(Circulation. 1995;91:2793-2801.)
© 1995 American Heart Association, Inc.
Articles |
Local Delivery of Vascular Endothelial Growth Factor Accelerates Reendothelialization and Attenuates Intimal Hyperplasia in Balloon-Injured Rat Carotid Artery
From the Departments of Medicine (Cardiology) (T.A., C.B., C.P., M.K., S.R., S.B., N.F., J.M.I), Surgery (Cardiovascular) (J.F.S.), and Biomedical Research (T.A., C.B., C.P., M.K., S.R., S.B., N.F., J.M.I.), St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass; and the Department of Cardiovascular Research (S.B., N.F.), Genentech, Inc, South San Francisco, Calif.
Correspondence to Jeffrey M. Isner, MD, St Elizabeth's Medical Center, 736 Cambridge St, Boston, MA 02135.
Background Most strategies designed to reduce restenosis by the use of pharmacological or biological reagents involve direct inhibition of vascular smooth muscle cell (SMC) proliferation. Alternatively, SMC proliferation might be indirectly inhibited if reendothelialization could be specifically facilitated at sites of balloon-induced arterial injury. Accordingly, we investigated the hypothesis that application of an endothelial cell (EC)-specific mitogen to a freshly denuded intimal surface could accelerate reendothelialization and thereby attenuate intimal hyperplasia.
Methods and Results The left carotid artery of 31 Sprague-Dawley rats was subjected to balloon injury, after which 16 rats were treated with a 30-minute incubation with 100 µg of vascular endothelial growth factor (VEGF), an EC-specific mitogen. Control animals (n=15) received a 30-minute incubation with 0.9% saline. At 2 weeks after balloon injury, carotid artery reendothelialization was markedly superior in the VEGF-treated group compared with the control group (14.59±1.12 versus 7.96±0.51 mm2, P<.0005). The extent of reendothelialization measured at 4 weeks after balloon injury remained superior for arteries treated with VEGF (18.04±0.90 mm2) versus saline (13.42±0.84 mm2, P<.005). Neointimal thickening was correspondingly attenuated to a statistically significant degree in arteries treated with VEGF versus the control group at both the 2-week and 4-week time points. Immunostaining for proliferating cell nuclear antigen (PCNA) disclosed a threefold increase in PCNA-positive cells in the neointima of control arteries versus VEGF-treated arteries at 2 weeks after injury.
Conclusions Application of VEGF, an EC-specific growth regulatory molecule, may be effectively used in vivo to promote reendothelialization and thereby indirectly attenuate neointimal thickening due to SMC proliferation.
Key Words: growth factors • endothelium • neointima • stenosis
This article has been cited by other articles:
 |
|
 |
|
  V. Mollace, S. Ragusa, I. Sacco, C. Muscoli, F. Sculco, V. Visalli, E. Palma, S. Muscoli, L. Mondello, P. Dugo, et al. The Protective Effect of Bergamot Oil Extract on Lecitine-like OxyLDL Receptor-1 Expression in Balloon Injury-related Neointima Formation Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2008; 13(2): 120 - 129. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Cyrus, H. Zhang, J. S. Allen, T. A. Williams, G. Hu, S. D. Caruthers, S. A. Wickline, and G. M. Lanza Intramural Delivery of Rapamycin With {alpha}v{beta}3-Targeted Paramagnetic Nanoparticles Inhibits Stenosis After Balloon Injury Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 820 - 826. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Szabo, J. Laki, H. O. Madsen, E. Dosa, Z. Prohaszka, S. Rugonfalvi-Kiss, M. Kokai, G. Acsadi, I. Karadi, L. Entz, et al. Early Rise in Serum VEGF and PDGF Levels Predisposes Patients With a Normal MBL2 Genotype to Restenosis After Eversion Endarterectomy Stroke, August 1, 2007; 38(8): 2247 - 2253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Shimojo, S. Jesmin, S. Zaedi, T. Otsuki, S. Maeda, N. Yamaguchi, K. Aonuma, Y. Hattori, and T. Miyauchi Contributory role of VEGF overexpression in endothelin-1-induced cardiomyocyte hypertrophy Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H474 - H481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. H. Walpoth, P. Zammaretti, M. Cikirikcioglu, E. Khabiri, M. K. Djebaili, J.-C. Pache, J.-C. Tille, Y. Aggoun, D. Morel, A. Kalangos, et al. Enhanced intimal thickening of expanded polytetrafluoroethylene grafts coated with fibrin or fibrin-releasing vascular endothelial growth factor in the pig carotid artery interposition model J. Thorac. Cardiovasc. Surg., May 1, 2007; 133(5): 1163 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Yla-Herttuala, T. T. Rissanen, I. Vajanto, and J. Hartikainen Vascular Endothelial Growth Factors: Biology and Current Status of Clinical Applications in Cardiovascular Medicine J. Am. Coll. Cardiol., March 13, 2007; 49(10): 1015 - 1026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ishikawa, M. Eguchi, M. Wada, Y. Iwami, K. Tono, H. Iwaguro, H. Masuda, T. Tamaki, and T. Asahara Establishment of a Functionally Active Collagen-Binding Vascular Endothelial Growth Factor Fusion Protein In Situ Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 1998 - 2004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Cheema, T. Hong, N. Nili, A. Segev, J. G. Moffat, K. E. Lipson, A. R. Howlett, D. W. Holdsworth, M. J. Cole, B. Qiang, et al. Adventitial Microvessel Formation After Coronary Stenting and the Effects of SU11218, a Tyrosine Kinase Inhibitor J. Am. Coll. Cardiol., March 7, 2006; 47(5): 1067 - 1075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tan, X. Jiang, F. Yang, Z. Li, D. Liao, J. Trial, M. J. Magera, W. Durante, X. Yang, and H. Wang Hyperhomocysteinemia inhibits post-injury reendothelialization in mice Cardiovasc Res, January 1, 2006; 69(1): 253 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Khurana, M. Simons, J. F. Martin, and I. C. Zachary Role of Angiogenesis in Cardiovascular Disease: A Critical Appraisal Circulation, September 20, 2005; 112(12): 1813 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gulati and R. D. Simari Cell Therapy for Angiogenesis: Embracing Diversity Circulation, September 13, 2005; 112(11): 1522 - 1524. [Full Text] [PDF]
|
|
|
|
 |
|
 W M Howell, S Ali, M J Rose-Zerilli, and S Ye VEGF polymorphisms and severity of atherosclerosis J. Med. Genet., June 1, 2005; 42(6): 485 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Costa and D. I. Simon Molecular Basis of Restenosis and Drug-Eluting Stents Circulation, May 3, 2005; 111(17): 2257 - 2273. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Morishita, M. Aoki, and T. Ogihara Does gene therapy become pharmacotherapy? Exp Physiol, May 1, 2005; 90(3): 307 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Luo, G. Y. Akita, T. Date, C. Treleaven, K. A. Vincent, D. Woodcock, S. H. Cheng, R. J. Gregory, and C. Jiang Adenovirus-Mediated Expression of {beta}-Adrenergic Receptor Kinase C-Terminus Reduces Intimal Hyperplasia and Luminal Stenosis of Arteriovenous Polytetrafluoroethylene Grafts in Pigs Circulation, April 5, 2005; 111(13): 1679 - 1684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Seipelt, C. L. Backer, C. Mavroudis, V. Stellmach, M. Cornwell, I. M. Seipelt, F. A. Schoendube, and S. E. Crawford Osteopontin expression and adventitial angiogenesis induced by local vascular endothelial growth factor 165 reduces experimental aortic calcification J. Thorac. Cardiovasc. Surg., April 1, 2005; 129(4): 773 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Simons Angiogenesis: Where Do We Stand Now? Circulation, March 29, 2005; 111(12): 1556 - 1566. [Full Text] [PDF]
|
|
|
|
|
|
K. Kappert, K. G. Peters, F. D. Bohmer, and A. Ostman Tyrosine phosphatases in vessel wall signaling Cardiovasc Res, February 15, 2005; 65(3): 587 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Shiojima and K. Walsh The Role of Vascular Endothelial Growth Factor in Restenosis: The Controversy Continues Circulation, October 19, 2004; 110(16): 2283 - 2286. [Full Text] [PDF]
|
|
|
|
|
|
R. Khurana, Z. Zhuang, S. Bhardwaj, M. Murakami, E. De Muinck, S. Yla-Herttuala, N. Ferrara, J. F. Martin, I. Zachary, and M. Simons Angiogenesis-Dependent and Independent Phases of Intimal Hyperplasia Circulation, October 19, 2004; 110(16): 2436 - 2443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hutter, F. E. Carrick, C. Valdiviezo, C. Wolinsky, J. S. Rudge, S. J. Wiegand, V. Fuster, J. J. Badimon, and B. V. Sauter Vascular Endothelial Growth Factor Regulates Reendothelialization and Neointima Formation in a Mouse Model of Arterial Injury Circulation, October 19, 2004; 110(16): 2430 - 2435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Muscoli, I. Sacco, W. Alecce, E. Palma, R. Nistico, N. Costa, F. Clementi, D. Rotiroti, F. Romeo, D. Salvemini, et al. The Protective Effect of Superoxide Dismutase Mimetic M40401 on Balloon Injury-Related Neointima Formation: Role of the Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 44 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yamaoka-Tojo, M. Ushio-Fukai, L. Hilenski, S. I. Dikalov, Y. E. Chen, T. Tojo, T. Fukai, M. Fujimoto, N. A. Patrushev, N. Wang, et al. IQGAP1, a Novel Vascular Endothelial Growth Factor Receptor Binding Protein, Is Involved in Reactive Oxygen Species--Dependent Endothelial Migration and Proliferation Circ. Res., August 6, 2004; 95(3): 276 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Raoul, B. Chailley-Heu, A.-M. Barlier-Mur, C. Delacourt, B. Maitre, and J. R. Bourbon Effects of vascular endothelial growth factor on isolated fetal alveolar type II cells Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1293 - L1301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Zeiffer, A. Schober, M. Lietz, E. A. Liehn, W. Erl, N. Emans, Z.-q. Yan, and C. Weber Neointimal Smooth Muscle Cells Display a Proinflammatory Phenotype Resulting in Increased Leukocyte Recruitment Mediated by P-Selectin and Chemokines Circ. Res., April 2, 2004; 94(6): 776 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Leppanen, J. Rutanen, M. O. Hiltunen, T. T. Rissanen, M. P. Turunen, T. Sjoblom, J. Bruggen, G. Backstrom, M. Carlsson, E. Buchdunger, et al. Oral Imatinib Mesylate (STI571/Gleevec) Improves the Efficacy of Local Intravascular Vascular Endothelial Growth Factor-C Gene Transfer in Reducing Neointimal Growth in Hypercholesterolemic Rabbits Circulation, March 9, 2004; 109(9): 1140 - 1146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Budhiraja, R. M. Tuder, and P. M. Hassoun Endothelial Dysfunction in Pulmonary Hypertension Circulation, January 20, 2004; 109(2): 159 - 165. [Full Text] [PDF]
|
|
|
|
|
|
A. Iwakura, C. Luedemann, S. Shastry, A. Hanley, M. Kearney, R. Aikawa, J. M. Isner, T. Asahara, and D. W. Losordo Estrogen-Mediated, Endothelial Nitric Oxide Synthase-Dependent Mobilization of Bone Marrow-Derived Endothelial Progenitor Cells Contributes to Reendothelialization After Arterial Injury Circulation, December 23, 2003; 108(25): 3115 - 3121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Matsuno, A. Ishisaki, K. Nakajima, K. Okada, S. Ueshima, O. Matsuo, and O. Kozawa Lack of {alpha}2-antiplasmin promotes re-endothelialization via over-release of VEGF after vascular injury in mice Blood, November 15, 2003; 102(10): 3621 - 3628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fujiyama, K. Amano, K. Uehira, M. Yoshida, Y. Nishiwaki, Y. Nozawa, D. Jin, S. Takai, M. Miyazaki, K. Egashira, et al. Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1-Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells Circ. Res., November 14, 2003; 93(10): 980 - 989. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gulati, D. Jevremovic, T. E. Peterson, T. A. Witt, L. S. Kleppe, C. S. Mueske, A. Lerman, R. G. Vile, and R. D. Simari Autologous Culture-Modified Mononuclear Cells Confer Vascular Protection After Arterial Injury Circulation, September 23, 2003; 108(12): 1520 - 1526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Seipelt, C. L. Backer, C. Mavroudis, V. Stellmach, I. M. Seipelt, M. Cornwell, J. Hernandez, and S. E. Crawford Topical VEGF Enhances Healing of Thoracic Aortic Anastomosis for Coarctation in a Rabbit Model Circulation, September 9, 2003; 108(90101): II-150 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Mata-Greenwood, B. Meyrick, S. J. Soifer, J. R. Fineman, and S. M. Black Expression of VEGF and its receptors Flt-1 and Flk-1/KDR is altered in lambs with increased pulmonary blood flow and pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, July 1, 2003; 285(1): L222 - L231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Sousa, M. A. Costa, and A. G.M.R. Sousa What Is "The Matter" With Restenosis in 2002? Circulation, June 25, 2002; 105(25): 2932 - 2933. [Full Text] [PDF]
|
|
|
|
|
|
D. H. Walter, K. Rittig, F. H. Bahlmann, R. Kirchmair, M. Silver, T. Murayama, H. Nishimura, D. W. Losordo, T. Asahara, and J. M. Isner Statin Therapy Accelerates Reendothelialization: A Novel Effect Involving Mobilization and Incorporation of Bone Marrow-Derived Endothelial Progenitor Cells Circulation, June 25, 2002; 105(25): 3017 - 3024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Lemstrom, R. Krebs, A. I. Nykanen, J. M. Tikkanen, R. K. Sihvola, E. M. Aaltola, P. J. Hayry, J. Wood, K. Alitalo, S. Yla-Herttuala, et al. Vascular Endothelial Growth Factor Enhances Cardiac Allograft Arteriosclerosis Circulation, May 28, 2002; 105(21): 2524 - 2530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-H. Liu, H. Jin, H. S. Floten, Z. Ren, A. P.C. Yim, and G.-W. He Vascular endothelial growth factor-mediated, endothelium-dependent relaxation in human internal mammary artery Ann. Thorac. Surg., March 1, 2002; 73(3): 819 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. I. Clyman, S. R. Seidner, H. Kajino, C. Roman, C. J. Koch, N. Ferrara, N. Waleh, F. Mauray, Y. Q. Chen, E. A. Perkett, et al. VEGF regulates remodeling during permanent anatomic closure of the ductus arteriosus Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2002; 282(1): R199 - R206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Freedman and J. M. Isner Therapeutic Angiogenesis for Coronary Artery Disease Ann Intern Med, January 1, 2002; 136(1): 54 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bassus, O. Herkert, N. Kronemann, A. Gorlach, D. Bremerich, C. M. Kirchmaier, R. Busse, and V. B. Schini-Kerth Thrombin Causes Vascular Endothelial Growth Factor Expression in Vascular Smooth Muscle Cells: Role of Reactive Oxygen Species Arterioscler. Thromb. Vasc. Biol., September 1, 2001; 21(9): 1550 - 1555. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Isner, P. R. Vale, J. F. Symes, and D. W. Losordo Assessment of Risks Associated With Cardiovascular Gene Therapy in Human Subjects Circ. Res., August 31, 2001; 89(5): 389 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rajagopalan, M. Shah, A. Luciano, R. Crystal, and E. G. Nabel Adenovirus-Mediated Gene Transfer of VEGF121 Improves Lower-Extremity Endothelial Function and Flow Reserve Circulation, August 14, 2001; 104(7): 753 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A.W. Broeders, P. A. Doevendans, J. G. Maessen, E. van Gorsel, M. G.A. O. Egbrink, M. J. A.P. Daemen, G. J. Tangelder, R. S. Reneman, and R. van der Zee The human internal thoracic artery releases more nitric oxide in response to vascular endothelial growth factor than the human saphenous vein J. Thorac. Cardiovasc. Surg., August 1, 2001; 122(2): 305 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Losordo and J. M. Isner Vascular endothelial growth factor-induced angiogenesis: crouching tiger or hidden dragon? J. Am. Coll. Cardiol., June 15, 2001; 37(8): 2131 - 2135. [Full Text] [PDF]
|
|
|
|
|
|
A. Farb, S. Shroff, M. John, W. Sweet, and R. Virmani Late Arterial Responses (6 and 12 Months) After 32P {beta}-Emitting Stent Placement : Sustained Intimal Suppression With Incomplete Healing Circulation, April 10, 2001; 103(14): 1912 - 1919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Zachary and G. Gliki Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family Cardiovasc Res, February 16, 2001; 49(3): 568 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sudoh, K. Toba, M. Akishita, J. Ako, M. Hashimoto, K. Iijima, S. Kim, Y.-Q. Liang, Y. Ohike, T. Watanabe, et al. Estrogen Prevents Oxidative Stress-Induced Endothelial Cell Apoptosis in Rats Circulation, February 6, 2001; 103(5): 724 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Matsumoto, R. Morishita, A. Moriguchi, N. Tomita, M. Aoki, H. Sakonjo, K. Matsumoto, T. Nakamura, J. Higaki, and T. Ogihara Inhibition of Neointima by Angiotensin-Converting Enzyme Inhibitor in Porcine Coronary Artery Balloon-Injury Model Hypertension, February 1, 2001; 37(2): 270 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Shibata, H. Kai, Y. Seki, S. Kato, M. Morimatsu, K. Kaibuchi, and T. Imaizumi Role of Rho-Associated Kinase in Neointima Formation After Vascular Injury Circulation, January 16, 2001; 103(2): 284 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Morita, H. Kurihara, S. Yoshida, Y. Saito, T. Shindo, Y. Oh-hashi, Y. Kurihara, Y. Yazaki, and R. Nagai Diet-Induced Hyperhomocysteinemia Exacerbates Neointima Formation in Rat Carotid Arteries After Balloon Injury Circulation, January 2, 2001; 103(1): 133 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Partovian, S. Adnot, B. Raffestin, V. Louzier, M. Levame, I. M. Mavier, P. Lemarchand, and S. Eddahibi Adenovirus-Mediated Lung Vascular Endothelial Growth Factor Overexpression Protects against Hypoxic Pulmonary Hypertension in Rats Am. J. Respir. Cell Mol. Biol., December 1, 2000; 23(6): 762 - 771. [Abstract] [Full Text]
|
|
|
|
|
|
B. Chandrasekar and J.-F. Tanguay Local delivery of 17-beta-estradiol decreases neointimal hyperplasia after coronary angioplasty in a porcine model J. Am. Coll. Cardiol., November 15, 2000; 36(6): 1972 - 1978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Meyerson, C. L. Skelly, M. A. Curi, and L. B. Schwartz Gene Therapy for Cardiovascular Disease Seminars in Cardiothoracic and Vascular Anesthesia, November 1, 2000; 4(4): 289 - 300. [Abstract] [PDF]
|
|
|
|
|
|
O. Leppanen, N. Janjic, M.-A. Carlsson, K. Pietras, M. Levin, C. Vargeese, L. S. Green, D. Bergqvist, A. Ostman, and C.-H. Heldin Intimal Hyperplasia Recurs After Removal of PDGF-AB and -BB Inhibition in the Rat Carotid Artery Injury Model Arterioscler. Thromb. Vasc. Biol., November 1, 2000; 20 (11): e89 - e95. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Hiltunen, M. Laitinen, M. P. Turunen, M. Jeltsch, J. Hartikainen, T. T. Rissanen, J. Laukkanen, M. Niemi, M. Kossila, T. P. Hakkinen, et al. Intravascular Adenovirus-Mediated VEGF-C Gene Transfer Reduces Neointima Formation in Balloon-Denuded Rabbit Aorta Circulation, October 31, 2000; 102(18): 2262 - 2268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.B.J Burton, V.J Owen, S Hafizi, P.J.R Barton, G Carr-White, T Koh, A De Souza, M.H Yacoub, and J.R Pepper Vascular endothelial growth factor release following coronary artery bypass surgery: extracorporeal circulation versus 'beating heart' surgery Eur. Heart J., October 2, 2000; 21(20): 1708 - 1713. [Abstract] [PDF]
|
|