Clinical and Experimental Interventional Cardiology, University of Saarland, Homburg/Saar, Germany.
InnoRa GmbH, Berlin, Germany.
Int J Cardiol. 2021 May 15;331:46-56. doi: 10.1016/j.ijcard.2020.12.071. Epub 2021 Jan 5.
Local administration of growth-inhibiting substances such as paclitaxel or sirolimus could reduce the risk of restenosis. In the drug coated balloon (DCB) technology the coating and the applied dose seem to play a major role. The aim of the present preclinical studies was to investigate the efficacy and safety of a specific DCB with paclitaxel as active ingredient and magnesium stearate as excipient.
Evaluation of the coating, drug release and transfer was done ex vivo and in vivo on peripheral arteries. A porcine coronary stent model was chosen to provoke intimal thickening. Conventional uncoated balloons were compared with paclitaxel urea and paclitaxel magnesium stearate coated balloons. QCA and histomorphometry was performed on treated vessels. Three areas of the heart were histologically examined for pathological changes.
QCA and histomorphometry revealed no differences in baseline data between treatment groups. All DCB groups showed a significant reduction of angiographic and histologic parameters describing neointimal formation 4 weeks after treatment (e.g. mean angiographic late lumen loss all coated 0.31 ± 0.18 mm versus 0.91 ± 0.37 mm in the uncoated balloon group). There were no device-related animal deaths or clinical abnormalities. In spite of very slight-to-slight microscopic findings limited to small arterial vessels in downstream tissue there was no change in left ventricular ejection fraction or angiographic presentation of small side branches of treated arteries.
Paclitaxel DCB using stearate as excipient show a high efficacy in reducing neointima formation after experimental coronary intervention. No evidence of myocardial damage resulting from distal embolization was found.
局部给予生长抑制物质，如紫杉醇或西罗莫司，可降低再狭窄的风险。在药物涂层球囊（DCB）技术中，涂层和应用剂量似乎起着主要作用。本临床前研究的目的是研究一种含有紫杉醇作为活性成分和硬脂酸镁作为赋形剂的特定 DCB 的疗效和安全性。
在体外和体内对周围动脉进行涂层、药物释放和转移的评估。选择猪冠状动脉支架模型来引发内膜增厚。将常规未涂层球囊与紫杉醇脲和紫杉醇硬脂酸镁涂层球囊进行比较。对处理过的血管进行 QCA 和组织形态计量学检查。对心脏的三个区域进行组织学检查以观察病理变化。
QCA 和组织形态计量学显示治疗组之间的基线数据无差异。所有 DCB 组在治疗后 4 周时均显示出血管造影和组织学参数描述的新生内膜形成显著减少（例如，所有涂层的平均血管造影晚期管腔丢失为 0.31±0.18mm，而未涂层球囊组为 0.91±0.37mm）。没有与器械相关的动物死亡或临床异常。尽管下游组织中小动脉的显微镜检查结果仅为轻微至轻度，但左心室射血分数或治疗动脉小侧支的血管造影表现没有变化。
使用硬脂酸镁作为赋形剂的紫杉醇 DCB 在减少实验性冠状动脉介入后的新生内膜形成方面具有很高的疗效。未发现由远端栓塞引起的心肌损伤的证据。
