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 Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ghostine, S. Articles by Hagège, A. A. Search for Related Content PubMed PubMed Citation Articles by Ghostine, S. Articles by Hagège, A. A. Related Collections Chronic ischemic heart disease Echocardiography CV surgery: transplantation, ventricular assistance, cardiomyopathy Myogenesis

(Circulation. 2002;106:I-131.)
© 2002 American Heart Association, Inc.

Thoracic Transplantation and Mechanical Support for Congestive Heart Failure

Long-Term Efficacy of Myoblast Transplantation on Regional Structure and Function After Myocardial Infarction

Saïd Ghostine, MD; Claire Carrion, MSc; Luiz César Guarita Souza, MD; Pascal Richard, MD; Patrick Bruneval, MD; Jean-Thomas Vilquin, PhD; Bruno Pouzet, MD; Ketty Schwartz, PhD; Philippe Menasché, MD, PhD; Albert Alain Hagège, MD, PhD

From INSERM EMI-0016, Necker-Paris V University and Department of Cardiology 1, Hôpital Européen Georges Pompidou (S.G., A.A.H.); Department of Cardiovascular Surgery B, Hôpital Bichat (L.C.G.S., B.P., P.M.); INSERM U523, Institut de Myologie, Pitié Salpétrière (C.C., J.T.V., K.S.); INSERM 430, Hôpital Broussais (P.B.); and ^eDepartment of Cardiology, Hôpital Cochin (P.R.), Paris, France.

Correspondence to Albert Alain Hagège, MD, PhD, Department of Cardiology 1, Hôpital Européen Georges Pompidou, 20 Rue Leblanc, 75015 Paris. E-mail hagege{at}club-internet.fr

Abstract

Background Transplantation (Tx) of skeletal myoblasts (SM) within an infarcted myocardium improves global left ventricular (LV) function, although a direct systolic effect remains controversial.

Methods and Results Global and regional LV functions were studied in a sheep model (n=16) of infarction before (baseline), and 4 (M4), and 12 (M12) months after in-scar injections of autologous SM or culture medium (CM). LV end-diastolic volume (EDV), ejection fraction (EF), wall motion score (WMS), and systolic myocardial velocity gradient (MVG) across the scar were measured by echocardiography with tissue Doppler imaging. Parameters were similar at baseline between groups. At M4, Tx of SM reduced the postinfarction increase in EDV (72±8 versus 105±13 mL in the CM group, P<0.05) and the decrease in EF (48±5 versus 33±3% in the CM group, P=0.006) although it improved WMS (5.4±1.2 versus 13±2.2 in the CM group, P<0.01) and SMVG (0.60±0.13 versus –0.04±.13 seconds^-1 in the CM group, P<0.05). Results were similar at M12. In-scar accumulation of myotubes and SM were detected in all Tx animals up to M12, with co-expression of fast and slow isoforms of the myosin heavy chain (MHC) (30% of the fibers versus 0% in the normal skeletal muscle) and decreased collagen density (30±2% versus 73±3%, P<0.0001).

Conclusion For up to 1 year, Tx of SM limits postinfarction EF deterioration and improves systolic scar function through colonization of fibrosis by skeletal muscle cells with expression of both MHC isoforms, which may confer to the graft the ability to withstand a cardiac-type workload.

Key Words: transplantation • skeletal myoblasts • cell therapy • myocardial infarction

This article has been cited by other articles:

				M. S. Lee and R. R. Makkar Stem-Cell Transplantation in Myocardial Infarction: A Status Report Ann Intern Med, May 4, 2004; 140(9): 729 - 737. [Abstract] [Full Text] [PDF]