Endocardial electrogram analysis after intramyocardial injection of mesenchymal stem cells in the chronic ischemic myocardium.
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.
Krause
Korff
K
Department of Cardiology and Heart Surgery, Asklepios Hospital St. Georg, Hamburg, Germany. korff.krause@web.de
Schneider
Carsten
C
Lange
Claudia
C
Kokturk
Bulent
B
Boczor
Sigrid
S
Geidel
Stephan
S
Salhi
Ahmed
A
Alaser
Jusuf
J
Zander
Axel R
AR
Kuck
Karl-Heinz
KH
Jaquet
Kai
K
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