Mesenchymal stem cell injection ameliorates the inducibility of ventricular arrhythmias after myocardial infarction in rats.
Mesenchymal stem cell injection ameliorates the inducibility of ventricular arrhythmias after myocardial infarction in rats.
复制标题
DOI：
10.1016/j.ijcard.2010.07.025
复制
发表时间：
2011-11
影响因子：
3.5
通讯作者：
Deguo Wang;Fengxiang Zhang;Wenzhi Shen;Minglong Chen;Bing Yang;Yuzhen Zhang;K. Cao
中科院分区：
文献类型：
--
作者：
Deguo Wang;Fengxiang Zhang;Wenzhi Shen;Minglong Chen;Bing Yang;Yuzhen Zhang;K. Cao
间充质干细胞移植是改善心肌梗死（MI）后心功能的一种有前景的新疗法。MSC植入的电生理后果还没有系统地studied. METHODS我们调查了间充质干细胞（MSCs）治疗在实验性梗死模型的电生理和促血管生成的影响。结扎左前降支（LAD）建立心肌梗死模型，随机分为心肌内注射PBS（MI-PBS）组和5× 105 EGFP标记的MSCs（MI-MSCs）组。细胞移植后2周，应用程序电刺激（PES）检测MSC诱导的室性心动过速（VT），心室颤动阈值（VFT）和心室有效不应期（VERP）。与PBS处理的心脏相比，MSC植入导致左室心外膜梗死边缘区（IBZ）的动作电位时程（APD）明显延长，激动时间（AT）明显缩短。组织学检查显示，MI-MSC组梗死区纤维化面积和胶原沉积明显低于MI-PBS组。Connexin 43的异常改变，包括减少和偏侧化，均被MSC治疗显著减弱。CONCLUSION本研究提供了强有力的证据，证明MSC植入可改善间质纤维化和间隙连接的重塑，减弱局灶性的不均一性，降低室性心动过速的易感性。结果表明，MSC移植可能成为一种新的预防策略，对VA除了改善缺血性心脏病的心脏功能。
BACKGROUNDMesenchymal stem cell transplantation is a promising new therapy to improve cardiac function after myocardial infarction (MI). The electrophysiological consequences of MSC implantation has not been systematically studied.METHODSWe investigated the electrophysiological and arrhythmogenic effects of mesenchymal stem cells (MSCs) therapy in experimental infarction model. Rats were subjected to MI operation by LAD ligation and randomly allocated to receive intramyocardially injection PBS (MI-PBS) or 5×105EGFP labeled MSCs (MI-MSCs). Electrophysiological study, histological examination, and western blotting were performed 2weeks after cell transplantation.RESULTSProgrammed electrical stimulation (PES) showed a significant reduced inducible ventricular tachycardias (VTs), raised ventricular fibrillation threshold (VFT) and prolonged ventricular effective refractory period (VERP) in MSC-treated rats compared to PBS-treated animals. MSC implantation led to markedly longer action potential duration (APD) and shorter activation time (AT) in infarcted border zone (IBZ) of left ventricular epicardium compared with PBS-treated hearts. Histological study revealed that fibrotic area and collagen deposition in infarcted region were significantly lower in MI-MSC group than in MI-PBS group. Abnormal alterations of Connexin 43 including reduction and lateralization were significantly attenuated by MSC treatment.CONCLUSIONSThis study provide strong evidence that MSC implantation ameliorates interstitial fibrosis and the remodeling of gap junction, attenuates focal heterogeneity of reporlarization and conduction and reduces vulnerability to VTs. The results suggest that MSC transplantation might emerge as a new preventive strategy against VAs besides improving cardiac performance in ischemic heart disease.