Circulation, Vol 81, 772-779, Copyright © 1990 by American Heart Association
CB Treasure, JA Vita, DA Cox, RD Fish, JB Gordon, GH Mudge, WS Colucci, MG Sutton, AP Selwyn and RW Alexander
Dilator reserve of the coronary microvasculature is diminished in patients
with dilated cardiomyopathy. Although increased extravascular compressive
forces, tachycardia, and increased myocardial mass can explain some
impairment, recent evidence suggests the possibility of intrinsic
microvascular disease. We tested the hypothesis that impairment of
endothelium-dependent dilation of the microvasculature could be a
contributing mechanism. We infused the endothelium-dependent dilator
acetylcholine (Ach) (10(-8) to 10(-6) M) and the smooth muscle vasodilator
adenosine (AD) (10(-6) to 10(-4) M) into the left anterior descending
coronary artery in eight patients with dilated cardiomyopathy (mean
ejection fraction, 28%) and seven controls (atypical chest pain). Small
vessel resistance was assessed by measuring coronary blood flow (CBF) at
constant arterial pressure with a Doppler velocity catheter (corrected for
cross-sectional area by angiography). With Ach, control patients increased
CBF 232 +/- 40% (mean +/- SEM), whereas CBF did not significantly change in
cardiomyopathy patients (41 +/- 24%) (p less than 0.0001, control vs.
cardiomyopathy). With AD, control patients increased CBF 422 +/- 56% and
cardiomyopathy patients increased CBF 268 +/- 43% (p = 0.13). An index of
the proportion of coronary flow reserve attributable to
endothelium-dependent vasodilation was obtained by standardizing each
patient's Ach dose response to his maximal AD flow response. In seven
control patients receiving both Ach and AD, 56 +/- 9% of the maximal AD
flow response was attained with the endothelium-dependent vasodilator Ach,
whereas in seven cardiomyopathy patients receiving both Ach and AD, only 23
+/- 14% of the maximal AD response was attained (p less than
0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Endothelium-dependent dilation of the coronary microvasculature is impaired in dilated cardiomyopathy
Department of Medicine (Cardiovascular Division), Brigham and Women's Hospital, Boston, MA 02115.
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P. R. A. Caramori, A. G. Adelman, E. R. Azevedo, G. E. Newton, A. B. Parker, and J. D. Parker Therapy with nitroglycerin increases coronary vasoconstriction in response to acetylcholine J. Am. Coll. Cardiol., December 1, 1998; 32(7): 1969 - 1974. [Abstract] [Full Text] [PDF]
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H. Drexler, S. Kastner, A. Strobel, R. Studer, O. E. Brodde, and G. Hasenfuss Expression, activity and functional significance of inducible nitric oxide synthase in the failing human heart J. Am. Coll. Cardiol., October 1, 1998; 32(4): 955 - 963. [Abstract] [Full Text] [PDF]
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A. Cooper and A. M. Heagerty Endothelial dysfunction in human intramyocardial small arteries in atherosclerosis and hypercholesterolemia Am J Physiol Heart Circ Physiol, October 1, 1998; 275(4): H1482 - H1488. [Abstract] [Full Text] [PDF]
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M. A. Mathier, G. A. Rose, M. A. Fifer, M. I. Miyamoto, R. E. Dinsmore, H. H. Castano, G. W. Dec, I. F. Palacios, and M. J. Semigran Coronary endothelial dysfunction in patients with acute-onset idiopathic dilated cardiomyopathy J. Am. Coll. Cardiol., July 1, 1998; 32(1): 216 - 224. [Abstract] [Full Text] [PDF]
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F. Costa and I. Biaggioni Role of Nitric Oxide in Adenosine-Induced Vasodilation in Humans Hypertension, May 1, 1998; 31(5): 1061 - 1064. [Abstract] [Full Text] [PDF]
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J. Wang, G.-H. Yi, M. Knecht, B.-l. Cai, S. Poposkis, M. Packer, and D. Burkhoff Physical Training Alters the Pathogenesis of Pacing-Induced Heart Failure Through Endothelium-Mediated Mechanisms in Awake Dogs Circulation, October 21, 1997; 96(8): 2683 - 2692. [Abstract] [Full Text]
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M. Mohri, K. Egashira, T. Tagawa, T. Kuga, H. Tagawa, Y. Harasawa, H. Shimokawa, and A. Takeshita Basal Release of Nitric Oxide Is Decreased in the Coronary Circulation in Patients With Heart Failure Hypertension, July 1, 1997; 30(1): 50 - 56. [Abstract] [Full Text]
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M. Veronneau, M. Tanguay, E. Fontaine, G. Jasmin, and L. Dumont Reactivity to endothelium-dependent and -independent vasoactive substances is maintained in coronary resistance vessels of the failing hamster heart Cardiovasc Res, March 1, 1997; 33(3): 623 - 630. [Abstract] [PDF]
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Y.-W. Xie, W. Shen, G. Zhao, X. Xu, M. S. Wolin, and T. H. Hintze Role of Endothelium-Derived Nitric Oxide in the Modulation of Canine Myocardial Mitochondrial Respiration In Vitro: Implications for the Development of Heart Failure Circ. Res., September 1, 1996; 79(3): 381 - 387. [Abstract] [Full Text]
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H. R. Figulla, F. Gietzen, U. Zeymer, M. Raiber, J. Hegselmann, R. Soballa, and R. Hilgers Diltiazem Improves Cardiac Function and Exercise Capacity in Patients With Idiopathic Dilated Cardiomyopathy: Results of the Diltiazem in Dilated Cardiomyopathy Trial Circulation, August 1, 1996; 94(3): 346 - 352. [Abstract] [Full Text]
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M. R. Kichuk, N. Seyedi, X. Zhang, C. C. Marboe, R. E. Michler, L. J. Addonizio, G. Kaley, A. Nasjletti, and T. H. Hintze Regulation of Nitric Oxide Production in Human Coronary Microvessels and the Contribution of Local Kinin Formation Circulation, July 1, 1996; 94(1): 44 - 51. [Abstract] [Full Text]
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D. E. Vatner, N. Sato, J. B. Galper, and S. F. Vatner Physiological and Biochemical Evidence for Coordinate Increases in Muscarinic Receptors and Gi During Pacing-Induced Heart Failure Circulation, July 1, 1996; 94(1): 102 - 107. [Abstract] [Full Text]
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C. R. Cannan, J. C. Burnett Jr, and A. Lerman Enhanced Coronary Vasoconstriction to Endothelin-BReceptor Activation in Experimental Congestive Heart Failure Circulation, February 15, 1996; 93(4): 646 - 651. [Abstract] [Full Text]
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C. J. Smith, D. Sun, C. Hoegler, B. S. Roth, X. Zhang, G. Zhao, X.-B. Xu, Y. Kobari, K. Pritchard Jr, W. C. Sessa, et al. Reduced Gene Expression of Vascular Endothelial NO Synthase and Cyclooxygenase-1 in Heart Failure Circ. Res., January 1, 1996; 78(1): 58 - 64. [Abstract] [Full Text]
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M.W. Ramsey, J. Goodfellow, C.J.H. Jones, L.A. Luddington, M.J. Lewis, and A.H. Henderson Endothelial Control of Arterial Distensibility Is Impaired in Chronic Heart Failure Circulation, December 1, 1995; 92(11): 3212 - 3219. [Abstract] [Full Text]
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P. Smits, S. B. Williams, D. E. Lipson, P. Banitt, G. A. Rongen, and M. A. Creager Endothelial Release of Nitric Oxide Contributes to the Vasodilator Effect of Adenosine in Humans Circulation, October 15, 1995; 92(8): 2135 - 2141. [Abstract] [Full Text]
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M. M.H. Marijianowski, M. van Laar, J. Bras, and A. E. Becker Chronic Congestive Heart Failure Is Associated With a Phenotypic Shift of Intramyocardial Endothelial Cells Circulation, September 15, 1995; 92(6): 1494 - 1498. [Abstract] [Full Text]
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D. Neglia, O. Parodi, M. Gallopin, G. Sambuceti, A. Giorgetti, L. Pratali, P. Salvadori, C. Michelassi, M. Lunardi, G. Pelosi, et al. Myocardial Blood Flow Response to Pacing Tachycardia and to Dipyridamole Infusion in Patients With Dilated Cardiomyopathy Without Overt Heart Failure : A Quantitative Assessment by Positron Emission Tomography Circulation, August 15, 1995; 92(4): 796 - 804. [Abstract] [Full Text]
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A. M. Zeiher, T. Krause, V. Schachinger, J. Minners, and E. Moser Impaired Endothelium-Dependent Vasodilation of Coronary Resistance Vessels Is Associated With Exercise-Induced Myocardial Ischemia Circulation, May 1, 1995; 91(9): 2345 - 2352. [Abstract] [Full Text]
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D. B. Haitsma, D. Merkus, J. Vermeulen, P. D. Verdouw, and D. J. Duncker Nitric oxide production is maintained in exercising swine with chronic left ventricular dysfunction Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2198 - H2209. [Abstract] [Full Text] [PDF]
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