Department of Radiology, University of Heidelberg Medical Center, INF 110, 69120 Heidelberg, Germany.
J Vasc Interv Radiol. 2009 Dec;20(12):1608-16. doi: 10.1016/j.jvir.2009.08.019.
In part 1 of the present study, the authors demonstrated that coronary paclitaxel uptake from drug eluting stents (DESs) was not dependent on exposure time and dose. In this second part, the effect of the different paclitaxel dose densities on long-term biologic behavior was evaluated.
In 40 minipigs, (with 4- and 12-week follow-up), identical stents with the same three paclitaxel dose densities as in part 1 were implanted in the right coronary artery. Minipigs implanted with Polyzene-F nanocoated stents served as the control group. Quantitative angiography measuring average luminal diameter (from three in-stent reference points), minimal luminal diameter (from the point of maximum in-stent stenosis), average late loss, maximum late loss, and binary stenosis rate was performed, as was microscopy to determine neointimal thickening, injury score, and inflammation.
All three DESs were associated with a high average late loss, binary stenosis rate, and neointimal thickening, without significant differences. Drug-free stents had significantly less late in-stent stenosis: there was an average late loss of 0.3 mm +/- 0.3 in drug-free stents versus 0.8 mm +/- 0.2 in intermediate-dose stents and 1.5 mm +/- 0.6 in high-dose stents (P = .04). DES-associated inflammation was high in all DESs and six times higher as in the drug-free stents (Kornowski scores of 0.2 +/- 0.1 in drug-free stents, 1.3 +/- 0.9 in low-dose stents, 1.7 +/- 0.8 in intermediate-dose stents, and 1.3 +/- 1.0 in high-dose stents; P = .04). It worsened with time in all DESs, as did late in-stent stenosis.
The extensive and long-term retention of paclitaxel even in a low-dose formulation, at least according to the present labeling of DESs, might be associated with negative long-term results with regard to inflammation and late in-stent stenosis.
在本研究的第一部分，作者证明了药物洗脱支架（DES）中紫杉醇的摄取量不依赖于暴露时间和剂量。在第二部分，评估了不同紫杉醇剂量密度对长期生物学行为的影响。
在 40 只小型猪中（4 周和 12 周的随访），在右冠状动脉中植入与第一部分相同的三种紫杉醇剂量密度的相同支架。植入 Polyzene-F 纳米涂层支架的小型猪作为对照组。进行定量血管造影术测量平均管腔直径（来自三个支架内参考点）、最小管腔直径（来自支架内最大狭窄点）、平均晚期损失、最大晚期损失和二元狭窄率，并进行显微镜检查以确定新生内膜增厚、损伤评分和炎症。
所有三种 DES 都与高平均晚期损失、二元狭窄率和新生内膜增厚有关，没有显著差异。无药物支架的晚期支架内狭窄明显减少：无药物支架的平均晚期损失为 0.3mm±0.3mm，而中等剂量支架为 0.8mm±0.2mm，高剂量支架为 1.5mm±0.6mm（P=0.04）。所有 DES 相关的炎症反应均较高，与无药物支架相比，炎症反应高 6 倍（无药物支架的 Kornowski 评分分别为 0.2±0.1、低剂量支架为 1.3±0.9、中剂量支架为 1.7±0.8，高剂量支架为 1.3±1.0；P=0.04）。所有 DES 均随时间恶化，晚期支架内狭窄也随之恶化。
根据目前 DES 的标签，即使是低剂量制剂，紫杉醇的广泛和长期保留也可能与炎症和晚期支架内狭窄的负面长期结果有关。
