Visualization and comparison of drug effects after local paclitaxel delivery with different catheter types
Visualization and comparison of drug effects after local paclitaxel delivery with different catheter types
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DOI：
10.1007/s003950050161
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发表时间：
1999-10
影响因子：
9.5
通讯作者：
C. Herdeg;M. Oberhoff;A. Baumbach;A. Blattner;A. Küttner;S. Schröder;K. Haase;K. Karsch
中科院分区：
文献类型：
--
作者：
C. Herdeg;M. Oberhoff;A. Baumbach;A. Blattner;A. Küttner;S. Schröder;K. Haase;K. Karsch
背景：微管稳定剂紫杉醇在体外和体内均被证明对血管平滑肌细胞具有明显的抗增殖作用。它诱导细胞修饰，通过改变细胞微管平衡向组装方向移动，导致增殖、迁移和信号转导减少。方法和结果：本研究选择了3种导管--多孔球囊、微孔球囊和双球囊导管，代表了从被动到主动的压力驱动给药的光谱。40只新西兰大白兔右颈动脉电刺激形成明确斑块后，32只动物行球囊扩张，8只动物作为介入前单纯电刺激对照组。24只动物(每组8只)随后进行紫杉醇局部给药(10μ摩尔/L)。8只动物作为对照组，仅行血管成形术。介入治疗后1周切除血管。用抗溴脱氧尿核苷、α-肌动蛋白、巨噬细胞、von Willebrand因子和α-微管蛋白的抗体进行免疫组织化学染色。用电子显微镜分析细胞骨架的变化。微管蛋白染色和电子显微镜显示不同导管的染色模式不同。对于多孔性和双气囊导管，可以识别特殊的导管损伤。结论：紫杉醇诱导的细胞骨架改变可以通过微管和电子显微镜的染色来检测药物的作用。这使得能够在没有标记物质的情况下直接在血管系统中评估转移、分布和药物效果。双气囊导管似乎最适合紫杉醇的局部治疗。
Background:The microtubule stabilizing compound paclitaxel has proved to have potent antiproliferative effects on smooth muscle cells both in vitro and in vivo. It induces cellular modifications that result in reduced proliferation, migration and signal transduction by shifting the cellular microtubule equilibrium towards assembly. We therefore reasoned that a visualization of the altered cytoskeleton could enable an evaluation of the drug effects following local drug delivery.Methods and results:3 catheters – the porous balloon, the microporous balloon and the double balloon catheter – were chosen for this study representing the spectrum from passive to active, pressure-driven delivery. After the induction of a defined plaque in the right carotid arteries of 40 New Zealand rabbits by electrical stimulation, 32 animals underwent balloon dilatation and 8 animals served as pre-interventional control group with electrostimulation only. In 24 animals (n = 8 in each group) subsequent local paclitaxel delivery (10μmol/L) was performed. 8 animals served as control with angioplasty only. Vessels were excised 1 week following intervention. Immunohistochemistry with antibodies against bromodeoxyuridine, alpha-actin, macrophages, von Willebrand factor and α-tubulin was performed. Cytoskeletal changes were analyzed by electron microscopy. Tubulin staining and electron microscopy revealed changes with distinct staining patterns for the different catheters. Specific catheter-induced injuries could be identified for the porous and double balloon catheter. Intimal proliferation, percentage of macrophages and extent of injury favor the double balloon catheter for local paclitaxel delivery.Conclusions:The alterations of the cytoskeleton induced by paclitaxel allowed for the detection of drug action by staining of tubulin and electron microscopy. This enables an evaluation of transfer, distribution and drug effects directly in the vasculature without marker substances. The double balloon catheter appears to be best suited for local paclitaxel therapy.