardial high-energy phosphates were measured by using magnetic resonance spectroscopy at rest, during coronary vasodilation with adenosine, and during oxidative stress induced by rapid pacing and dobutamine. Chronic MR caused a 30% increase in LV mass and a 65% increase in LV volume. In MR animals, the hemodynamic and LV function were normal at rest, but abnormalities developed during ß-blockade and exercise. Myocardial creatine phosphate–to-ATP ratios were significantly lower in each layer across the LV wall in MR hearts than normal hearts. Myocardial blood flow and coronary reserve were normal in MR hearts. Moreover, hyperperfusion did not correct the abnormal bioenergetics. Despite altered bioenergetics at rest, the MR hearts tolerated rapid pacing and dobutamine infusion well.

Conclusions In volume-overloaded LV hypertrophied hearts, alterations in myocardial high-energy phosphate levels do not induce abnormal mechanical performance at rest but may be related to a decreased contractile reserve during exercise.

Key Words: mitral valve • regurgitation • phosphates • spectroscopy • heart failure

This article has been cited by other articles:

				H. Nagele, W. Rodiger, and M. A. Castel Rate-responsive pacing in patients with heart failure: long-term results of a randomized study Europace, October 1, 2008; 10(10): 1182 - 1188. [Abstract] [Full Text] [PDF]

				S. Gizurarson, M. Lorentzon, T. Ramunddal, F. Waagstein, L. Bergfeldt, and E. Omerovic Effects of complete heart block on myocardial function, morphology, and energy metabolism in the rat Europace, June 1, 2007; 9(6): 411 - 416. [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]

				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]

				S. Nemoto, P. Razeghi, M. Ishiyama, G. De Freitas, H. Taegtmeyer, and B. A. Carabello PPAR-{gamma} agonist rosiglitazone ameliorates ventricular dysfunction in experimental chronic mitral regurgitation Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H77 - H82. [Abstract] [Full Text] [PDF]

				A. V. Gourine, Q. Hu, P. R. Sander, A. I. Kuzmin, N. Hanafy, S. A. Davydova, D. V. Zaretsky, and J. Zhang Interstitial purine metabolites in hearts with LV remodeling Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H677 - H684. [Abstract] [Full Text] [PDF]

				J. A. Fallavollita, B. J. Malm, and J. M. Canty Jr Hibernating Myocardium Retains Metabolic and Contractile Reserve Despite Regional Reductions in Flow, Function, and Oxygen Consumption at Rest Circ. Res., January 10, 2003; 92(1): 48 - 55. [Abstract] [Full Text] [PDF]

				S. Nemoto, M. Hamawaki, G. De Freitas, and B. A. Carabello differential effects of the angiotensin-converting enzyme inhibitor lisinopril versus the beta-adrenergic receptor blocker atenolol on hemodynamics and left ventricular contractile function in experimental mitral regurgitation J. Am. Coll. Cardiol., July 3, 2002; 40(1): 149 - 154. [Abstract] [Full Text] [PDF]

				M. F.M van Oosterhout, T. Arts, J. B Bassingthwaighte, R. S Reneman, and F. W Prinzen Relation between local myocardial growth and blood flow during chronic ventricular pacing Cardiovasc Res, March 1, 2002; 53(4): 831 - 840. [Abstract] [Full Text] [PDF]

				M. Zaugg, M. C. Schaub, T. Pasch, and D. R. Spahn Modulation of {beta}-adrenergic receptor subtype activities in perioperative medicine: mechanisms and sites of action Br. J. Anaesth., January 1, 2002; 88(1): 101 - 123. [Abstract] [Full Text] [PDF]

				J. Liu, C. Wang, Y. Murakami, G. Gong, Y. Ishibashi, C. Prody, K. Ochiai, R. J. Bache, C. Godinot, and J. Zhang Mitochondrial ATPase and high-energy phosphates in failing hearts Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1319 - H1326. [Abstract] [Full Text] [PDF]

				S. C. Verduyn, C. Ramakers, G. Snoep, J. D. M. Leunissen, H. J. J. Wellens, and M. A. Vos Time course of structural adaptations in chronic AV block dogs: evidence for differential ventricular remodeling Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2882 - H2890. [Abstract] [Full Text] [PDF]

				Y. K. Cho, H. Merkle, J. Zhang, N. V. Tsekos, R. J. Bache, and K. Ugurbil Noninvasive measurements of transmural myocardial metabolites using 3-D 31P NMR spectroscopy Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H489 - H497. [Abstract] [Full Text] [PDF]

				J. Marin-Garcia, M. J Goldenthal, and G. W Moe Mitochondrial pathology in cardiac failure Cardiovasc Res, January 1, 2001; 49(1): 17 - 26. [Full Text] [PDF]

				K. D. Yi, H. F. Downey, X. Bian, M. Fu, and R. T. Mallet Dobutamine enhances both contractile function and energy reserves in hypoperfused canine right ventricle Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2975 - H2985. [Abstract] [Full Text] [PDF]

				M. Nagatsu, F. G. Spinale, M. Koide, H. Tagawa, G. DeFreitas, G. Cooper IV, and B. A. Carabello Bradycardia and the Role of {beta}-Blockade in the Amelioration of Left Ventricular Dysfunction Circulation, February 15, 2000; 101(6): 653 - 659. [Abstract] [Full Text] [PDF]

				Y. Murakami, J. Zhang, M. H. J. Eijgelshoven, W. Chen, W. C. Carlyle, Y. Zhang, G. Gong, and R. J. Bache Myocardial creatine kinase kinetics in hearts with postinfarction left ventricular remodeling Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H892 - H900. [Abstract] [Full Text] [PDF]