Circulation. 2002;105:2012-2018
Published online before print April 15, 2002, doi: 10.1161/01.CIR.0000015982.70785.B7
Published online before print April 15, 2002, doi: 10.1161/01.CIR.0000015982.70785.B7
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;105:2012.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Phase 1/2 Placebo-Controlled, Double-Blind, Dose-Escalating Trial of Myocardial Vascular Endothelial Growth Factor 2 Gene Transfer by Catheter Delivery in Patients With Chronic Myocardial Ischemia
From the Divisions of Cardiology (D.W.L., P.R.V., N.C., T.A., J.M.I.) and Cardiovascular Research (D.W.L., P.R.V., J.M.I., C.E.M.) Tufts School of Medicine/St Elizabeth’s Medical Center, Boston, Mass; Division of Cardiology, Rush-Presbyterian–St Luke’s Medical Center (R.C.H.), Chicago, Ill; Department of Cardiology, Scripps Clinic (F.D.F., R.A.S.), La Jolla, Calif; Harvard Medical School Division of Biometrics, Brigham and Women’s Hospital (R.E.K.), Boston, Mass.
Correspondence to Douglas W. Losordo, MD, St Elizabeth’s Medical Center, 736 Cambridge St, Boston, MA 02135. E-mail douglas.losordo{at}tufts.edu
Background— This phase 1/2 study investigated the safety of percutaneous catheter-based gene transfer of naked plasmid DNA encoding for vascular endothelial growth factor 2 (phVEGF2) to left ventricular (LV) myocardium in a prospective, randomized, double-blind, placebo-controlled, dose-escalating study of inoperable patients with class III or IV angina.
Methods and Results— A steerable deflectable 8F catheter with a 27-gauge needle at its distal tip was advanced percutaneously to the endocardial surface of the LV in 19 patients (age, 61±2 years) with chronic myocardial ischemia who were not candidates for conventional revascularization. Patients were randomized in a double-blind fashion to receive 6 injections (total volume, 6.0 mL) of placebo or phVEGF2 in doses of 200 µg (n=9), 800 µg (n=9), or 2000 µg (n=1) guided by LV electromechanical (NOGA) mapping with a gene-to-placebo ratio of 2:1. A total of 114 LV injections were delivered and caused no hemodynamic alterations, sustained ventricular arrhythmias, ECG evidence of infarction, or ventricular perforation. End-point analysis at 12 weeks disclosed a statistically significant improvement in Canadian Cardiovascular Society (CCS) angina class in phVEGF2-treated versus placebo-treated patients (-1.3 versus -0.1, P=0.04). Remaining efficacy end points—including change in exercise duration (91.8 versus 3.9 seconds), functional improvement by 
2 CCS classes (9 of 12 versus 1 of 6), and Seattle Angina Questionnaire data—all showed strong trends favoring efficacy of phVEGF2 versus placebo treatment.
Conclusions— This phase 1/2, double-blind, randomized trial provides preliminary data that support safety of phVEGF2 catheter-mediated myocardial gene transfer. The statistically significant reduction in anginal class and strong positive trends for remaining end points suggest that a larger phase 2/3 trial is warranted.
Key Words: growth substances • gene therapy • ischemia • angina • angiogenesis
This article has been cited by other articles:
 |
|
 |
|
  W. Schgoer, M. Theurl, J. Jeschke, A. G.E. Beer, K. Albrecht, R. Gander, S. Rong, D. Vasiljevic, M. Egger, A. M. Wolf, et al. Gene Therapy With the Angiogenic Cytokine Secretoneurin Induces Therapeutic Angiogenesis by a Nitric Oxide-Dependent Mechanism Circ. Res., November 6, 2009; 105(10): 994 - 1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gupta, J. Tongers, and D. W. Losordo Human Studies of Angiogenic Gene Therapy Circ. Res., October 9, 2009; 105(8): 724 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, L. Ding, Y. Zhao, W. Sun, B. Chen, H. Lin, X. Wang, L. Zhang, B. Xu, and J. Dai Collagen-Targeting Vascular Endothelial Growth Factor Improves Cardiac Performance After Myocardial Infarction Circulation, April 7, 2009; 119(13): 1776 - 1784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Lavine and D. M. Ornitz Shared Circuitry: Developmental Signaling Cascades Regulate Both Embryonic and Adult Coronary Vasculature Circ. Res., January 30, 2009; 104(2): 159 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Birk, J. Barbato, L. Mureebe, and R. A. Chaer Basic Science Review: Current Insights on the Biology and Clinical Aspects of VEGF Regulation Vascular and Endovascular Surgery, January 1, 2009; 42(6): 517 - 530. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Saeed, A. Martin, A. Jacquier, M. Bucknor, D. Saloner, L. Do, P. Ursell, H. Su, Y. W. Kan, and C. B. Higgins Permanent Coronary Artery Occlusion: Cardiovascular MR Imaging Is Platform for Percutaneous Transendocardial Delivery and Assessment of Gene Therapy in Canine Model Radiology, November 1, 2008; 249(2): 560 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Baldazzi, E. Jorgensen, R. S. Ripa, and J. Kastrup Release of biomarkers of myocardial damage after direct intramyocardial injection of genes and stem cells via the percutaneous transluminal route Eur. Heart J., August 1, 2008; 29(15): 1819 - 1826. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Sinusas Targeted imaging offers advantages over physiological imaging for evaluation of angiogenic therapy. J. Am. Coll. Cardiol. Img., July 1, 2008; 1(4): 511 - 514. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kinnaird, E. Stabile, S. Zbinden, M.-S. Burnett, and S. E. Epstein Cardiovascular risk factors impair native collateral development and may impair efficacy of therapeutic interventions Cardiovasc Res, May 1, 2008; 78(2): 257 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hobo, T. Shimizu, H. Sekine, T. Shin'oka, T. Okano, and H. Kurosawa Therapeutic Angiogenesis Using Tissue Engineered Human Smooth Muscle Cell Sheets Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): 637 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Johnson, L. Schofield, T. Donahay, M. Bouchard, A. Poppas, and R. Haubner Radiolabeled RGD Peptides to Image Angiogenesis in Swine Model of Hibernating Myocardium. J. Am. Coll. Cardiol. Img., January 1, 2008; 1: 500 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A R Lyon, M Sato, R J Hajjar, R J Samulski, and S E Harding Gene therapy: targeting the myocardium Heart, January 1, 2008; 94(1): 89 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Horvath and Y. Zhou Transmyocardial Laser Revascularization and Extravascular Angiogenetic Techniques to Increase Myocardial Blood Flow Card. Surg. Adult, January 1, 2008; 3(2008): 733 - 752. [Full Text]
|
|
|
|
|
|
K. Egashira, K. Nakano, K. Ohtani, K. Funakoshi, G. Zhao, Y. Ihara, J.-i. Koga, S. Kimura, R. Tominaga, and K. Sunagawa Local Delivery of Anti-Monocyte Chemoattractant Protein-1 by Gene-Eluting Stents Attenuates In-Stent Stenosis in Rabbits and Monkeys Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2563 - 2568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Iwasaki, K. Fukushima, A. Kawamoto, K. Umetani, A. Oyamada, S. Hayashi, T. Matsumoto, M. Ishikawa, T. Shibata, H. Nishimura, et al. Synchrotron Radiation Coronary Microangiography for Morphometric and Physiological Evaluation of Myocardial Neovascularization Induced by Endothelial Progenitor Cell Transplantation Arterioscler Thromb Vasc Biol, June 1, 2007; 27(6): 1326 - 1333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Saeed, D. Saloner, A. Martin, L. Do, O. Weber, P. C. Ursell, A. Jacquier, R. Lee, and C. B. Higgins Adeno-associated Viral Vector-Encoding Vascular Endothelial Growth Factor Gene: Effect on Cardiovascular MR Perfusion and Infarct Resorption Measurements in Swine Radiology, May 1, 2007; 243(2): 451 - 460. [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]
|
|
|
|
|
|
O. J. Muller, H. A. Katus, and R. Bekeredjian Targeting the heart with gene therapy-optimized gene delivery methods Cardiovasc Res, February 1, 2007; 73(3): 453 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. de Silva, L. F. Gutierrez, A. N. Raval, E. R. McVeigh, C. Ozturk, and R. J. Lederman X-Ray Fused With Magnetic Resonance Imaging (XFM) to Target Endomyocardial Injections: Validation in a Swine Model of Myocardial Infarction Circulation, November 28, 2006; 114(22): 2342 - 2350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-L. Ang, L. Takura Shenje, L. Srinivasan, and M. Galinanes Repair of the damaged heart by bone marrow cells: from experimental evidence to clinical hope. Ann. Thorac. Surg., October 1, 2006; 82(4): 1549 - 1558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. W. Zhuang, L. Gao, M. Murakami, J. D. Pearlman, T. J. Sackett, M. Simons, and E. D. de Muinck Arteriogenesis: Noninvasive Quantification with Multi-Detector Row CT Angiography and Three-dimensional Volume Rendering in Rodents Radiology, September 1, 2006; 240(3): 698 - 707. [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]
|
|
|
|
 |
|
 B. D. Wilson, M. Ii, K. W. Park, A. Suli, L. K. Sorensen, F. Larrieu-Lahargue, L. D. Urness, W. Suh, J. Asai, G. A.H. Kock, et al. Netrins Promote Developmental and Therapeutic Angiogenesis Science, August 4, 2006; 313(5787): 640 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Ripa, Y. Wang, E. Jorgensen, H. E. Johnsen, B. Hesse, and J. Kastrup Intramyocardial injection of vascular endothelial growth factor-A165 plasmid followed by granulocyte-colony stimulating factor to induce angiogenesis in patients with severe chronic ischaemic heart disease Eur. Heart J., August 1, 2006; 27(15): 1785 - 1792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Lavine, A. C. White, C. Park, C. S. Smith, K. Choi, F. Long, C.-c. Hui, and D. M. Ornitz Fibroblast growth factor signals regulate a wave of Hedgehog activation that is essential for coronary vascular development. Genes & Dev., June 15, 2006; 20(12): 1651 - 1666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. W. Sellke, R. Laham, E. J. Suuronen, and M. Ruel Angiogenesis for the treatment of inoperable coronary disease: the future. Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2006; 10(2): 184 - 188. [Abstract] [PDF]
|
|
|
|
|
|
Y Wang, H E Johnsen, S Mortensen, L Bindslev, R Sejersten Ripa, M Haack-Sorensen, E Jorgensen, W Fang, and J Kastrup Changes in circulating mesenchymal stem cells, stem cell homing factor, and vascular growth factors in patients with acute ST elevation myocardial infarction treated with primary percutaneous coronary intervention Heart, June 1, 2006; 92(6): 768 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Nordlie, L. E. Wold, B. Z. Simkhovich, C. Sesti, and R. A. Kloner Molecular Aspects of Ischemic Heart Disease: Ischemia/Reperfusion-Induced Genetic Changes and Potential Applications of Gene and RNA Interference Therapy Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2006; 11(1): 17 - 30. [Abstract] [PDF]
|
|
|
|
|
|
Y. Tsutsumi and D. W. Losordo Double Face of VEGF Circulation, August 30, 2005; 112(9): 1248 - 1250. [Full Text] [PDF]
|
|
|
|
|
|
M. Gyongyosi, A. Khorsand, S. Zamini, W. Sperker, C. Strehblow, J. Kastrup, E. Jorgensen, B. Hesse, K. Tagil, H. E. Botker, et al. NOGA-Guided Analysis of Regional Myocardial Perfusion Abnormalities Treated With Intramyocardial Injections of Plasmid Encoding Vascular Endothelial Growth Factor A-165 in Patients With Chronic Myocardial Ischemia: Subanalysis of the EUROINJECT-ONE Multicenter Double-Blind Randomized Study Circulation, August 30, 2005; 112(9_suppl): I-157 - I-165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ohtsuka, K. Inoue, Y. Hara, N. Morioka, K. Ohshima, J. Suzuki, A. Ogimoto, Y. Shigematsu, and J. Higaki Serum markers of angiogenesis and myocardial ultrasonic tissue characterization in patients with dilated cardiomyopathy Eur J Heart Fail, June 1, 2005; 7(4): 689 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kastrup, E. Jorgensen, A. Ruck, K. Tagil, D. Glogar, W. Ruzyllo, H. E. Botker, D. Dudek, V. Drvota, B. Hesse, et al. Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris: A randomized double-blind placebo-controlled study: The Euroinject One trial J. Am. Coll. Cardiol., April 5, 2005; 45(7): 982 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J Teng, K. Lachapelle, and R. C. Chiu Reappraisal of Recent Clinical Trials of Angiogenic Therapy in Myocardial Ischemia Asian Cardiovasc Thorac Ann, March 1, 2005; 13(1): 90 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R Corti, J Badimon, G Mizsei, F Macaluso, M Lee, P Licato, J F Viles-Gonzalez, V Fuster, and W Sherman Real time magnetic resonance guided endomyocardial local delivery Heart, March 1, 2005; 91(3): 348 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Davani, F. Deschaseaux, D. Chalmers, P. Tiberghien, and J.-P. Kantelip Can stem cells mend a broken heart? Cardiovasc Res, February 1, 2005; 65(2): 305 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Simoes, M. Miyagawa, S. Reder, C. Stadele, R. Haubner, W. Linke, T. Lehner, P. Epple, M. Anton, M. Schwaiger, et al. Myocardial Kinetics of Reporter Probe 124I-FIAU in Isolated Perfused Rat Hearts After In Vivo Adenoviral Transfer of Herpes Simplex Virus Type 1 Thymidine Kinase Reporter Gene J. Nucl. Med., January 1, 2005; 46(1): 98 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ohtani, K. Egashira, K.-i. Hiasa, Q. Zhao, S. Kitamoto, M. Ishibashi, M. Usui, S. Inoue, Y. Yonemitsu, K. Sueishi, et al. Blockade of Vascular Endothelial Growth Factor Suppresses Experimental Restenosis After Intraluminal Injury by Inhibiting Recruitment of Monocyte Lineage Cells Circulation, October 19, 2004; 110(16): 2444 - 2452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kawamoto, T. Murayama, K. Kusano, M. Ii, T. Tkebuchava, S. Shintani, A. Iwakura, I. Johnson, P. von Samson, A. Hanley, et al. Synergistic Effect of Bone Marrow Mobilization and Vascular Endothelial Growth Factor-2 Gene Therapy in Myocardial Ischemia Circulation, September 14, 2004; 110(11): 1398 - 1405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.M Rubanyi The design and preclinical testing of Ad5FGF-4 to treat chronic myocardial ischaemia Eur. Heart J. Suppl., September 1, 2004; 6(suppl_E): E12 - E17. [Abstract] [Full Text]
|
|
|
|
|
|
L.G Melo, M Gnecchi, A.S Pachori, K Wang, and V.J Dzau Gene- and cell-based therapies for cardiovascular diseases: current status and future directions Eur. Heart J. Suppl., September 1, 2004; 6(suppl_E): E24 - E35. [Abstract] [Full Text]
|
|
|
|
|
|
V. van Weel, M. M.L. Deckers, J. M. Grimbergen, K. J.M. van Leuven, J. H.P. Lardenoye, R. O. Schlingemann, G. P. van Nieuw Amerongen, J. H. van Bockel, V. W.M. van Hinsbergh, and P. H.A. Quax Vascular Endothelial Growth Factor Overexpression in Ischemic Skeletal Muscle Enhances Myoglobin Expression In Vivo Circ. Res., July 9, 2004; 95(1): 58 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Losordo and S. Dimmeler Therapeutic Angiogenesis and Vasculogenesis for Ischemic Disease: Part I: Angiogenic Cytokines Circulation, June 1, 2004; 109(21): 2487 - 2491. [Full Text] [PDF]
|
|
|
|
|
|
L. G. Melo, A. S. Pachori, D. Kong, M. Gnecchi, K. Wang, R. E. Pratt, and V. J. Dzau Molecular and Cell-Based Therapies for Protection, Rescue, and Repair of Ischemic Myocardium: Reasons for Cautious Optimism Circulation, May 25, 2004; 109(20): 2386 - 2393. [Full Text] [PDF]
|
|
|
|
|
|
N. Svorkdal Treatment of Inoperable Coronary Disease and Refractory Angina: Spinal Stimulators, Epidurals, Gene Therapy, Transmyocardial Laser, and Counterpulsation Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2004; 8(1): 43 - 58. [Abstract] [PDF]
|
|
|
|
|
|
R. Kirchmair, R. Gander, M. Egger, A. Hanley, M. Silver, A. Ritsch, T. Murayama, N. Kaneider, W. Sturm, M. Kearny, et al. The Neuropeptide Secretoneurin Acts as a Direct Angiogenic Cytokine In Vitro and In Vivo Circulation, February 17, 2004; 109(6): 777 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Pels, C. Deiner, S. E Coupland, M. Noutsias, A. P Sutter, H.-P. Schultheiss, S. Yla-Herttuala, and P. L Schwimmbeck Effect of adventitial VEGF165 gene transfer on vascular thickening after coronary artery balloon injury Cardiovasc Res, December 1, 2003; 60(3): 664 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. P. Fam, S. Verma, M. Kutryk, and D. J. Stewart Clinician Guide to Angiogenesis Circulation, November 25, 2003; 108(21): 2613 - 2618. [Full Text] [PDF]
|
|
|
|
 |
|
 C. A.U. Heilmann, T. Attmann, A. Thiem, E. Haffner, F. Beyersdorf, and G. Lutter Gene therapy in cardiac surgery: intramyocardial injection of naked plasmid DNA for chronic myocardial ischemia Eur. J. Cardiothorac. Surg., November 1, 2003; 24(5): 785 - 793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Russell and K.-W. Peng Primer on Medical Genomics Part X: Gene Therapy Mayo Clin. Proc., November 1, 2003; 78(11): 1370 - 1383. [Abstract] [PDF]
|
|
|
|
|
|
F. M. Bengel, M. Anton, T. Richter, M. V. Simoes, R. Haubner, J. Henke, W. Erhardt, S. Reder, T. Lehner, W. Brandau, et al. Noninvasive Imaging of Transgene Expression by Use of Positron Emission Tomography in a Pig Model of Myocardial Gene Transfer Circulation, October 28, 2003; 108(17): 2127 - 2133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-s. Yoon and D. W. Losordo All in the Family: VEGF-B Joins the Ranks of Proangiogenic Cytokines Circ. Res., July 25, 2003; 93(2): 87 - 90. [Full Text] [PDF]
|
|
|
|
|
|
C. A. Thompson, B. A. Nasseri, J. Makower, S. Houser, M. McGarry, T. Lamson, I. Pomerantseva, J. Y. Chang, H. K. Gold, J. P. Vacanti, et al. Percutaneous transvenous cellular cardiomyoplasty: A novel nonsurgical approach for myocardial cell transplantation J. Am. Coll. Cardiol., June 4, 2003; 41(11): 1964 - 1971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fuchs, L. F. Satler, R. Kornowski, P. Okubagzi, G. Weisz, R. Baffour, R. Waksman, N. J. Weissman, M. Cerqueira, M. B. Leon, et al. Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: A feasibility study J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1721 - 1724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. Henry, B. H. Annex, G. R. McKendall, M. A. Azrin, J. J. Lopez, F. J. Giordano, P.K. Shah, J. T. Willerson, R. L. Benza, D. S. Berman, et al. The VIVA Trial: Vascular Endothelial Growth Factor in Ischemia for Vascular Angiogenesis Circulation, March 18, 2003; 107(10): 1359 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Strauer and R. Kornowski Stem Cell Therapy in Perspective Circulation, February 25, 2003; 107(7): 929 - 934. [Full Text] [PDF]
|
|
|
|
|
|
E. C. Perin, Y.-J. Geng, and J. T. Willerson Adult Stem Cell Therapy in Perspective Circulation, February 25, 2003; 107(7): 935 - 938. [Full Text] [PDF]
|
|
|
|
|
|
F. W. Sellke and M. Ruel Vascular growth factors and angiogenesis in cardiac surgery Ann. Thorac. Surg., February 1, 2003; 75(2): S685 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ruel, R. A. Kelly, and F. W. Sellke Therapeutic Angiogenesis, Transmyocardial Laser Revascularization, and Cell Therapy Card. Surg. Adult, January 1, 2003; 2(2003): 715 - 750. [Full Text]
|
|
|
|
|
|
Z. He, C. Rask-Madsen, and G.L. King Mechanisms of cardiovascular complications in diabetes and potential new pharmacological therapies Eur. Heart J. Suppl., January 1, 2003; 5(suppl_B): B51 - B57. [Abstract] [PDF]
|
|
|
|
|
|
D. W. Losordo and A. Kawamoto Biological Revascularization and the Interventional Molecular Cardiologist: Bypass for the Next Generation Circulation, December 10, 2002; 106(24): 3002 - 3005. [Full Text] [PDF]
|
|
|
|
|
|
H. Kamihata, H. Matsubara, T. Nishiue, S. Fujiyama, K. Amano, O. Iba, T. Imada, and T. Iwasaka Improvement of Collateral Perfusion and Regional Function by Implantation of Peripheral Blood Mononuclear Cells Into Ischemic Hibernating Myocardium Arterioscler Thromb Vasc Biol, November 1, 2002; 22(11): 1804 - 1810. [Abstract] [Full Text] [PDF]
|
|