Altered coronary vasodilator reserve and metabolism in myocardium subtended by normal arteries in patients with coronary artery disease

MRC Cyclotron Unit, Hammersmith Hospital, London, United Kingdom.

OBJECTIVES. The aim of this study was to investigate coronary vasodilator reserve and metabolism in myocardium subtended by angiographically normal arteries remote from ischemia. BACKGROUND. After infarction, structural and functional changes occur in remote myocardium often subtended by normal arteries. Whether changes occur in regions remote from ischemic but noninfarcted myocardium is unknown. METHODS. Coronary vasodilator reserve was measured with positron emission tomography in 12 patients with single-vessel disease using intravenous dipyridamole (0.56 mg/kg for 4 min). In another 10 patients, simultaneous arterial/great cardiac vein catheterization was performed during atrial pacing to measure myocardial metabolism in regions subtended by diseased or normal arteries. RESULTS. Basal myocardial blood flow in stenosis-related regions was comparable to that in remote regions but was lower after dipyridamole administration (1.73 +/- 0.91 vs. 2.89 +/- 0.93 ml/min per g, p < 0.01), giving coronary vasodilator reserve values of 1.80 +/- 0.82 and 2.73 +/- 0.89 (p < 0.01). In normal control subjects, basal myocardial blood flow was 0.92 +/- 0.13 and 3.67 +/- 0.94 ml/min per g in the basal state and after dipyridamole (both p < 0.05 vs. values in remote regions), and coronary vasodilator reserve was 4.07 +/- 0.98 (p < 0.01) vs. values in remote regions). During pacing there was net lactate release in diseased regions (-18 +/- 27%, p < 0.05 vs. values in remote regions and control subjects) and extraction in remote regions (38 +/- 17%) and in normal control subjects (26 +/- 11%). Glucose and alanine extraction were increased in diseased (8 +/- 6% and 6 +/- 6%) and remote regions (6 +/- 3% and 4 +/- 3%), compared with values in normal control subjects (2 +/- 3% and -1 +/- 3%, both p < 0.05 vs. diseased and remote regions). CONCLUSIONS. Coronary vasodilator reserve is reduced and glucose and alanine metabolism is abnormal in regions subtended by normal arteries remote from ischemic but noninfarcted myocardium.

This article has been cited by other articles:

				B. A. Herzog, L. Husmann, I. Valenta, O. Gaemperli, P. T. Siegrist, F. M. Tay, N. Burkhard, C. A. Wyss, and P. A. Kaufmann Long-Term Prognostic Value of (13)N-Ammonia Myocardial Perfusion Positron Emission Tomography Added Value of Coronary Flow Reserve. J. Am. Coll. Cardiol., July 7, 2009; 54(2): 150 - 156. [Abstract] [Full Text] [PDF]

				P. G. Camici and O. E. Rimoldi The Clinical Value of Myocardial Blood Flow Measurement J. Nucl. Med., July 1, 2009; 50(7): 1076 - 1087. [Abstract] [Full Text] [PDF]

				P. G. Camici and O. E. Rimoldi A Novel 18F-Labeled Tracer for the Quantification of Myocardial Blood Flow and Infarct Size With Positron-Emission Tomography: Another Way to Avoid the Need of an On-Site Cyclotron Circ Cardiovasc Imaging, March 1, 2009; 2(2): 75 - 76. [Full Text] [PDF]

				S. H. Rahimtoola, V. Dilsizian, C. M. Kramer, T. H. Marwick, and J.-L. J. Vanoverschelde Chronic ischemic left ventricular dysfunction from pathophysiology to imaging and its integration into clinical practice. J. Am. Coll. Cardiol. Img., July 1, 2008; 1(4): 536 - 555. [Abstract] [Full Text] [PDF]

				L. Wang, T. Y. Wong, A. R. Sharrett, R. Klein, A. R. Folsom, and M. Jerosch-Herold Relationship Between Retinal Arteriolar Narrowing and Myocardial Perfusion: Multi-Ethnic Study of Atherosclerosis Hypertension, January 1, 2008; 51(1): 119 - 126. [Abstract] [Full Text] [PDF]

				K. M. Marques, P. Knaapen, R. Boellaard, A. A. Lammertsma, N. Westerhof, and F. C. Visser Microvascular Function in Viable Myocardium After Chronic Infarction Does Not Influence Fractional Flow Reserve Measurements J. Nucl. Med., December 1, 2007; 48(12): 1987 - 1992. [Abstract] [Full Text] [PDF]

				A. Abbate, G. G.L. Biondi-Zoccai, P. Agostoni, M. J. Lipinski, and G. W. Vetrovec Recurrent angina after coronary revascularization: a clinical challenge Eur. Heart J., May 1, 2007; 28(9): 1057 - 1065. [Abstract] [Full Text] [PDF]

				P. G. Camici and F. Crea Coronary Microvascular Dysfunction N. Engl. J. Med., February 22, 2007; 356(8): 830 - 840. [Full Text] [PDF]

				J. J. Pacella and F. S. Villanueva Effect of Coronary Stenosis on Adjacent Bed Flow Reserve: Assessment of Microvascular Mechanisms Using Myocardial Contrast Echocardiography Circulation, October 31, 2006; 114(18): 1940 - 1947. [Abstract] [Full Text] [PDF]

				R Jagathesan, E Barnes, S D Rosen, R Foale, and P G Camici Dobutamine-induced hyperaemia inversely correlates with coronary artery stenosis severity and highlights dissociation between myocardial blood flow and oxygen consumption Heart, September 1, 2006; 92(9): 1230 - 1237. [Abstract] [Full Text] [PDF]

				D. Gazzieri, M. Trevisani, F. Tarantini, P. Bechi, G. Masotti, G. F. Gensini, S. Castellani, N. Marchionni, P. Geppetti, and S. Harrison Ethanol dilates coronary arteries and increases coronary flow via transient receptor potential vanilloid 1 and calcitonin gene-related peptide Cardiovasc Res, June 1, 2006; 70(3): 589 - 599. [Abstract] [Full Text] [PDF]

				C. J. Pepine, R. A. Kerensky, C. R. Lambert, K. M. Smith, G. O. von Mering, G. Sopko, and C. N. Bairey Merz Some Thoughts on the Vasculopathy of Women With Ischemic Heart Disease J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S30 - S35. [Abstract] [Full Text] [PDF]

				F. Tomai, F. Ribichini, A. S. Ghini, V. Ferrero, G. Ando, C. Vassanelli, F. Romeo, F. Crea, and L. Chiariello Elevated C-reactive protein levels and coronary microvascular dysfunction in patients with coronary artery disease Eur. Heart J., October 2, 2005; 26(20): 2099 - 2105. [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]

				P. A. Kaufmann and P. G. Camici Myocardial Blood Flow Measurement by PET: Technical Aspects and Clinical Applications J. Nucl. Med., January 1, 2005; 46(1): 75 - 88. [Full Text] [PDF]

				P. Koepfli, C. A. Wyss, M. Namdar, M. Klainguti, G. K. von Schulthess, T. F. Luscher, and P. A. Kaufmann {beta}-Adrenergic Blockade and Myocardial Perfusion in Coronary Artery Disease: Differential Effects in Stenotic Versus Remote Myocardial Segments J. Nucl. Med., October 1, 2004; 45(10): 1626 - 1631. [Abstract] [Full Text] [PDF]

				S. E. Langerak, H. W. Vliegen, J. W. Jukema, A. H. Zwinderman, H. J. Lamb, A. de Roos, and E. E. van der Wall Vein Graft Function Improvement after Percutaneous Intervention: Evaluation with MR Flow Mapping Radiology, September 1, 2003; 228(3): 834 - 841. [Abstract] [Full Text] [PDF]

				G. G. Neri Serneri, M. Boddi, P. A. Modesti, I. Cecioni, M. Coppo, M. L. Papa, T. Toscano, A. Marullo, and M. Chiavarelli Immunomediated and Ischemia-Independent Inflammation of Coronary Microvessels in Unstable Angina Circ. Res., June 27, 2003; 92(12): 1359 - 1366. [Abstract] [Full Text] [PDF]

				N. Spyrou, S. D. Rosen, F. Fath-Ordoubadi, R. Jagathesan, R. Foale, J. S. Kooner, and P. G. Camici Myocardial beta-adrenoceptor densityone month after acute myocardial infarctionpredicts left ventricular volumes at six months J. Am. Coll. Cardiol., October 2, 2002; 40(7): 1216 - 1224. [Abstract] [Full Text] [PDF]

				T. Ibrahim, S. G. Nekolla, K. Schreiber, K. Odaka, S. Volz, J. Mehilli, M. Guthlin, W. Delius, and M. Schwaiger Assessment of coronary flow reserve: comparison between contrast-enhanced magnetic resonance imaging and positron emission tomography J. Am. Coll. Cardiol., March 6, 2002; 39(5): 864 - 870. [Abstract] [Full Text] [PDF]

				F Chirillo, A Bruni, G Balestra, C Cavallini, Z Olivari, J D Thomas, and P Stritoni Assessment of internal mammary artery and saphenous vein graft patency and flow reserve using transthoracic Doppler echocardiography Heart, October 1, 2001; 86(4): 424 - 431. [Abstract] [Full Text] [PDF]

				G. S. Werner, M. Ferrari, B. M. Richartz, O. Gastmann, and H. R. Figulla Microvascular Dysfunction in Chronic Total Coronary Occlusions Circulation, September 4, 2001; 104(10): 1129 - 1134. [Abstract] [Full Text] [PDF]

				M Fujiwara, T Tamura, K Yoshida, K Nakagawa, M Nakao, M Yamanouchi, N Shikama, T Himi, and Y Masuda Coronary flow reserve in angiographically normal coronary arteries with one-vessel coronary artery disease without traditional risk factors Eur. Heart J., March 2, 2001; 22(6): 479 - 487. [Abstract] [PDF]

				M. Bottcher, M. M. Madsen, J. Refsgaard, N. H. Buus, I. Dorup, T. T. Nielsen, and K. Sorensen Peripheral Flow Response to Transient Arterial Forearm Occlusion Does Not Reflect Myocardial Perfusion Reserve Circulation, February 27, 2001; 103(8): 1109 - 1114. [Abstract] [Full Text] [PDF]

				D Pagano, F Fath-Ordoubadi, K J Beatt, J N Townend, R S Bonser, and P G Camici Effects of coronary revascularisation on myocardial blood flow and coronary vasodilator reserve in hibernating myocardium Heart, February 1, 2001; 85(2): 208 - 212. [Abstract] [Full Text]

				S. Sdringola, D. Patel, and K. L. Gould High Prevalence of Myocardial Perfusion Abnormalities on Positron Emission Tomography in Asymptomatic Persons With a Parent or Sibling With Coronary Artery Disease Circulation, January 30, 2001; 103(4): 496 - 501. [Abstract] [Full Text] [PDF]

				G. Sambuceti, A. L'Abbate, and M. Marzilli Why should we study the coronary microcirculation? Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2581 - H2584. [Full Text] [PDF]

				K. L. Gould, Y. Nakagawa, K. Nakagawa, S. Sdringola, M. J. Hess, M. Haynie, N. Parker, N. Mullani, and R. Kirkeeide Frequency and Clinical Implications of Fluid Dynamically Significant Diffuse Coronary Artery Disease Manifest as Graded, Longitudinal, Base-to-Apex Myocardial Perfusion Abnormalities by Noninvasive Positron Emission Tomography Circulation, April 25, 2000; 101(16): 1931 - 1939. [Abstract] [Full Text] [PDF]

				N. Al-Saadi, E. Nagel, M. Gross, A. Bornstedt, B. Schnackenburg, C. Klein, W. Klimek, H. Oswald, and E. Fleck Noninvasive Detection of Myocardial Ischemia From Perfusion Reserve Based on Cardiovascular Magnetic Resonance Circulation, March 28, 2000; 101(12): 1379 - 1383. [Abstract] [Full Text] [PDF]

				I. Kosa, R. Blasini, J. Schneider-Eicke, T. Dickfeld, F. J. Neumann, S. Ziegler, I. Matsunari, J. Neverve, A. Schomig, and M. Schwaiger Early recovery of coronary flow reserve after stent implantation as assessed by positron emission tomography J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1036 - 1041. [Abstract] [Full Text] [PDF]

				O.-P. Pitkanen, P. Nuutila, O. T. Raitakari, K. Porkka, H. Iida, I. Nuotio, T. Ronnemaa, J. Viikari, M.-R. Taskinen, C. Ehnholm, et al. Coronary Flow Reserve in Young Men With Familial Combined Hyperlipidemia Circulation, April 6, 1999; 99(13): 1678 - 1684. [Abstract] [Full Text] [PDF]

				Z S Kyriakides, A Antoniadis, T M Kolettis, and D T Kremastinos Coronary flow reserve in the contralateral artery increases after successful coronary angioplasty in patients with spontaneously visible collateral vessels Heart, November 1, 1998; 80(5): 493 - 498. [Abstract] [Full Text]

				G. S. Huggins, R. C. Pasternak, N. M. Alpert, A. J. Fischman, and H. Gewirtz Effects of Short-Term Treatment of Hyperlipidemia on Coronary Vasodilator Function and Myocardial Perfusion in Regions Having Substantial Impairment of Baseline Dilator Reverse Circulation, September 29, 1998; 98(13): 1291 - 1296. [Abstract] [Full Text] [PDF]

				K. Bhagat Endothelial function and myocardial infarction Cardiovasc Res, August 1, 1998; 39(2): 312 - 317. [Full Text] [PDF]

				H. Laine, O. T. Raitakari, H. Niinikoski, O.-P. Pitkanen, H. Iida, J. Viikari, P. Nuutila, and J. Knuuti Early impairment of coronary flow reserve in young men with borderline hypertension J. Am. Coll. Cardiol., July 1, 1998; 32(1): 147 - 153. [Abstract] [Full Text] [PDF]

				W. R. M. Aengevaeren, G. J. H. Uijen, J. W. Jukema, A. V. G. Bruschke, and T. van der Werf Functional Evaluation of Lipid-Lowering Therapy by Pravastatin in the Regression Growth Evaluation Statin Study (REGRESS) Circulation, July 15, 1997; 96(2): 429 - 435. [Abstract] [Full Text]

				K. L. Gould, D. Ornish, L. Scherwitz, S. Brown, R. P. Edens, M. J. Hess, N. Mullani, L. Bolomey, F. Dobbs, W. T. Armstrong, et al. Changes in Myocardial Perfusion Abnormalities by Positron Emission Tomography After Long-term, Intense Risk Factor Modification JAMA, September 20, 1995; 274(11): 894 - 901. [Abstract] [PDF]

				M. Di Carli, J. Czernin, C. K. Hoh, V. H. Gerbaudo, R. C. Brunken, S.-C. Huang, M. E. Phelps, and H. R. Schelbert Relation Among Stenosis Severity, Myocardial Blood Flow, and Flow Reserve in Patients With Coronary Artery Disease Circulation, April 1, 1995; 91(7): 1944 - 1951. [Abstract] [Full Text]

				N. G. Uren, T. Crake, D. C. Lefroy, R. de Silva, G. J. Davies, and A. Maseri Reduced Coronary Vasodilator Function in Infarcted and Normal Myocardium after Myocardial Infarction N. Engl. J. Med., July 28, 1994; 331(4): 222 - 227. [Abstract] [Full Text]

				N. G. Uren, J. A. Melin, B. De Bruyne, W. Wijns, T. Baudhuin, and P. G. Camici Relation between Myocardial Blood Flow and the Severity of Coronary-Artery Stenosis N. Engl. J. Med., June 23, 1994; 330(25): 1782 - 1788. [Abstract] [Full Text]