Affiliation:
1. From INSERM EMI-0016, Necker-Paris V University and Department of Cardiology 1, Hôpital Européen Georges Pompidou (S.G., A.A.H.); Department of Cardiovascular Surgery B, Hôpital Bichat (L.C.G.S., B.P., P.M.); INSERM U523, Institut de Myologie, Pitié Salpétrière (C.C., J.T.V., K.S.); INSERM 430, Hôpital Broussais (P.B.); and eDepartment of Cardiology, Hôpital Cochin (P.R.), Paris, France.
Abstract
Background
Transplantation (Tx) of skeletal myoblasts (SM) within an infarcted myocardium improves global left ventricular (LV) function, although a direct systolic effect remains controversial.
Methods and Results
Global and regional LV functions were studied in a sheep model (n=16) of infarction before (baseline), and 4 (M4), and 12 (M12) months after in-scar injections of autologous SM or culture medium (CM). LV end-diastolic volume (EDV), ejection fraction (EF), wall motion score (WMS), and systolic myocardial velocity gradient (MVG) across the scar were measured by echocardiography with tissue Doppler imaging. Parameters were similar at baseline between groups. At M4, Tx of SM reduced the postinfarction increase in EDV (72±8 versus 105±13 mL in the CM group,
P
<0.05) and the decrease in EF (48±5 versus 33±3% in the CM group,
P
=0.006) although it improved WMS (5.4±1.2 versus 13±2.2 in the CM group,
P
<0.01) and SMVG (0.60±0.13 versus –0.04±.13 seconds
-1
in the CM group,
P
<0.05). Results were similar at M12. In-scar accumulation of myotubes and SM were detected in all Tx animals up to M12, with co-expression of fast and slow isoforms of the myosin heavy chain (MHC) (30% of the fibers versus 0% in the normal skeletal muscle) and decreased collagen density (30±2% versus 73±3%,
P
<0.0001).
Conclusion
For up to 1 year, Tx of SM limits postinfarction EF deterioration and improves systolic scar function through colonization of fibrosis by skeletal muscle cells with expression of both MHC isoforms, which may confer to the graft the ability to withstand a cardiac-type workload.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
203 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献