© 1995 American Heart Association, Inc.
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Mechanism of Impaired Myocardial Function During Progressive Coronary Stenosis in Conscious Pigs
Hibernation Versus Stunning?
From the Departments of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Mass, and the New England Regional Primate Research Center, Southborough, Mass.
Correspondence to Stephen F. Vatner, MD, Professor of Medicine, Harvard Medical School, New England Regional Primate Research Center, One Pine Hill Drive, PO Box 9102, Southborough, MA 01772-9102.
Abstract The major goal of this study was to determine whether impaired myocardial contractile function during the development of progressive coronary artery stenosis induced by ameroid constriction in conscious pigs reflected myocardial "hibernation" or "stunning." Minipigs were instrumented with a coronary ameroid constrictor and hydraulic occluder, regional wall thickness crystals, a left ventricular (LV) pressure gauge, and aortic and left atrial catheters. In the seven pigs in which it was measured, systolic wall thickening (WT) distal to the ameroid fell by a maximum of 56±6% at 20±3 days after ameroid implantation and then began to recover. At 1 day after ameroid implantation, brief complete coronary artery occlusion (CAO) resulted in wall thinning distal to the ameroid (-113±4%) and transmural decreases in myocardial blood flow in endocardial (from 0.82±0.08 to 0.02±0.01 mL/min per gram) and epicardial (from 0.73±0.13 to 0.03±0.02 mL/min per gram) layers. At 20±3 days, baseline myocardial blood flow was not altered either in endocardial (0.92±0.10 mL/min per gram) or epicardial (0.85±0.12 mL/min per gram) layers, whereas brief complete coronary artery occlusion still reduced WT (-83±12%) and myocardial blood flow in endocardial (to 0.21±0.03 mL/min per gram) and epicardial (to 0.43±0.12 mL/min per gram) layers, indicating that the coronary artery was not totally occluded. Pathology in four pigs demonstrated no gross necrotic myocardium shortly after this time point. Transient reductions in WT distal to the ameroid were observed during progressive coronary artery stenosis in response to spontaneous increases in activity. Beat-by-beat analysis of these episodes revealed that acute reductions in WT followed increases in LV dP/dt and heart rate and exhibited delayed recovery. These data suggest that the reduced function during ameroid-induced coronary stenosis reflected cumulative myocardial stunning rather than a primary deficit in coronary blood flow or "hibernating myocardium."
Key Words: myocardial blood flow • regional myocardial function • ischemia • oxygen supply/demand • ameroid constrictor
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
 G. HEUSCH Hibernating Myocardium Physiol Rev, October 1, 1998; 78(4): 1055 - 1085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 W. Wijns, S. F. Vatner, and P. G. Camici Hibernating Myocardium N. Engl. J. Med., July 16, 1998; 339(3): 173 - 181. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
R. K. Kudej, B. Ghaleh, N. Sato, Y.-T. Shen, S. P. Bishop, and S. F. Vatner Ineffective Perfusion-Contraction Matching in Conscious, Chronically Instrumented Pigs With an Extended Period of Coronary Stenosis Circ. Res., June 15, 1998; 82(11): 1199 - 1205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J Duncker, R. Schulz, R. Ferrari, D. Garcia-Dorado, C. Guarnieri, G. Heusch, and P. D Verdouw "Myocardial stunning": remaining questions Cardiovasc Res, June 1, 1998; 38(3): 549 - 558. [Full Text] [PDF]
|
|
|
|
|
|
G. Heusch, R. Ferrari, D. J Hearse, T. J.C Ruigrok, and R. Schulz 'Myocardial hibernation'--questions and controversies Cardiovasc Res, December 1, 1997; 36(3): 301 - 309. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
H. S. Silverman, S.-k. Wei, M. C. P. Haigney, C. J. Ocampo, and M. D. Stern Myocyte Adaptation to Chronic Hypoxia and Development of Tolerance to Subsequent Acute Severe Hypoxia Circ. Res., May 19, 1997; 80(5): 699 - 707. [Abstract] [Full Text]
|
|
|
|
|
|
J. A. Fallavollita, B. J. Perry, and J. M. Canty Jr 18F-2-Deoxyglucose Deposition and Regional Flow in Pigs With Chronically Dysfunctional Myocardium : Evidence for Transmural Variations in Chronic Hibernating Myocardium Circulation, April 1, 1997; 95(7): 1900 - 1909. [Abstract] [Full Text]
|
|
|
|
|
|
J.-L. J. Vanoverschelde, W. Wijns, M. Borgers, G. Heyndrickx, C. Depre, W. Flameng, and J. A. Melin Chronic Myocardial Hibernation in Humans: From Bedside to Bench Circulation, April 1, 1997; 95(7): 1961 - 1971. [Full Text]
|
|
|
|
|
|
B. L. Gerber, J.-L. J. Vanoverschelde, A. Bol, C. Michel, D. Labar, W. Wijns, and J. A. Melin Myocardial Blood Flow, Glucose Uptake, and Recruitment of Inotropic Reserve in Chronic Left Ventricular Ischemic Dysfunction: Implications for the Pathophysiology of Chronic Myocardial Hibernation Circulation, August 15, 1996; 94(4): 651 - 659. [Abstract] [Full Text]
|
|
|
|
|
|
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|
|
|
|
|
|
C. Chen, L. Chen, J. T. Fallon, L. Ma, L. Li, L. Bow, D. Knibbs, R. McKay, L. D. Gillam, and D. D. Waters Functional and Structural Alterations With 24-Hour Myocardial Hibernation and Recovery After Reperfusion: A Pig Model of Myocardial Hibernation Circulation, August 1, 1996; 94(3): 507 - 516. [Abstract] [Full Text]
|
|
|
|
|
|
E. Barnes, D. P. Dutka, M. Khan, P. G. Camici, and R. J. Hall Effect of repeated episodes of reversible myocardial ischemia on myocardial blood flow and function in humans Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1603 - H1608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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 |
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