Autologous myoblast transplantation after myocardial infarction increases the inducibility of ventricular arrhythmias

Unité Inserm U1077, Caen, Lower Normandy, France
Cardiovascular Research (Impact Factor: 5.94). 03/2006; 69(2):348-58. DOI: 10.1016/j.cardiores.2005.10.003
Source: PubMed


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.
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.
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.

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Available from: Patricia Lemarchand, Dec 25, 2013
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    • "Seven days after MI induction, BM-MNCs were quickly thawed and labeled immediately before injection using a green intracellular fluorescent dye, Carboxy Fluorescein diacetate Succinimidyl Ester (CFSE, Molecular Probes Invitrogen, Cergy Pontoise, France) [7]. "
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    • "In addition, obtaining the therapeutic quantity of these cells requires general anesthesia and hospitalization. A study using autologous skeletal myocytes showed clear benefit, but also showed concerns of arrhythmia.21-23 "
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    • "The two episodes of spontaneous ventricular tachycardia were detected in the early period after transplant, a finding which is consistent with recent studies [41]. It is possible that SkM transplant may increase the susceptibility to arrhythmia, as has been recently suggested using Programmed Electric Stimulation [42]. "
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