title: Skeletal myoblast implants induce minor propagation delays, but do not promote arrhythmias in the normal swine heart.
abstract: 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.
authors.affiliation: Optical Mapping Laboratory, Arrhythmia Unit and Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain. jmoreno@secardiologia.es
authors.forename: Javier
authors.initials: J
authors.lastname: Moreno
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Quintanilla
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Farré
authors.forename: Tamara
authors.initials: T
authors.lastname: Archondo
authors.forename: Raquel
authors.initials: R
authors.lastname: Cervigón
authors.forename: Paloma
authors.initials: P
authors.lastname: Aragoncillo
authors.forename: Elena
authors.initials: E
authors.lastname: Usandizaga
authors.forename: Jacobo
authors.initials: J
authors.lastname: Silva
authors.forename: Cruz
authors.initials: C
authors.lastname: Rodríguez-Bobada
authors.forename: José Luis
authors.initials: JL
authors.lastname: Rojo
authors.forename: Nicasio
authors.initials: N
authors.lastname: Pérez-Castellano
authors.forename: Sergey
authors.initials: S
authors.lastname: Mironov
authors.forename: Lluis
authors.initials: L
authors.lastname: Mont
authors.forename: Teresa
authors.initials: T
authors.lastname: Pérez de Prada
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
authors.forename: Julián
authors.initials: J
authors.lastname: Pérez-Villacastín
mesh_terms: 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*
chemical_list: D000638:Amiodarone