背景和目的 肺动脉栓塞（pulmonary embolism ，PE）是仅次于冠心病、高血压病的严重危害人类 健康的急性心血管系统的病变。它发病急促，临床表现复杂多变且缺乏特异性，难于被 早期发现、早期诊断，死亡率较高。约 90％-95％肺栓塞病人的栓子源自深静脉系统血 栓，规律的肝素加华法林抗凝治疗虽然有显著临床疗效，但仍有高达 20%的患者发生肺 栓塞。对于这些在抗凝治疗时仍有发生肺栓塞危险的患者，游离或大块中心静脉血栓形 成者，盆腔静脉、下肢深静脉等大静脉血栓已形成但需手术或肢体活动的患者，单纯抗 凝治疗是不够的，下腔静脉滤器(inferior vena cava filter，IVCF)无疑是一个较好的选择， 它可在一定程度上减少或者避免肺动脉栓塞的发生，降低死亡率。下腔静脉滤器大致可 分为永久型滤器、可回收型滤器两种类型。永久型滤器虽可减少致死性肺栓塞的发生率， 但置入滤器术后的患者仍需长期服用抗凝药物，尽管如此，滤器远期完全闭塞的发生率 仍较高，深静脉血栓形成的复发率显著大于非手术组；随着滤器置入时间的延长，滤器 移位、血管穿孔等并发症发生率不断增加，患者最终的病死率和死亡率没有下降。因此， 既可有效过滤血栓、又能在适当时间内回收的可回收型滤器逐渐成为发展的方向。可回 收型静脉滤器不仅具有永久型滤器的优点，还可在放置滤器的动因消除后适时取出，目 前在临床上得到广泛应用。但在实际临床应用中，可回收型滤器也不是完美的。它在血 管内留置时间不长，一般在 12-14 天左右，如果留置时间过长，滤器容易与由于炎症刺 激等因素引起的过度增生的血管内膜组织发生粘连，致使滤器回收失败；当强行回收滤 器时可致血管内膜或血管壁撕裂，引起严重并发症。可回收型下腔静脉滤器的发展进入 瓶颈阶段。 基于心脏介入治疗的启发，我们认为带有药物涂层的可回收下腔静脉滤器会像心脏 介入治疗应用的药物洗脱支架一样减少血管局部的炎症反应、阻止血管内膜的过度增 生，使得滤器置入的时间延长并易于取出。本研究的目的是探讨药物涂层下腔静脉滤器 的临床可行性。本研究的第一阶段即通过在动物下腔静脉内植入金属裸支架及涂有抑制 血管内皮增生药物的药物涂层支架，观察支架植入后血管内皮增生情况。1.实验分组 选择 20 只健康日本大耳兔作为实验动物。随机分成两组，实验组为下腔静脉内植 入药物涂层支架组，对照组为下腔静脉内植入金属裸支架组。 2.方法 首先将实验动物按 60ng/Kg/天的剂量喂入华法林钠，待华法林血浆浓度稳定后，在 美国 GE 公司的 DSA 平板机下分别给实验动物组及对照组植入支架。支架植入术后继续 喂动物华法林，并分别于支架植入术后 7 天、15 天、30 天、60 天空气栓塞处死实验动 物取出带支架的下腔静脉，置于 10%多聚甲醛溶液中固定 24 h 后，将血管纵切，肉眼 观察支架植入处血管内皮增生情况；取下支架，将该段下腔静脉固定，包埋，切片，染 色，显微镜下观察并测量新生内皮的厚度。资料数据均以均数±标准差表示，采用 SPSS13.0 统计软件进行单因素方差分析，两组间均数比较采用 t 检验。以 α=0.05 为检 验水准，P<0.05 为差异具有显著性。 结果 1. 将植入支架术后 7d、15d 、30d、60d 的实验动物分别空气栓塞处死，取出带支架的 下腔静脉（支架前后各余 2mm-3mm），置于 10%多聚甲醛溶液中固定 24 h 后，纵切下 腔静脉，可见支架植入术后 7 d，裸支架组与药物支架组支架植入处下腔静脉内膜增生 情况无明显区别，在支架节段内未见新生内皮增长，支架均非常容易从下腔静脉上剥离； 支架植入术后 15 d，裸支架组支架内壁有不完全的内皮覆盖；而药物支架组内壁未见明 显的新生内皮，支架仍旧非常容易从下腔静脉上剥离；植入术后 30 d、60 d，纵切标本 发现裸支架组和药物支架组支架内壁均被半透明的新生内皮完全覆盖。 2. 将剥离支架的下腔静脉固定、包埋、染色、切片，显微镜下观察并测量内皮增生的平 均厚度，30 天内药物涂层支架较金属裸支架的新生内皮的厚度差异有统计学意义 （P<0.05）。 3．血管中膜及外膜承受来自支架结构的压力程度越重，新生内皮的增生程度就越明显。 4.支架植入处血管局部的炎症反应实验动物组较对照组轻。 结论 1.在实验动物身上，药物涂层支架在 30 天内防止内皮过度增殖方面优于裸支架，而在 60 天时两者内皮增殖情况没有明显区别。 2.内皮增生的程度不仅与支架结构分布有关，还与支架对血管中膜、外膜的压迫程度有 材料和方法关。 3.药物涂层支架血管局部的炎症反应较裸支架轻。 关键词 下腔静脉滤器，深静脉血栓形成，肺栓塞ABSTRACT Background: Pulmonary embolism (PE) is an acute cardiovascular system disease threatening human health and costing lives secondary only to coronary artery disease and hypertension. Its insidious onset and rapid progression with a variety of nonspecific clinical manifestations complicate early detection and accurate diagnosis, resulting in relatively high mortality. It has been reported that in PE patients approximately 90-95% of emboli originated from deep vein thrombosis (DVT). Despite routine anticoagulation using a combination of heparin plus warfarin PE still develops in up to 20% of patients. It is well recognized that in high risk PE patients simple anticoagulation is inadequate. Such patients include at least those with pelvic vein thrombosis, lower extremity deep vein thrombosis, and recurrent DVT/PE despite adequate anticoagulation. In these patients inferior vena cava filter (IVCF) could be a better choice of treatment to certain degree, because this device minimizes the risk or prevent PE formation so that mortality may be decreased. In general there are two different types of IVCF: permanent and recyclable/removable. Although fatal PE incidence is decreased in patients with permanent IVCF, these patients still require long-term anticoagulation. Complete occlusion of permanent IVCF with prolonged follow-up remains an important concern. Recurrent DVT is significantly higher than those without IVCF. Other complications such as device migration and vascular perforation may increase with time. As a result the case-specific and total mortalities remain unchanged in patients with permanent IVCF. For all those reasons the recyclable/removable IVCF which effectively filters out emboli but is removable in appropriate time attracts major research and clinical interests. Recyclable IVCF may be removed from patients as dictated by clinical conditions such as improved symptoms or elimination of reversible causes for DVT. Such device retains the advantage of permanent IVCF. Nevertheless in clinical practice recyclable/removable IVCF is far from being perfect. This type of device may stay in body for a limited time of approximate 12-14 days. Prolonged implantation may cause adhesion to vascular endothelial membrane because of local inflammatory stimulation by the device with contacted tissue, resulting failure of device removal. Fatal complication can occur during forceful device explantation which causes vascular wall tear andlaceration. Currently the development of recyclable/removable IVCF reaches the bottle-neck stage. Hypothesis and Objectives: As interventional cardiologists we hypothesize that recyclable/removable IVCF coated with drugs that inhibit local inflammation and tissue growth just like drug-elute stent may inhibit vascular endothelial proliferation, therefore prolong the time of implantation and facilitate device removal. The overall objective of this study is to explore the clinical feasibility of drug-coated recyclable/removable IVCF. The first phase of this study is to compare the differences in local and systemic responses including retrievability in experimental animals implanted with drug elute stents (DES) and bare metal stents (BMS). Materials And Methods 1. Experimental Groups Age and weight matched 20 Japanese big-ear rabbits were randomly divided into two groups to receive either drug elute stents (experimental) or bare metal stents (control). 2. Methods Animals were fed with warfarin at a dose of 60ng/kg/day for 7 days until plasma drug concentration was at steady-state. Under general anesthesia DES or BMS was implanted in IVC in catheterization laboratory using DSA flat plate (GE, USA). Warfarin was continued after stent implantation. Animals were euthanized by air embolization at experimental day 7, 15, 30, and 60. Stented IVC segments with 2-3 mm vessel tissue on each ends were removed and placed in 10% polyphosphate formaldehyde solution for 24 hour-fixation. Thereafter longitudinal sections were made for gross inspection of vascular endothelial proliferation. After removing the stents, the vascular tissues were further fixed, embolded, sliced and stained for quantitative measurements of the thickness of neo-endotheliolization under microscopy. Data were expressed by mean +/- standard deviation. Statistical analysis was performed using softwar