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Analysis of pro-arrhythmic effects induced by different routes of administration of bone marrow stem cells

机译：骨髓干细胞不同给药途径引起的心律失常作用分析

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There has been repeated concern that intramyocardial (i.m.) delivery of cells could cause ventricular arrhythmias. The aim of the study was to evaluate the pro-arrhythmic effects of bone marrow stem cell (BMSC) injection and compare different routes of administration. An ischemia reperfusion injury was induced in New Zealand rabbits by temporal ligation of anterior descending coronary artery. Homologous BMSCs were isolated, cultured and re-suspended for injection. We compared different routes of BMSC injections, intramyocardial (i.m.) versus intravenous (i.v.) administration of cells. A control group was treated with i.m. injections of saline. The hourly number of supra- and ventricular premature contractions (VPCs), QT interval time and QTc time were recorded and calculated. At Day 7 after cell injections, VPCs were more frequent in the groups treated with i.m. BMSCs and i.m. saline compared with i.v. BMSCs (132 ±19; 54±14 and 34±9, respectively; P<0.01 within groups), whereas at Day 21 the number of VPCs was higher in the 2 groups treated with either i.m. or i.v. BMSCs compared with saline (96±23; 52±19 and 25±20, respectively; P<0.001 within groups). QTc time interval was prolonged during ischemia, and recovered in control and in the group treated with i.v. cells, whereas it remained longer in rabbits treated with i.m. BMSCs. These findings show that i.m. BMSC injections induced a high number of pre-arrhythmic events suggesting changes in cardiac electrophysiological properties. The i.v. administration of cells resulted in lower VPC beats and in a temporary QT prolongation. These results suggest that the combination of BMS cells and i.m. injections induced an electrical remodeling that contributed to the development of arrhythmias.
机译：人们一直担心心肌内（i.m.）递送细胞会引起室性心律失常。该研究的目的是评估骨髓干细胞（BMSC）注射的促心律失常作用，并比较不同的给药途径。通过暂时结扎冠状动脉前降支，在新西兰兔中引起缺血再灌注损伤。分离出同源BMSC，对其进行培养并重悬进行注射。我们比较了BMSC注射的不同途径，心肌内（i.m.）与静脉内（i.v.）施用细胞。对照组接受i.m.注射盐水。记录并计算每小时的上，室早收缩（VPC）数，QT间隔时间和QTc时间。细胞注射后第7天，接受i.m.治疗的组中的VPC频率更高。 BMSC和i.m.生理盐水与静脉注射相比BMSCs（分别为132±19; 54±14和34±9;组内P <0.01），而在第21天，接受i.m处理的2组中的VPC数量更高。或i.v. BMSCs与生理盐水相比（分别为96±23; 52±19和25±20;组内P <0.001）。 QTc时间间隔在缺血期间延长，并且在对照组和经静脉内治疗的组中恢复。细胞，而在经i.m.处理的兔子中则保持更长的时间骨髓间充质干细胞。这些发现表明BMSC注射引起大量的心律失常前事件，提示心脏电生理特性发生了变化。 i.v.细胞的施用导致较低的VPC搏动和暂时的QT延长。这些结果表明BMS细胞和i.m.注射引起电重构，导致心律不齐的发展。

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