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(Hypertension. 2001;38:1413.)
© 2001 American Heart Association, Inc.

Fourth International Seminar on Cardiovascular Biology and Medicine: Part II

Regeneration of the Myocardium

A New Role in the Treatment of Ischemic Heart Disease?

Albert A. Hagège; Jean-Thomas Vilquin; Patrick Bruneval; Philippe Menasché

From the Faculté de Médecine Necker, Paris V University (A.A.H.) and the Department of Cardiology (A.A.H.), Hôpital Européen Georges Pompidou; INSERM U523, Institut de Myologie, Groupe Hospitalier Pitié-Salpétrière (J.-T.V.); INSERM U430, Hôpital Broussais (P.B.); and the Department of Cardiovascular Surgery, Hôpital Bichat (P.M.), Paris, France.

Correspondence to Albert A. Hagège, MD, PhD, Department of Cardiology, Hôpital Européen Georges Pompidou, Paris, France. E-mail hagege{at}club-internet.fr

Abstract

Intramyocardial cell grafting aims to limit the consequences of the loss of contractile function of a damaged left ventricle. Its functional efficacy is suggested by a wealth of experimental data using multiple evaluation techniques in different animal species. Intramyocardial injections of cultured fetal cardiomyocytes after infarction increase the ejection fraction. Cultured autologous skeletal myoblasts, which do not raise immunologic, ethical, tumorigenesis, or donor availability problems, improve ventricular function to a similar extent. The presence of connexin-43 is demonstrated between fetal (but not myoblast) grafted cells and host myocytes. Thus, the mechanisms of this beneficial effect (direct systolic effect, paracrine factors, passive girdling effect, and decrease in wall stress) remain controversial. These encouraging results have opened the way to the first clinical trial in patients with low ejection fractions, akinetic and nonviable postinfarction scars, and indications for coronary artery bypasses in remote, viable, and ischemic areas. Large-scale cell expansion allows a yield of >10⁹ myoblasts from a single human muscular biopsy. Cultured autologous myoblasts are directly administered by multiple injections within and around the infarcted area during open-chest surgery. Preliminary postoperative observations show an improvement in ejection fraction, reappearance of a systolic thickening of the grafted scars, and a new-onset metabolic viability within this area. Thus, this new procedure might become a useful adjunct to current treatments of severe ischemic heart failure.

Key Words: myocytes • transplantation • myocardial infarction • heart failure • myocardium

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