title: Transplanted fetal cardiomyocytes as cardiac pacemaker.
abstract: BACKGROUND
  While morphologic integration of transplanted fetal cardiomyocytes into the ventricular myocardium is a well-known fact, no studies have yet shown transplanted cells to coherently contribute to contraction and electrical excitation of the host myocardium. The aim of this study was to prove the hypothesis that by transplanting cardiomyocytes with a higher intrinsic rhythmic rate into the myocardium of the left ventricle, these cells could act as an ectopic pacemaker by functional coupling with host cardiomyocytes.
  
  
  RESULTS
  Dissociated fetal canine atrial cardiomyocytes including sinus nodal cells were delivered into the free wall of the left ventricle of adult canine X-linked muscular dystrophy dogs (n=2). These dogs fail to express Dystrophin in both cardiac and skeletal muscle. In the control group (n=2) fetal skin fibroblasts were used for grafting. A total of 3-4 weeks after transplantation the dogs underwent catheter ablation of the atrioventricular node (AV-node) and subsequent electrophysiological mapping studies. Transplanted cells were identified by Dystrophin immunoreactivity, indicating survival and morphological integration in the recipient heart. The expression of Connexin 43 between donor and recipient cells suggested formation of gap junctions between injected and host cardiomyocytes. After catheter ablation of the AV-node, a ventricular escape rhythm emerged driving the pace of the heart and originating from the labeled transplantation site. This effect could not be observed in the control group (n=2).
  
  
  CONCLUSIONS
  The results constitute the first observation of phenomena indicating electrical and mechanical coupling between allogeneic donor cardiomyocytes and recipient myocardium in-vivo. Further experiments are necessary to evaluate the technique as a potential therapy for atrioventricular block.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Arjang
authors.initials: A
authors.lastname: Ruhparwar
authors.forename: Juergen
authors.initials: J
authors.lastname: Tebbenjohanns
authors.forename: Michael
authors.initials: M
authors.lastname: Niehaus
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
authors.forename: Thiemo
authors.initials: T
authors.lastname: Irtel
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kofidis
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Pichlmaier
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
mesh_terms: D000818:Animals; D001283:Atrioventricular Node / Q000601:surgery; D017690:Cell Transplantation; D004285:Dogs; D016189:Dystrophin / Q000235:genetics / Q000276:immunology; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D016332:Fetal Tissue Transplantation; D006329:Heart Conduction System / Q000502:physiology; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology*; D016277:Ventricular Function, Left / Q000235:genetics / Q000502:physiology*
chemical_list: D016189:Dystrophin