Copyright © 2005, European Society of Cardiology
Autologous myoblast transplantation after myocardial infarction increases the inducibility of ventricular arrhythmias
L'Institut du Thorax INSERM U533, Faculté de Médecine, Nantes, France
PIMESP, CHU Nantes, France
INSERM U652, Paris
Service de Biochimie, CHU Nantes, France
Service d'Anatomo-pathologie, CHU Nantes, France
* Corresponding author. L'Institut du Thorax INSERM U533, Faculté de Médecine, 1 rue Gaston Veil, F-44035 Nantes cedex 1, France. Tel.: +33 2 40 41 29 91; fax: +33 2 40 41 29 50. Email address: patricia.lemarchand{at}nantes.inserm.fr
Background: Small scale clinical trials suggested the feasibility and the efficacy of autologous myoblast transplantation to improve ventricular function after myocardial infarction. However, these trials were hampered by unexpected episodes of life-threatening ventricular tachyarrhythmias (VT). We investigated cardiac electrical stability after myoblast transplantation to the myocardium.
Methods and results: Seven days after coronary ligation, Wistar rats were randomized into 3 groups: a control group receiving no further treatment, a vehicle group injected with culture medium into the infarcted myocardium, and a myoblast group injected with autologous myoblasts. Holter monitoring did not discriminate the myoblast from the vehicle groups. Programmed Electrical Stimulation (PES) was performed to evaluate further a cardiac substrate for arrhythmia susceptibility. The occurrence of sustained VT during PES was similar in control and vehicle groups (5/17 and 4/19 rats, respectively; p=0.50). In contrast, 13/20 rats (65%) from the myoblast group showed at least one episode of sustained VT during PES (p<0.05 and p<0.005 versus control and vehicle groups). As a further control group, rats injected with autologous bone marrow mononuclear cells into the infarcted myocardium did not show increased susceptibility to PES.
Conclusions: In an infarcted rat model, myoblast transplantation but not bone marrow mononuclear cells or myocardial injection per se induces electrical ventricular instability. Because ventricular arrhythmias are life-threatening disorders, we suggest that such preclinical evaluation should be conducted for any new source of cells to be injected into the myocardium.
Time for primary review 21 days
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