This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 92/1/48    most recent 01.RES.0000049104.57549.03v1 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 Fallavollita, J. A. Articles by Canty, J. M. Search for Related Content PubMed PubMed Citation Articles by Fallavollita, J. A. Articles by Canty, J. M., Jr Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB EPINEPHRINE LACTIC ACID Related Collections Contractile function Animal models of human disease Chronic ischemic heart disease

Hibernating Myocardium Retains Metabolic and Contractile Reserve Despite Regional Reductions in Flow, Function, and Oxygen Consumption at Rest

From the VA Western New York Health Care System (J.A.F., J.M.C.) and the Departments of Medicine (J.A.F., B.J.M., J.M.C.) and Physiology & Biophysics (J.M.C.) at the University at Buffalo, NY.

Correspondence to James A. Fallavollita, MD, Biomedical Research Building, Room 347, Department of Medicine/Cardiology, University at Buffalo, 3435 Main St, Buffalo, NY 14214. E-mail jaf7{at}buffalo.edu

Hibernating myocardium, characterized by reductions in flow and function at rest, has limited contractile reserve in response to increases in external workload. We hypothesized that this attenuation of function reflects an adaptive downregulation that prevents the development of metabolic evidence of ischemia during stress. To test this hypothesis, pigs were chronically instrumented with a proximal left anterior descending artery stenosis for 3 months, resulting in severe anteroapical hypokinesis with reduced resting perfusion (0.78±0.05 versus 0.94±0.07 mL · min^-1 · g^-1 in remote, P<0.01; and 0.99±0.08 in controls, P<0.05). Open-chest studies confirmed resting dysfunction compared with normal controls (segment shortening 9.2±2.2% versus 23.5±1.1%, P<0.05). Resting myocardial oxygen consumption was reduced (63±3 versus 77±6 µL · g^-1 · min^-1 in controls, P<0.05), yet lactate consumption was normal. Although subendocardial perfusion failed to increase during graded, intravenous epinephrine infusion (n=8), peak segment shortening (to 17.3±3.1%, P<0.05) and oxygen consumption (to 90±6 µL · g^-1 · min^-1, P<0.01) increased from the depressed resting levels. There was no lactate production in hibernating myocardium, and lactate uptake increased during stress (0.7±0.1 to 1.2±0.1 µmol · g^-1 · min^-1, P<0.05). The absence of metabolic evidence of ischemia was also confirmed during atrial pacing to a rate of 120 bpm (n=8). Thus, despite reductions in function and oxygen consumption at rest, hibernating myocardium retains the ability to increase metabolism without the development of acute ischemia. This supports the hypothesis that the downregulation of oxygen consumption and function in hibernating myocardium is an adaptive response that prevents a supply-demand imbalance during submaximal increases in cardiac workload when coronary flow reserve is limited.

Key Words: hibernating myocardium • oxygen consumption • lactate • contractile reserve • ß-adrenergic stimulation

This article has been cited by other articles:

				Q. Hu, G. Suzuki, R. F. Young, B. J. Page, J. A. Fallavollita, and J. M. Canty Jr. Reductions in mitochondrial O2 consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H223 - H232. [Abstract] [Full Text] [PDF]

				D. J. Duncker and R. J. Bache Regulation of Coronary Blood Flow During Exercise Physiol Rev, July 1, 2008; 88(3): 1009 - 1086. [Abstract] [Full Text] [PDF]

				O. Sorop, D. Merkus, V. J. de Beer, B. Houweling, A. Pistea, E. O. McFalls, F. Boomsma, H. M. van Beusekom, W. J. van der Giessen, E. VanBavel, et al. Functional and Structural Adaptations of Coronary Microvessels Distal to a Chronic Coronary Artery Stenosis Circ. Res., April 11, 2008; 102(7): 795 - 803. [Abstract] [Full Text] [PDF]

				R. F. Kelly, W. Sluiter, and E. O. McFalls Hibernating Myocardium: Is the Program to Survive a Pathway to Failure? Circ. Res., January 4, 2008; 102(1): 3 - 5. [Full Text] [PDF]

				B. Page, R. Young, V. Iyer, G. Suzuki, M. Lis, L. Korotchkina, M. S. Patel, K. M. Blumenthal, J. A. Fallavollita, and J. M. Canty Jr Persistent Regional Downregulation in Mitochondrial Enzymes and Upregulation of Stress Proteins in Swine With Chronic Hibernating Myocardium Circ. Res., January 4, 2008; 102(1): 103 - 112. [Abstract] [Full Text] [PDF]

				E. O. McFalls, R. F. Kelly, Q. Hu, A. Mansoor, J. Lee, M. Kuskowski, J. Sikora, H. B. Ward, and J. Zhang The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2945 - H2951. [Abstract] [Full Text] [PDF]

				J. M. Canty Jr and V. S. Iyer Hydrogen Peroxide and Metabolic Coronary Flow Regulation J. Am. Coll. Cardiol., September 25, 2007; 50(13): 1279 - 1281. [Full Text] [PDF]

				P. Lynch, T.-C. Lee, J. A. Fallavollita, J. M. Canty Jr, and G. Suzuki Intracoronary Administration of AdvFGF-5 (Fibroblast Growth Factor-5) Ameliorates Left Ventricular Dysfunction and Prevents Myocyte Loss in Swine With Developing Collaterals and Ischemic Cardiomyopathy Circulation, September 11, 2007; 116(11_suppl): I-71 - I-76. [Abstract] [Full Text] [PDF]

				M. D. Banas, S. Baldwa, G. Suzuki, J. M. Canty Jr., and J. A. Fallavollita Determinants of contractile reserve in viable, chronically dysfunctional myocardium Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2791 - H2797. [Abstract] [Full Text] [PDF]

				V. S. Iyer and J. M. Canty Jr Regional Desensitization of {beta}-Adrenergic Receptor Signaling in Swine With Chronic Hibernating Myocardium Circ. Res., October 14, 2005; 97(8): 789 - 795. [Abstract] [Full Text] [PDF]

				V. Ovchinnikov, G. Suzuki, J. M. Canty Jr., and J. A. Fallavollita Blunted functional responses to pre- and postjunctional sympathetic stimulation in hibernating myocardium Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1719 - H1728. [Abstract] [Full Text] [PDF]

				P. Zong, J. D. Tune, and H. F. Downey Mechanisms of Oxygen Demand/Supply Balance in the Right Ventricle Experimental Biology and Medicine, September 1, 2005; 230(8): 507 - 519. [Abstract] [Full Text] [PDF]

				H. Wiggers, H. Norrelund, S. S. Nielsen, N. H. Andersen, J. E. Nielsen-Kudsk, J. S. Christiansen, T. T. Nielsen, N. Moller, and H. E. Botker Influence of insulin and free fatty acids on contractile function in patients with chronically stunned and hibernating myocardium Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H938 - H946. [Abstract] [Full Text] [PDF]

				E. R. Schwarz, R. Gupta, T. P. Diep, B. Nowak, S. Kostin, B. Grohmann, B. F. Uretsky, and J. Schaper Carvedilol Improves Myocardial Contractility Compared With Metoprolol in Patients With Chronic Hibernating Myocardium After Revascularization Journal of Cardiovascular Pharmacology and Therapeutics, July 1, 2005; 10(3): 181 - 190. [Abstract] [PDF]

				C. Waller, T. Engelhorn, K.-H. Hiller, G. Heusch, G. Ertl, W. R. Bauer, and R. Schulz Impaired resting perfusion in viable myocardium distal to chronic coronary stenosis in rats Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2588 - H2593. [Abstract] [Full Text] [PDF]

				G. Suzuki, T.-C. Lee, J. A. Fallavollita, and J. M. Canty Jr Adenoviral Gene Transfer of FGF-5 to Hibernating Myocardium Improves Function and Stimulates Myocytes to Hypertrophy and Reenter the Cell Cycle Circ. Res., April 15, 2005; 96(7): 767 - 775. [Abstract] [Full Text] [PDF]

				G. Heusch, R. Schulz, and S. H. Rahimtoola Myocardial hibernation: a delicate balance Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H984 - H999. [Abstract] [Full Text] [PDF]

				E. O. McFalls, M. Hou, R. J. Bache, A. Best, D. Marx, J. Sikora, and H. B. Ward Activation of p38 MAPK and increased glucose transport in chronic hibernating swine myocardium Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1328 - H1334. [Abstract] [Full Text] [PDF]

				J. Milei, C. G. Fraga, D. R. Grana, R. Ferreira, and G. Ambrosio Ultrastructural evidence of increased tolerance of hibernating myocardium to cardioplegic ischemia-reperfusion injury J. Am. Coll. Cardiol., June 16, 2004; 43(12): 2329 - 2336. [Abstract] [Full Text] [PDF]

				G. Heusch and K. R. Sipido Myocardial Hibernation: A Double-Edged Sword Circ. Res., April 30, 2004; 94(8): 1005 - 1007. [Full Text] [PDF]

				J. M. Canty Jr, G. Suzuki, M. D. Banas, F. Verheyen, M. Borgers, and J. A. Fallavollita Hibernating Myocardium: Chronically Adapted to Ischemia but Vulnerable to Sudden Death Circ. Res., April 30, 2004; 94(8): 1142 - 1149. [Abstract] [Full Text] [PDF]

				K. L. Gould, H. Taegtmeyer, Z.-X. He, R.-F. Shi, Y.-J. Wu, Y.-Q. Tian, X.-J. Liu, X.-W. Qin, R.-L. Gao, S.-W. Wang, et al. Myocardial Ischemia, Fluorodeoxyglucose, and Severity of Coronary Artery Stenosis: The Complexities of Metabolic Remodeling in Hibernating Myocardium * Response Circulation, March 30, 2004; 109(12): e167 - e170. [Full Text] [PDF]