Le site du Docteur Miguel-Angel CORTES-MORICHETTI

Cardiologie
Conventionnement : Secteur 1

The Journal of Thoracic and Cardiovascular Surgery c October 2009 New article

New article October 2009 The Journal of Thoracic and Cardiovascular Surgery c October 2009 Association of electrostimulation with cell transplantation in ischemic heart disease Abdel Shafy, MD,a Thomas Lavergne, MD,b Christian Latremouille, MD, PhD,a Miguel Cortes-Morichetti, MD,b Alain Carpentier, MD, PhD,a and Juan C. Chachques, MD, PhDa Background: Until now, cell therapy has constituted a passive therapeutic approach; the only effects seem to be related to the reduction of the myocardial fibrosis and the limitation of the adverse ventricular remodeling. Cardiac resynchronization therapy is indicated in patients with heart failure to correct conduction disorders associated with chronic systolic and diastolic dysfunction. The association of electrostimulation with cellular cardiomyoplasty could be a way to transform passive cell therapy into ‘‘dynamic cellular support.’’ Electrostimulation of ventricles following skeletal myoblast implantation should induce the contraction of the transplanted cells and a higher expression of slow myosin, which is better adapted for chronic ventricular assistance. The purpose of this study is to evaluate myogenic cell transplantation in an ischemic heart model associated with cardiac resynchronization therapy. Methods: Twenty two sheep were included. All animals underwent myocardial infarction by ligation of 2 coronary artery branches (distal left anterior descending artery and D2). After 4 weeks, autologous cultured myoblasts were injected in the infarcted areas with or without pacemaker implantation. Atrial synchronized biventricular pacing was performed using epicardial electrodes. Echocardiography was performed at 4 weeks (baseline) and 12 weeks after infarction. Results: Echocardiography showed a significant improvement in ejection fraction and limitation of left ventricular dilatation in cell therapy with cardiac resynchronization therapy as compared with the other groups. Viable cells were identified in the infarcted areas. Differentiation of myoblasts into myotubes and enhanced expression of slow myosin heavy chain was observed in the electrostimulated group. Transplantation of cells with cardiac resynchronization therapy caused an increase in diastolic wall thickening in the infarcted zone relative to cells-only group and cardiac resynchronization therapy–only group. Conclusions: Biventricular pacing seems to induce synchronous contraction of transplanted myoblasts and the host myocardium, thus improving ventricular function. Electrostimulation was related with enhanced expression of slow myosin and the organization of myoblasts in myotubes, which are better adapted at performing cardiac work. Patients with heart failure presenting myocardial infarct scars and indication for cardiac resynchronization therapy might benefit from simultaneous cardiac pacing and cell therapy. Cell transplantation for cardiac support and regeneration may repair the injured heart but is limited by poor effect in systolic function. This can be due to the lack of gap junctions between the native myocardium and the grafted cells. Also, cell transplantation seems to be limited by death of transplanted cells.1-4 Most cell death occurs in the first few days posttransplantation, likely from a combination of ischemia, anoikis, and inflammation. Anoikis is a form of apoptosis that is induced by anchorage-dependent cells detaching from the surrounding extracellular matrix. Interventions known to enhance transplanted cell survival include heat shock, overexpressing antiapoptotic proteins, free radical scavengers, anti-inflammatory therapy, and codelivery of extracellular matrix molecules. Combinatorial use of such interventions could enhance graft cell survival.5 Despite these possibilities, until now cell transplantation has constituted a passive therapeutic approach; the only effects seem to be related to the reduction of the myocardial fibrosis and the limitation of the adverse ventricular remodeling. 6,7 Atrial synchronized biventricular pacing for cardiac resynchronization therapy (CRT) is indicated in patients with heart failure to correct conduction disorders associated with chronic systolic and diastolic dysfunction.8-10 The association of electrostimulation with cellular cardiomyoplasty could be a way to transform passive cell therapy

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