目的:调查当地,下游,以及两种不同的紫杉醇涂层球囊的全身效应。
方法:猪健康外周动脉模型的临床前研究,随机分配设备的分布:测试紫杉醇涂层球囊(PCB)(Luminor®),a控制PCB(in.PACT®),和普通血管成形术球囊(Oceanus®),考虑单(1×)和重叠(3×)剂量与简单的盲组织学分析。
方法:20只动物在两个股动脉的外部和内部分支中接受了1倍或3倍剂量的球囊血管成形术,并随访了28天。进行了术后和随访血管造影。综合尸检和组织学检查用于评估局部,下游和系统性影响。
结果:在所有动物中都成功进行了血管成形术。在三个动脉(用Oceanus®治疗)中出现明显的方案偏差,没有临床相关性。从分析中排除那些样品。所有动物都在随访期间存活,没有重大临床问题。与IN相比,Luminor®的局部药物毒性迹象较少。PACT®,1倍剂量,包括内皮丢失(p=0.0828),内膜/中膜炎症(p=0.0004),透壁内侧平滑肌细胞(SMC)损失(p=0.0016),壁厚损失(p=0.0141),血管壁中存在纤维蛋白(p=0.0054),和外膜炎症(p=0.0080)。在3倍剂量下观察到类似的内皮损失模式(p=0.0011),内膜/中膜炎症(p<0.0001),周向SMC损耗(p=0.0004),用蛋白聚糖替代内侧SMC(p=0.0014),纤维蛋白(p=0.0034),和胶原含量(p=0.0205)。下游血管组织学变化温和,尽管在IN中更为普遍。PACT®3×组(p=0.006)。在所分析的任何样品中均未检测到毒性的全身性影响。
结论:Luminor®显示出更好的愈合模式(较低的炎症,和内皮和肌肉损失)比IN。PACT®气球。在单剂量和三剂量时效果明显。下游病变的患病率,尽管很低,三剂IN较高。PACT®与Luminor®的比较。
OBJECTIVE: To investigate the local, downstream, and systemic effects of two different paclitaxel-coated balloons.
METHODS: Preclinical study in healthy peripheral arteries of a swine model, with randomized allocation of the distribution of the devices: the test paclitaxel-coated balloon (PCB) (Luminor®), a control PCB (IN.PACT®), and a plain angioplasty balloon (Oceanus®), considering single (1×) and overlapping (3×) doses with simple blind histologic analysis.
METHODS: Twenty animals underwent balloon angioplasty at 1× or 3× doses in the external and internal branches of both femoral arteries and were followed-up for 28 days. Post-procedural and follow-up angiography were carried out. Comprehensive necropsy and histology were used to evaluate the local, downstream and systemic effects.
RESULTS: Angioplasty was successfully carried out in all animals. Significant protocol deviations appeared in three arteries (treated with Oceanus®) without clinical relevance. Those samples were excluded from the analysis. All the animals survived the follow-up period without major clinical issues. Local signs of drug toxicity were less marked with Luminor® than IN.PACT® at 1× dose, including endothelial loss (p=0.0828), intima/media inflammation (p=0.0004), transmural medial smooth muscle cell (SMC) loss (p=0.0016), wall thickness loss (p=0.0141), presence of fibrin in the vascular wall (p=0.0054), and adventitial inflammation (p=0.0080). A similar pattern was observed at the 3× dose for endothelial loss (p=0.0011), intima/media inflammation (p< 0.0001), circumferential SMC loss (p=0.0004), medial SMC replacement with proteoglycans (p=0.0014), fibrin (p=0.0034), and collagen content (p=0.0205). Downstream vascular histologic changes were mild although more prevalent in the IN.PACT® 3× group (p=0.006). No systemic effects of toxicity were detected in any of the samples analyzed.
CONCLUSIONS: Luminor® showed better healing pattern (lower inflammation, and endothelial and muscular loss) than IN.PACT® balloon. The effect was evident at single and triple doses. The prevalence of downstream lesions, albeit low, was higher with the triple dose of IN.PACT® compared with Luminor®.