HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Carolyn J. Teng Jun Luo Dominique Shum-Tim Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Teng, C. J. Articles by Shum-Tim, D. Search for Related Content PubMed PubMed Citation Articles by Teng, C. J. Articles by Shum-Tim, D. Related Collections Cardiac - physiology Congestive Heart Failure Transplantation - heart

J Thorac Cardiovasc Surg 2006;132:628-632
© 2006 The American Association for Thoracic Surgery

Evolving Technology

Massive mechanical loss of microspheres with direct intramyocardial injection in the beating heart: Implications for cellular cardiomyoplasty

Division of Cardiac Surgery, McGill University, Montreal, Quebec, Canada.

Presented in part at the Annual Congress of The American Heart Association, Dallas, Tex, Nov 14, 2005.

Received for publication December 8, 2005; revisions received April 11, 2006; accepted for publication May 24, 2006.

^_* Address for reprints: Dominique Shum-Tim, MD, Division of Cardiac Surgery, The Montreal General Hospital, MUHC, 1650 Cedar Ave, Suite C9-169, Montreal, Quebec, Canada H3G 1A4 (Email: dshumtim{at}yahoo.ca).

OBJECTIVE: Direct intramyocardial injection is a common route of donor cell administration for myocardial cell therapy. Studies have demonstrated a significant and rapid loss of implanted cells, which is thought to be biologically caused. We hypothesized that mechanical loss of cells from the contracting myocardium might actually be the main culprit.

METHODS: Intramyocardial injections of fluorescent microspheres (10 µm) were carried out in both small and large animal models. The hearts of Lewis rats (250-350 g) received 3 x 10⁶ microspheres injected into the left ventricular myocardium. Rats were divided evenly between two experienced operators. The nonbeating (n = 2) and beating (n = 5) hearts of piglets (7.5-7.8 kg) received 3 x 10⁶ microspheres. The hearts were excised within 10 minutes, and the microspheres retained in the myocardium were quantified with fluorescent flow cytometry.

RESULTS: In the beating-heart rat model, the microsphere retention rates after a single injection were similar with and without purse-string occlusion of needle puncture sites and slightly lower than after multiple site injections (6.19% ± 4.05% vs 5.44% ± 5.66% vs 8.83% ± 3.29%). There were no significant operator-dependent differences. The retention rates in beating porcine hearts were higher than those in the rats (P < .05) but markedly lower than those in nonbeating porcine hearts (11.1% vs 67.4%).

CONCLUSION: Mechanical leakage and washout may account for a major portion of cell loss after cell implantation, and efforts aimed at reducing mechanical loss in the beating heart may yield a greater benefit than those targeting biologic loss alone.

This article has been cited by other articles:

				P. Menasche, O. Alfieri, S. Janssens, W. McKenna, H. Reichenspurner, L. Trinquart, J.-T. Vilquin, J.-P. Marolleau, B. Seymour, J. Larghero, et al. The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: First Randomized Placebo-Controlled Study of Myoblast Transplantation Circulation, March 4, 2008; 117(9): 1189 - 1200. [Abstract] [Full Text] [PDF]

				J. C. Chachques, J. C. Trainini, N. Lago, M. Cortes-Morichetti, O. Schussler, and A. Carpentier Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM Trial): Clinical Feasibility Study Ann. Thorac. Surg., March 1, 2008; 85(3): 901 - 908. [Abstract] [Full Text] [PDF]

				R. Atoui, J.-F. Asenjo, M. Duong, G. Chen, R. C.-J. Chiu, and D. Shum-Tim Marrow Stromal Cells as Universal Donor Cells for Myocardial Regenerative Therapy: Their Unique Immune Tolerance Ann. Thorac. Surg., February 1, 2008; 85(2): 571 - 579. [Abstract] [Full Text] [PDF]

				C.-C. Wang, C.-H. Chen, W.-W. Lin, S.-M. Hwang, P. C.H. Hsieh, P.-H. Lai, Y.-C. Yeh, Y. Chang, and H.-W. Sung Direct intramyocardial injection of mesenchymal stem cell sheet fragments improves cardiac functions after infarction Cardiovasc Res, February 1, 2008; 77(3): 515 - 524. [Abstract] [Full Text] [PDF]

				H. Zhang, P. Song, Y. Tang, X.-l. Zhang, S.-h. Zhao, Y.-j. Wei, and S.-s. Hu Injection of bone marrow mesenchymal stem cells in the borderline area of infarcted myocardium: heart status and cell distribution. J. Thorac. Cardiovasc. Surg., November 1, 2007; 134(5): 1234 - 1240. [Abstract] [Full Text] [PDF]

				C. Guo, H. Kh. Haider, W. S.N. Shim, R.-S. Tan, L. Ye, S. Jiang, P. K. Law, P. Wong, and E. K.W. Sim Myoblast-based cardiac repair: xenomyoblast versus allomyoblast transplantation. J. Thorac. Cardiovasc. Surg., November 1, 2007; 134(5): 1332 - 1339. [Abstract] [Full Text] [PDF]

				A. Tomescot, J. Leschik, V. Bellamy, G. Dubois, E. Messas, P. Bruneval, M. Desnos, A. A. Hagege, M. Amit, J. Itskovitz, et al. Differentiation In Vivo of Cardiac Committed Human Embryonic Stem Cells in Postmyocardial Infarcted Rats Stem Cells, September 1, 2007; 25(9): 2200 - 2205. [Abstract] [Full Text] [PDF]

				J. Nussbaum, E. Minami, M. A. Laflamme, J. A. I. Virag, C. B. Ware, A. Masino, V. Muskheli, L. Pabon, H. Reinecke, and C. E. Murry Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response FASEB J, May 1, 2007; 21(7): 1345 - 1357. [Abstract] [Full Text] [PDF]