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(Circulation. 2001;104:I-223.)
© 2001 American Heart Association, Inc.

Thoracic Transplantation and Ventricular Assist Devices

Is Skeletal Myoblast Transplantation Clinically Relevant in the Era of Angiotensin-Converting Enzyme Inhibitors?

Bruno Pouzet, MD; Saïd Ghostine, MD; Jean-Thomas Vilquin, PhD; Isabelle Garcin, MSc; Marcio Scorsin, MD, PhD; Albert A. Hagège, MD, PhD; Denis Duboc, MD; Ketty Schwartz, PhD; Philippe Menasché, MD, PhD

Service de Chirurgie Cardiovasculaire B, Groupe Hospitalier Bichat-Claude Bernard, Paris, France (B.P., M.S., P.M.); Service de Cardiologie 3, Hôpital Européen Georges Pompidou, and Faculté Necker-Enfants Malades, Paris V, France (S.G., A.A.H.); INSERM U523, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France (B.P., J.-T.V., I.G., K.S.); and Service de Cardiologie, Hôpital Cochin, Paris, France (D.D.).

Correspondence to Dr Philippe Menasché, Service de Chirurgie Cardiovasculaire B, Groupe Hospitalier Bichat-Claude Bernard, 46, rue Henri Huchard, 75877 Paris Cedex 18, France. E-mail ccv-bloc.sec3{at}bch.ap-hop-paris.fr

Background— There is compelling experimental evidence that autologous skeletal muscle (SM) cell transplantation improves postinfarction cardiac function. This study assessed whether this benefit is still manifested in the clinically relevant setting of a treatment by ACE inhibitors.

Methods and Results— A myocardial infarction was created in 99 rats by coronary artery ligation. They were divided into 4 groups. Two groups did not receive any drug and were intramyocardially injected 7 days after the infarct with either culture medium alone (control rats, n=16) or autologous SM cells (2.3x10⁶ myoblasts) previously expanded ex vivo for 7 days (myoblasts, n=24). Two other groups received the ACE inhibitor perindoprilat (1 mg · kg^-1 · d^-1), started the day of the infarct and continued uninterruptedly thereafter, and underwent time-matched procedures, that is, they were intramyocardially injected at 7 days after infarction with either culture medium alone (ACE inhibitors, n=22) or autologous SM cells (2.5x10⁶ myoblasts) previously expanded ex vivo for 7 days (ACE inhibitors+myoblasts, n=37). Left ventricular function was assessed by 2D echocardiography. At the end of the 2-month study, left ventricular ejection fraction (%, mean±SEM) was increased in all groups (myoblasts, 37.4±1.2; ACE inhibitors, 31.6±1.7; ACE inhibitors+myoblasts, 43.9±1.4) compared with that in control rats (19.8±0.7) (P<0.0001). The improvement in ejection fraction was similar in the ACE inhibitor and the myoblast groups (31.6±1.7 versus 37.4±1.2, P=0.0636). However, in the ACE inhibitor+myoblast group, this improvement was greater than that seen in hearts receiving either treatment alone (43.9±1.4 versus 31.6±1.7 in the ACE inhibitor group and 43.9±1.4. versus 37.4±1.2 in the myoblast group, P<0.0001 and P=0.0084, respectively).

Conclusions— These data provide further support for the clinical relevance of autologous SM cell transplantation in that its cardioprotective effects are additive to those observed with ACE inhibitors.

Key Words: heart failure • muscles • transplantation • myocardial infarction • angiotensin