title: Endocardial electrogram analysis after intramyocardial injection of mesenchymal stem cells in the chronic ischemic myocardium.
abstract: BACKGROUND
  Cell injection therapies have been introduced for the treatment of patients with coronary heart disease. However, intramyocardial injection of bone marrow (BM)-derived cells may generate proarrhythmogenicity.
  
  
  METHODS
  Two weeks after the placement of a circumflex artery-ameroid constrictor, 21 pigs received mesenchymal stem cells (MSC, n = 9), mononuclear (BM)-derived stem cells (MNC, n = 6), and placebo (n = 6) using a electromechanical mapping (EMM)-guided percutaneous transendocardial injection catheter. At week 6, EMM was repeated and the injected areas were analyzed in detail to evaluate local bipolar electrogram fragmentation, duration, and amplitude. Myocardial fibrosis was evaluated by a quantitative histological analysis.
  
  
  RESULTS
  At week 6, the injection of MSC or MNC did not increase local electrogram fragmentation (MSC group: 1.4 +/- 0.3 vs. 1.3 +/- 0.2; MNC group: 1.4 +/- 0.2 vs. 1.3 +/- 0.2; P = NS), prolong electrogram duration (MSC group: 27.1 +/- 7.8 ms vs. 23.7 +/- 2.0 ms; MNC group: 27.8 +/- 3.5 ms vs. 26.8 +/- 5.6 ms; P = NS), or decrease bipolar voltages (MSC group 2.7 +/- 0.9 mV vs. 2.8 +/- 1.0 mV; MNC group 2.0 +/- 1.0 mV vs. 1.7 +/- 0.4 mV). From week 2 to week 6, mean left ventricular ejection fraction increased in the MSC group (37.9 +/- 4.2% vs. 45.9 +/- 2.2%; P = 0.039) only. Histological analysis of the ischemic regions revealed 17.6 +/- 5% myocardial fibrosis in the MNC group vs. 13.6 +/- 3.4% MSC vs. 28.7 +/- 8.7% in the control group (P = 0.038 and P = 0.013). No death occurred in any animal after the injection procedure.
  
  
  CONCLUSIONS
  Intramyocardial injection of MSC or MNC do not increase fragmentation and duration of endocardial electrograms in the injected ischemic myocardium but attenuate ischemic damage and therefore may not create an electrophysiological substrate for reentry tachycardias.
authors.affiliation: Department of Cardiology and Heart Surgery, Asklepios Hospital St. Georg, Hamburg, Germany. korff.krause@web.de
authors.forename: Korff
authors.initials: K
authors.lastname: Krause
authors.forename: Carsten
authors.initials: C
authors.lastname: Schneider
authors.forename: Claudia
authors.initials: C
authors.lastname: Lange
authors.forename: Bulent
authors.initials: B
authors.lastname: Kokturk
authors.forename: Sigrid
authors.initials: S
authors.lastname: Boczor
authors.forename: Stephan
authors.initials: S
authors.lastname: Geidel
authors.forename: Ahmed
authors.initials: A
authors.lastname: Salhi
authors.forename: Jusuf
authors.initials: J
authors.lastname: Alaser
authors.forename: Axel R
authors.initials: AR
authors.lastname: Zander
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Kuck
authors.forename: Kai
authors.initials: K
authors.lastname: Jaquet
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000175:diagnosis* / Q000209:etiology*; D002908:Chronic Disease; D004562:Electrocardiography / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D017202:Myocardial Ischemia / Q000175:diagnosis* / Q000601:surgery*; D013552:Swine; D016896:Treatment Outcome