Krause Korff, Schneider Carsten, Lange Claudia, Kokturk Bulent, Boczor Sigrid, Geidel Stephan, Salhi Ahmed, Alaser Jusuf, Zander Axel R, Kuck Karl-Heinz, Jaquet Kai
Department of Cardiology and Heart Surgery, Asklepios Hospital St. Georg, Hamburg, Germany.
Pacing Clin Electrophysiol. 2009 Oct;32(10):1319-28. doi: 10.1111/j.1540-8159.2009.02483.x. Epub 2009 Aug 19.
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.
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.
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.
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.
细胞注射疗法已被用于治疗冠心病患者。然而,心肌内注射骨髓源性细胞可能会产生致心律失常性。
在放置回旋动脉-阿梅洛德缩窄器两周后,21头猪使用机电标测(EMM)引导的经皮经心内膜注射导管接受间充质干细胞(MSC,n = 9)、单核(骨髓)源性干细胞(MNC,n = 6)和安慰剂(n = 6)。在第6周时,重复进行EMM,并对注射区域进行详细分析,以评估局部双极电图的碎裂、持续时间和振幅。通过定量组织学分析评估心肌纤维化。
在第6周时,注射MSC或MNC并未增加局部电图碎裂(MSC组:1.4±0.3对1.3±0.2;MNC组:1.4±0.2对1.3±0.2;P =无显著性差异),未延长电图持续时间(MSC组:27.1±7.8毫秒对23.7±2.0毫秒;MNC组:27.8±3.5毫秒对26.8±5.6毫秒;P =无显著性差异),也未降低双极电压(MSC组2.7±0.9毫伏对2.8±1.0毫伏;MNC组2.0±1.0毫伏对1.7±0.4毫伏)。从第2周到第6周,仅MSC组的平均左心室射血分数增加(37.9±4.2%对45.9±2.2%;P = 0.039)。对缺血区域的组织学分析显示,MNC组心肌纤维化率为17.6±5%,MSC组为13.6±3.4%,对照组为28.7±8.7%(P = 0.038和P = 0.013)。注射后任何动物均未死亡。
心肌内注射MSC或MNC不会增加注射的缺血心肌内心电图的碎裂和持续时间,但可减轻缺血损伤,因此可能不会为折返性心动过速创造电生理基质。