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European Heart Journal Advance Access published online on February 23, 2005
European Heart Journal, doi:10.1093/eurheartj/ehi151
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European Heart Journal © The European Society of Cardiology 2005; all rights reserved

Preclinical research

Skeletal myoblast transplantation through a catheter-based coronary sinus approach: an effective means of improving function of infarcted myocardium

Camille Brasselet 1*, Miguel Cortes Morichetti 2, Emmanuel Messas 3, Claire Carrion 4, Alvine Bissery 5, Patrick Bruneval 6, Jean-Thomas Vilquin 4, Antoine Lafont 7, Albert A. Hagège 3, Philippe Menasché 8, and Michel Desnos 3

1 Assistance Publique-Hôpitaux de Paris, Department of Cardiology, Hôpital Européen Georges Pompidou et Faculté de Médecine René Descartes, Université Paris V, Paris, France; Department of Cardiology, CHU Robert Debré, Avenue du général Koenig, 51092 Reims Cedex, France; INSERM U 633 and Ecole de Chirurgie de l'Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM EMI 0016, Faculté Necker, Paris, France
2 INSERM U 633 and Ecole de Chirurgie de l'Assistance Publique-Hôpitaux de Paris, Paris, France
3 Assistance Publique-Hôpitaux de Paris, Department of Cardiology, Hôpital Européen Georges Pompidou et Faculté de Médecine René Descartes, Université Paris V, Paris, France; INSERM U 633 and Ecole de Chirurgie de l'Assistance Publique-Hôpitaux de Paris, Paris, France
4 INSERM U 582, Institut de Myologie, Groupe Hospitalier Pitié-Salpétrière, Paris, France
5 Clinical Investigations Center 9201-INSERM, Hôpital Européen Georges Pompidou, Paris, France
6 Department of Pathology and INSERM U 430, Hôpital Européen Georges Pompidou et Faculté de Médecine René Descartes, Université Paris V, Paris, France
7 Assistance Publique-Hôpitaux de Paris, Department of Cardiology, Hôpital Européen Georges Pompidou et Faculté de Médecine René Descartes, Université Paris V, Paris, France; INSERM EMI 0016, Faculté Necker, Paris, France
8 INSERM U 633 and Ecole de Chirurgie de l'Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou et Faculté de Médecine René Descartes, Université Paris V, Paris, France

* To whom correspondence should be addressed.
Camille Brasselet, E-mail: camille.brasselet{at}wanadoo.fr


  Abstract

Aims This study was designed to assess the functional effects of a transvenous coronary sinus technique of skeletal myoblast delivery in infarcted myocardium.

Methods and results An anterior myocardial infarction was created percutaneously in 14 sheep. Simultaneously, a muscle biopsy was harvested and expanded. Two weeks later, sheep were instrumented percutaneously with a dedicated catheter incorporating an extendable needle for puncture of the venous wall and, under endovascular ultrasound guidance, a microcatheter was advanced through the needle into the target scar for cell delivery. Following the baseline echocardiographic assessment of left ventricular (LV) function, sheep were randomly allocated to receive four-staged in-scar injections of either autologous cells (n = 7) or culture medium (n = 7). Two months later, LV function was reassessed blindly and hearts were explanted for subsequent histological and immunohistochemical analysis. There were no acute procedural complications. Baseline LV ejection fraction (EF) was significantly lower in transplanted sheep than in controls [38% (35-48) vs. 51% (38-55), respectively, P = 0.03; median (range)]. Two months later, LVEF was significantly higher in the transplanted group than in controls [50% (47-56) vs. 39% (36-47), respectively, P = 0.002]. Clusters of myoblasts were identified by histology and immunohistochemistry in three of the seven transplanted sheep.

Conclusion These data suggest the functional efficacy of the transvenous coronary sinus technique as a less invasive means of cell delivery to infarcted myocardium.

Keywords: Cell therapy; Skeletal myoblasts; Transplantation; Myocardial infarction; Percutaneous intervention.
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