■动脉瘤的病理生理学仍然知之甚少,部分来自小鼠模型与人体生理的差异,以及侵入性主动脉暴露应用用于创建动脉瘤模型的药物的要求。开发了可回收的药物输注支架移植物(RDIS),以隔离主动脉壁以暴露于药物。我们假设RDIS可以提供促进动脉瘤的酶,以创建猪胸动脉瘤模型,而无需大量手术暴露。
■可回收的镍钛诺支架移植框架设计有一个隔离的药物输送室,用聚四氟乙烯覆盖,并且连接到具有安装到外部腔室的药物输注导管的递送线。机构动物护理和使用委员会批准的约克郡猪(n=5)经皮进入股动脉,基线主动脉造影和在胸主动脉中放置支架,然后暴露于弹性蛋白酶混合物30分钟,胶原酶,和胰蛋白酶.吸入过量药物后,支架取回,和股动脉修复,动物被恢复,在1周和4周进行血管造影,然后进行外植体。组织学分析,原位酶谱,并进行多重细胞因子测定。
■RDIS通过血管造影分离了前主动脉的一部分,而在药物治疗期间,中心管腔保留了远端灌注(基线股骨平均动脉压,70±14mmHg;RDIS后,75±12;P=.55)。胸动脉瘤的血管内诱导不需要事先的机械损伤,动物也没有发现毒性的证据。1周内,在所有5只动物中观察到显著的动脉瘤生长(基线1.4±0.1cm~2.9±0.7cm;P=.002),并且仅在主动脉的治疗区域内.动脉瘤持续到4周。动脉瘤组织学显示弹性蛋白和胶原蛋白的损失,否则会保留在未经处理的主动脉中。在动脉瘤内,促炎细胞因子和增加的基质金属蛋白酶活性显著增加。
■RDIS实现了隔离的药物递送,同时保留了远端灌注,以实现无需大手术的胸动脉瘤血管内猪模型。该模型可能对手术训练有价值,设备测试,并更好地了解动脉瘤的发病机制。最重要的是,尽管RDIS被用来模拟主动脉病理,该工具提供了有趣的视野,可将重点治疗药物直接输送到动脉瘤,更广泛地说,集中局部给药血管和血管床。
UNASSIGNED: Aneurysm pathophysiology remains poorly understood, in part from the disparity of murine models with human physiology and the requirement for invasive aortic exposure to apply agents used to create aneurysm models. A retrievable drug infusion stent graft (RDIS) was developed to isolate the aortic wall intraluminally for drug exposure. We hypothesized that an RDIS could deliver aneurysm-promoting enzymes to create a porcine model of thoracic aneurysms without major surgical exposure.
UNASSIGNED: Retrievable nitinol stent graft frames were designed with an isolated drug delivery chamber, covered with polytetrafluoroethylene, and connected to a delivery wire with a drug infusion catheter installed to the outer chamber. Institutional Animal Care and Use Committee-approved Yorkshire pigs (n = 5) underwent percutaneous access of the femoral artery, baseline aortogram and stent placement in the thoracic aorta followed by 30-minute exposure to a cocktail of elastase, collagenase, and trypsin. After aspiration of excess drug, stent retrieval, and femoral artery repair, animals were recovered, with angiograms at 1 and 4 weeks followed by explant. Histological analysis, in situ zymography, and multiplex cytokine assays were performed.
UNASSIGNED: The RDIS isolated a segment of anterior aorta angiographically, while the center lumen preserved distal perfusion during drug treatment (baseline femoral mean arterial pressure, 70 ± 14 mm Hg; after RDIS, 75 ± 12; P = .55).
Endovascular induction of thoracic aneurysms did not require prior mechanical injury and animals revealed no evidence of toxicity. Within 1 week, significant aneurysmal growth was observed in all five animals (1.4 ± 0.1 cm baseline to 2.9 ± 0.7 cm; P = .002) and only within the treated region of the aorta. Aneurysms persisted out to 4 weeks. Aneurysm histology demonstrated loss of elastin and collagen that was otherwise preserved in untreated aorta. Proinflammatory cytokines and increased matrix metalloproteinase activity were increased significantly within the aneurysm.
UNASSIGNED: An RDIS achieves isolated drug delivery while preserving distal perfusion to achieve an
endovascular porcine model of thoracic aneurysms without major surgery. This model may have value for surgical training, device testing, and to better understand aneurysm pathogenesis. Most important, although the RDIS was used to simulate aortic pathology, this tool offers intriguing horizons for focused therapeutic drug delivery directly to aneurysms and, more broadly, focused locoregional drug delivery to vessels and vascular beds.