Role of balloon occlusion for mononuclear bone marrow cell deposition after intracoronary injection in pigs with reperfused myocardial infarction
Role of balloon occlusion for mononuclear bone marrow cell deposition after intracoronary injection in pigs with reperfused myocardial infarction
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DOI：
10.1093/eurheartj/ehn218
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发表时间：
2008-08-01
影响因子：
39.3
通讯作者：
Muelller-Ehmsen, Jochen
中科院分区：
文献类型：
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作者：
Tossios, Paschalis;Krausgrill, Benjamin;Muelller-Ehmsen, Jochen
目的在急性心肌梗死（MI）的细胞治疗临床研究中，细胞通常通过球囊冠状动脉内输注（IC/B）应用。要测试的效用，球囊闭塞，单核骨髓细胞（MNC）保留后，冠状动脉内输注无球囊（IC/无B）与IC/B和intramocyte（IM）injection.Methods和结果4小时后，LAD结扎在雄性猪，再灌注被允许（证实冠状动脉造影）。5天后，通过IC/无B（n = 4）、IC/B（n = 4）或IM（n = 4）注射1 x 10（8）个自体（111）铟标记MNC。1 h时，IC/无B注射后，在心脏中检测到的注射MNC分数为4.1 +/- 1.1%，IC/B注射后为6.1 +/- 2.5%（P = 0.19），IM注射后为20.7 +/- 2.3%（P < 0.001 vs. IC/无B和IC/B）。在24 h时，其为3.0 +/- 0.6%（IC/无B）、3.3 +/- 0.5%（IC/B，P = 0.43）和15.0 +/- 3.1%（IM，P < 0.001 vs. IC/无B和IC/B）。在四次连续IC/B注射中的每一次期间的动态荧光图显示在球囊膨胀期间（无流动期，阶段1）快速的19.6 +/- 8.0%细胞损失和在球囊收缩之后（再流动期，阶段2）快速的36.6 +/- 17.8%细胞损失。在四次连续IC/noB注射中的每一次之后，峰值细胞存款较低，随后是一个阶段的快速细胞损失（6分钟后30.9 +/-11.0%）。IM注射后，仅观察到缓慢的线性细胞损失（9.7%/h）。在组织学上，PKH-67标记的细胞只有很少有通过内皮屏障后24小时IC注射，而他们被专门发现在IM injection.Conclusion后IC注射与球囊闭塞后，一个类似的细胞持久性的观察表明，目前在临床研究中应用的球囊程序是没有必要的细胞存款。如果细胞的长期存留对心脏细胞疗法的临床益处起作用，则IM注射可能上级IC应用。
Aims In clinical studies on cell therapy for acute myocardial infarction (MI), cells are usually applied by intracoronary infusion with balloon (IC/B). To test the utility of balloon occlusion, mononuclear bone marrow cell (MNC) retention after intracoronary infusion without balloon (IC/noB) was compared with IC/B and intramyocardial (IM) injection.Methods and results Four hours after LAD ligation in male pigs, reperfusion was allowed (confirmed by coronary angiography). Five days later, 1 x 10(8) autologous (111)Indium-labelled MNC were injected IC/noB (n = 4), IC/B (n = 4), or IM (n = 4). At 1 h the fraction of injected MNC that was detected in the heart was 4.1 +/- 1.1% after IC/noB injection, 6.1 +/- 2.5% after IC/B injection (P = 0.19), and 20.7 +/- 2.3% after IM injection (P < 0.001 vs. IC/noB and IC/B). At 24 h it was 3.0 +/- 0.6% (IC/noB), 3.3 +/- 0.5% (IC/B, P = 0.43), and 15.0 +/- 3.1% (IM, P < 0.001 vs. IC/noB and IC/B). Dynamic scintigrammes during each of four consecutive IC/B injections showed a rapid 19.6 +/- 8.0% cell loss during balloon inflation (no-flow period, phase 1) and a rapid 36.6 +/- 17.8% cell loss after balloon deflation (re-flow period, phase 2). After each of four consecutive IC/noB injections the peak cell deposit was lower, followed by one phase of rapid cell loss (30.9 +/- 11.0% after 6 min). After IM injection only a slow linear cell loss was observed (9.7% per h). In histology, PKH-67 labelled cells only rarely had passed the endothelial barrier after 24 h after IC injection, while they were exclusively found in the interstitium after IM injection.Conclusion The observation of a similar cell persistence after IC injections with and without balloon occlusion suggests that the balloon procedures currently applied in clinical studies are not necessary for cell deposit. If longer term persistence of cells plays a role for the clinical benefit of cardiac cell therapy, IM injection may be superior to IC applications.