Skeletal myoblast implants induce minor propagation delays, but do not promote arrhythmias in the normal swine heart.
OBJECTIVE
Whether skeletal myoblast (SM) implants are proarrhythmic is still controversial due to conflicting pre-clinical and clinical data. We hypothesized that if SM implants are arrhythmogenic, they will facilitate the induction of ventricular tachyarrhythmias by promoting heterogeneous propagation of activation wavefronts.


METHODS
Skeletal myoblast cells were harvested from 10 pigs. A month later, 125 ± 37 × 10(6) cells were subepicardially injected in an area of ∼2 cm(2) at the anterolateral aspect of the left ventricle. Four weeks later, a ventricular stimulation protocol was conducted. Once explanted, epicardial wavefronts over SM and adjacent control areas were optically mapped. Eight saline-injected animals were used as controls. To compare with clear arrhythmogenic substrates, propagation patterns were also evaluated in infarcted hearts and on a SM-implanted heart following amiodarone infusion.


RESULTS
In SM hearts, fibrosis and differentiated SM cells were consistently found and no tachyarrhythmias were induced. Wavefronts propagated homogeneously over SM and adjacent areas, with no late activation zones, as opposed to the infarcted hearts. The time required for the wavefronts to depolarize both areas were similar, becoming only slightly longer at SM areas after an extra-stimulus (P = 0.025). Conduction velocities and APD(90) were also similar. Saline hearts showed similar results. The extent of the conduction delay was not related to the number of injected SM cells.


CONCLUSIONS
In normal swine hearts, myoblast implants promote localized fibrosis and slightly retard epicardial wavefront propagation only after extra-stimuli. However, SM implants are not associated with local re-entry and do not facilitate ventricular tachyarrhythmias in the whole normal heart.
Moreno
Javier
J
Optical Mapping Laboratory, Arrhythmia Unit and Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain. jmoreno@secardiologia.es
Quintanilla
Jorge G
JG
López-Farré
Antonio
A
Archondo
Tamara
T
Cervigón
Raquel
R
Aragoncillo
Paloma
P
Usandizaga
Elena
E
Silva
Jacobo
J
Rodríguez-Bobada
Cruz
C
Rojo
José Luis
JL
Pérez-Castellano
Nicasio
N
Mironov
Sergey
S
Mont
Lluis
L
Pérez de Prada
Teresa
T
Macaya
Carlos
C
Pérez-Villacastín
Julián
J
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000638:Amiodarone / Q000494:pharmacology; D000818:Animals; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology*; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000637:transplantation*; D009203:Myocardial Infarction / Q000503:physiopathology / Q000601:surgery*; D013552:Swine; D013610:Tachycardia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*
D000638:Amiodarone