Massive mechanical loss of microspheres with direct intramyocardial injection in the beating heart: Implications for cellular cardiomyoplasty
Massive mechanical loss of microspheres with direct intramyocardial injection in the beating heart: Implications for cellular cardiomyoplasty
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DOI：
10.1016/j.jtcvs.2006.05.034
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发表时间：
2006-09-01
影响因子：
6
通讯作者：
Shum-Tim, Dominique
中科院分区：
文献类型：
--
作者：
Teng, Carolyn J.;Luo, Jun;Shum-Tim, Dominique
目的：直接心肌内注射是心肌细胞治疗中常用的供体细胞给药途径。研究表明，植入细胞的显著和快速损失被认为是生物学原因。我们假设，从收缩心肌的细胞的机械损失实际上可能是主要的罪魁祸首。方法：在小型和大型动物模型进行了心肌内注射荧光微球（10 μ m）。刘易斯大鼠（250 - 350 g）的心脏接受3 × 10（6）微球注射到左心室心肌中。将大鼠平均分配给两名经验丰富的操作员。小猪（7.5 - 7.8 kg）的非跳动（n = 2）和跳动（n = 5）心脏接受3 × 10（6）微球。在10分钟内切除心脏，用荧光流式细胞术定量保留在心肌中的微球。在心脏跳动的大鼠模型中，单次注射后微球的保留率在有或没有针穿刺部位的荷包缝合堵塞的情况下是相似的，并且略低于多部位注射后的保留率（6.19%+/-4.05% vs 5.44%+/-5.66% vs 8.83%+/-3.29%）。没有显著的操作员依赖性差异。在不停跳猪心中的滞留率高于大鼠（P <.05），但明显低于停跳猪心（11.1%对67.4%）。机械渗漏和冲洗可能是细胞植入后细胞损失的主要原因，并且旨在减少跳动心脏中的机械损失的努力可能比仅针对生物损失的努力产生更大的益处。
Objective: Direct intramyocardial injection is a common route of donor cell administration for myocardial cell therapy. Studies have demonstrated a significant and rapid loss of implanted cells, which is thought to be biologically caused. We hypothesized that mechanical loss of cells from the contracting myocardium might actually be the main culprit.Methods: Intramyocardial injections of fluorescent microspheres (10 mu m) were carried out in both small and large animal models. The hearts of Lewis rats (250- 350 g) received 3 x 10(6) microspheres injected into the left ventricular myocardium. Rats were divided evenly between two experienced operators. The nonbeating (n = 2) and beating (n = 5) hearts of piglets (7.5- 7.8 kg) received 3 x 10(6) microspheres. The hearts were excised within 10 minutes, and the microspheres retained in the myocardium were quantified with fluorescent flow cytometry.Results: In the beating- heart rat model, the microsphere retention rates after a single injection were similar with and without purse- string occlusion of needle puncture sites and slightly lower than after multiple site injections (6.19% +/- 4.05% vs 5.44% +/- 5.66% vs 8.83% +/- 3.29%). There were no significant operator-dependent differences. The retention rates in beating porcine hearts were higher than those in the rats (P < .05) but markedly lower than those in nonbeating porcine hearts (11.1% vs 67.4%).Conclusion: Mechanical leakage and washout may account for a major portion of cell loss after cell implantation, and efforts aimed at reducing mechanical loss in the beating heart may yield a greater benefit than those targeting biologic loss alone.