Circulation, Vol 87, 1513-1523, Copyright © 1993 by American Heart Association
JL Vanoverschelde, W Wijns, C Depre, B Essamri, GR Heyndrickx, M Borgers, A Bol and JA Melin
BACKGROUND. Even in the absence of a previous myocardial infarction,
patients with coronary artery disease often present with chronic regional
wall motion abnormalities that are reversible spontaneously or after
coronary revascularization. In these patients, regional dysfunction has
been proposed to result either from prolonged postischemic dysfunction
(myocardial "stunning") or from adaptation to chronic hypoperfusion
(myocardial "hibernation"). This study examines which of these two
mechanisms is responsible for the chronic regional dysfunction often
detected in patients with angina and noninfarcted collateral-dependent
myocardium. METHODS AND RESULTS. Twenty-six anginal patients (19 men; mean
age, 60 +/- 9 years old) with chronic occlusion of a major coronary artery
but without previous infarction were studied. Positron emission tomography
was performed to measure absolute regional myocardial blood flow with
13N-ammonia at rest (n = 26) and after intravenous dipyridamole (n = 11).
The kinetics of 18F- deoxyglucose and 11C-acetate were measured to
calculate the rate of exogenous glucose uptake and the regional oxidative
metabolism (n = 15). Global and regional left ventricular function was
evaluated by contrast ventriculography at baseline (n = 26) and after
revascularization (n = 12). Transmural myocardial biopsies from the
collateral-dependent area were obtained in seven patients during bypass
surgery and analyzed by optical and electron microscopy. According to
resting regional wall motion, patients were separated into groups with and
without dysfunction of the collateral-dependent segments. In patients with
normal wall motion (n = 9), regional myocardial blood flow, oxidative
metabolism, and glucose uptake were similar among collateral-dependent and
remote segments. By contrast, in patients with regional dysfunction (n =
17), collateral-dependent segments had lower myocardial blood flow (77 +/-
25 versus 95 +/- 27 mL.min-1.100 g-1, p < 0.001), smaller k values
(slope of 11C clearance reflecting oxidative metabolism, 0.049 +/- 0.015
versus 0.068 +/- 0.020 min-1, p < 0.001) and higher glucose uptake
(relative 18F-deoxyglucose-to-flow ratio of 1.9 +/- 1.6 versus 1.2 +/- 0.2,
p < 0.05) compared with remote segments. However, myocardial blood flow
and k values were similar among collateral-dependent segments of patients
with and without segmental dysfunction. After intravenous dipyridamole,
collateral- dependent myocardial blood flow increased from 78 +/- 5 to 238
+/- 54 mL.min-1.100 g-1 in three patients with normal wall motion and from
88 +/- 17 to only 112 +/- 44 mL.min-1.100 g-1 in eight patients with
regional dysfunction. There was a significant (r = -0.85, p < 0.001)
inverse correlation between wall motion abnormality and collateral flow
reserve. Analysis of the tissue samples obtained at the time of bypass
surgery showed profound structural changes in dysfunctioning collateral-
dependent areas, including cellular swelling, loss of myofibrillar content,
and accumulation of glycogen. Despite these alterations, the regional wall
motion score improved significantly in the patients studied before and
after revascularization (from 3.8 +/- 1.3 to 0.8 +/- 0.9, p < 0.005).
CONCLUSIONS. In a subgroup of patients with noninfarcted
collateral-dependent myocardium, immature or insufficiently developed
collaterals do not provide adequate flow reserve. Despite nearly normal
resting flow and oxygen consumption, these collateral-dependent segments
exhibit chronically depressed wall motion and demonstrate marked
ultrastructural alterations on morphological analysis. We propose that
these alterations result from repeated episodes of ischemia as opposed to
chronic hypoperfusion and represent the flow, metabolic, and morphological
correlates of myocardial "hibernation."
ARTICLES
Mechanisms of chronic regional postischemic dysfunction in humans. New insights from the study of noninfarcted collateral-dependent myocardium
Division of Cardiology, University of Louvain Medical School, Brussels, Belgium.
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R Schulz and G Heusch Hibernating myocardium Heart, December 1, 2000; 84(6): 587 - 594. [Full Text]
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J.-P. Bin, R. A. Pelberg, K. Wei, M. Coggins, N. C. Goodman, and S. Kaul Relation between regional function and coronary blood flow reserve in multivessel coronary artery stenosis Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H3058 - H3064. [Abstract] [Full Text] [PDF]
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J. Narula, M. S. Dawson, B. K. Singh, A. Amanullah, E. R. Acio, F. A. Chaudhry, R. B. Arani, and A. E. Iskandrian Noninvasive characterization of stunned, hibernating, remodeled and nonviable myocardium in ischemic cardiomyopathy J. Am. Coll. Cardiol., November 15, 2000; 36(6): 1913 - 1919. [Abstract] [Full Text] [PDF]
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N. H.J. Pijls, B. De Bruyne, G. J. W. Bech, F. Liistro, G. R. Heyndrickx, H. J.R.M. Bonnier, and J. J. Koolen Coronary Pressure Measurement to Assess the Hemodynamic Significance of Serial Stenoses Within One Coronary Artery : Validation in Humans Circulation, November 7, 2000; 102(19): 2371 - 2377. [Abstract] [Full Text] [PDF]
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M. Simons, R. O. Bonow, N. A. Chronos, D. J. Cohen, F. J. Giordano, H. K. Hammond, R. J. Laham, W. Li, M. Pike, F. W. Sellke, et al. Clinical Trials in Coronary Angiogenesis: Issues, Problems, Consensus : An Expert Panel Summary Circulation, September 12, 2000; 102 (11): e73 - e86. [Abstract] [Full Text] [PDF]
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J. A. Fallavollita, C. Trojan, and J. M. Canty Jr. Transmural distribution of FDG uptake in stunned myocardium Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H102 - H109. [Abstract] [Full Text] [PDF]
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S. Borges-Neto, A. Javaid, L. K. Shaw, D. F. Kong, M. W. Hanson, R. A. Pagnanelli, G. Ravizzini, and R. E. Coleman Poststress Measurements of Left Ventricular Function with Gated Perfusion SPECT: Comparison with Resting Measurements by Using a Same-Day Perfusion-Function Protocol Radiology, May 1, 2000; 215(2): 529 - 533. [Abstract] [Full Text]
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B. De Bruyne, N. H. J. Pijls, G. R. Heyndrickx, D. Hodeige, R. Kirkeeide, and K. L. Gould Pressure-Derived Fractional Flow Reserve to Assess Serial Epicardial Stenoses : Theoretical Basis and Animal Validation Circulation, April 18, 2000; 101(15): 1840 - 1847. [Abstract] [Full Text] [PDF]
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D Pagano, J N Townend, D V Parums, R S Bonser, and P G Camici Hibernating myocardium: morphological correlates of inotropic stimulation and glucose uptake Heart, April 1, 2000; 83(4): 456 - 461. [Abstract] [Full Text]
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E Barnes, C S R Baker, D P Dutka, O Rimoldi, C A Rinaldi, P Nihoyannopoulos, P G Camici, and R J C Hall Prolonged left ventricular dysfunction occurs in patients with coronary artery disease after both dobutamine and exercise induced myocardial ischaemia Heart, March 1, 2000; 83(3): 283 - 289. [Abstract] [Full Text]
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P. H. McNulty, D. Jagasia, G. W. Cline, C. K. Ng, J. M. Whiting, P. Garg, G. I. Shulman, and R. Soufer Persistent Changes in Myocardial Glucose Metabolism In Vivo During Reperfusion of a Limited-Duration Coronary Occlusion Circulation, February 29, 2000; 101(8): 917 - 922. [Abstract] [Full Text] [PDF]
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D. D’Arcangelo, F. Facchiano, L. M. Barlucchi, G. Melillo, B. Illi, L. Testolin, C. Gaetano, and M. C. Capogrossi Acidosis Inhibits Endothelial Cell Apoptosis and Function and Induces Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor Expression Circ. Res., February 18, 2000; 86(3): 312 - 318. [Abstract] [Full Text] [PDF]
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 J. D. Symons, S. V. Rendig, C. L. Stebbins, and J. C. Longhurst Microvascular and myocardial contractile responses to ischemia: influence of exercise training J Appl Physiol, February 1, 2000; 88(2): 433 - 442. [Abstract] [Full Text] [PDF]
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A. F. M. van den Heuvel, D. J. van Veldhuisen, E. E. van der Wall, P. K. Blanksma, H.-M. J. Siebelink, W. M. Vaalburg, W. H. van Gilst, and H. J. G. M. Crijns Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy J. Am. Coll. Cardiol., January 1, 2000; 35(1): 19 - 28. [Abstract] [Full Text] [PDF]
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C. Seiler, M. Fleisch, M. Billinger, and B. Meier Simultaneous intracoronary velocity- and pressure-derived assessment of adenosine-induced collateral hemodynamics in patients with one- to two-vessel coronary artery disease J. Am. Coll. Cardiol., December 1, 1999; 34(7): 1985 - 1994. [Abstract] [Full Text] [PDF]
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B. Shivalkar, W. Flameng, M. Szilard, S. Pislaru, M. Borgers, and J. Vanhaecke Repeated stunning precedes myocardial hibernation in progressive multiple coronary artery obstruction J. Am. Coll. Cardiol., December 1, 1999; 34(7): 2126 - 2136. [Abstract] [Full Text] [PDF]
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R Senior and A Lahiri Dobutamine echocardiography predicts functional outcome after revascularisation in patients with dysfunctional myocardium irrespective of the perfusion pattern on resting thallium-201 imaging Heart, December 1, 1999; 82(6): 668 - 673. [Abstract] [Full Text]
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J. A. Fallavollita, S. Jacob, R. F. Young, and J. M. Canty Jr. Regional alterations in SR Ca2+-ATPase, phospholamban, and HSP-70 expression in chronic hibernating myocardium Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1418 - H1428. [Abstract] [Full Text] [PDF]
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G. D. Dispersyn, J. Ausma, F. Thone, W. Flameng, J.-L. J. Vanoverschelde, M. A. Allessie, F. C.S. Ramaekers, and M. Borgers Cardiomyocyte remodelling during myocardial hibernation and atrial fibrillation: prelude to apoptosis Cardiovasc Res, September 1, 1999; 43(4): 947 - 957. [Abstract] [Full Text] [PDF]
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S. F. Nagueh, I. Mikati, D. Weilbaecher, M. J. Reardon, G. J. Al-Zaghrini, D. Cacela, Z.-X. He, G. Letsou, G. Noon, J. F. Howell, et al. Relation of the Contractile Reserve of Hibernating Myocardium to Myocardial Structure in Humans Circulation, August 3, 1999; 100(5): 490 - 496. [Abstract] [Full Text] [PDF]
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F Fath-Ordoubadi, K J Beatt, N Spyrou, and P G Camici Efficacy of coronary angioplasty for the treatment of hibernating myocardium Heart, August 1, 1999; 82(2): 210 - 216. [Abstract] [Full Text] [PDF]
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J. M. Canty Jr. and J. A. Fallavollita Resting myocardial flow in hibernating myocardium: validating animal models of human pathophysiology Am J Physiol Heart Circ Physiol, July 1, 1999; 277(1): H417 - H422. [Full Text] [PDF]
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The CHRISTMAS Study Steering Committee and Investi, J. G.F. Cleland, D. Pennel, S. Ray, G. Murray, P. MacFarlane, A. Cowley, A. Coats, and A. Lahiri The Carvedilol Hibernation Reversible Ischaemia Trial; Marker of Success (CHRISTMAS) Eur J Heart Fail, June 1, 1999; 1(2): 191 - 196. [Abstract] [Full Text] [PDF]
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J. A. Fallavollita and J. M. Canty Jr Differential 18F-2-Deoxyglucose Uptake in Viable Dysfunctional Myocardium With Normal Resting Perfusion : Evidence for Chronic Stunning in Pigs Circulation, June 1, 1999; 99(21): 2798 - 2805. [Abstract] [Full Text] [PDF]
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G. Holmvang, S. Fry, H. A. Skopicki, S. A. Abraham, N. M. Alpert, A. J. Fischman, M. H. Picard, and H. Gewirtz Relation Between Coronary "Steal" and Contractile Function at Rest in Collateral-Dependent Myocardium of Humans With Ischemic Heart Disease Circulation, May 18, 1999; 99(19): 2510 - 2516. [Abstract] [Full Text] [PDF]
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H. Schoder, R. Campisi, T. Ohtake, C. K. Hoh, D. H. Moon, J. Czernin, and H. R. Schelbert Blood flow-metabolism imaging with positron emission tomography in patients with diabetes mellitus for the assessment of reversible left ventricular contractile dysfunction J. Am. Coll. Cardiol., April 1, 1999; 33(5): 1328 - 1337. [Abstract] [Full Text] [PDF]
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