摘要：
目的 通过两种国产成形环动物实验的病理学分析,探索建立规范的成形环临床前体内实验的病理评价方法.方法 通过外科手术将两种国产瓣膜成形环及其对照产品分别植入17只(实验组)和5只(对照组)成年小尾寒羊的二尖瓣位或三尖瓣位,术后20周处死羊,通过大体观察、组织病理学和扫描电镜等方法观察手术相关损伤、成形环的完整性、炎性反应、内皮化和纤维鞘形成、纤维组织过度生长、血栓形成等情况,对于心、肝、脾、肺、肾、脑等脏器梗死和感染等情况进行评估,对实验终点前死亡的羊进行死因分析,判断死亡与成形环的关系,从而评价其安全性.结果 所有羊的成形环植入位置准确,成形环完整,未见折断或裂开,未见瓣叶及冠脉等手术损伤.除4只羊(实验组3只、对照组1只)分别于术后2、11、12和13周死亡外,术后满20周的羊,成形环表面纤维鞘均较完整,未见血栓及纤维组织过度生长.成形环周围见少量淋巴细胞及多核巨细胞浸润,实验组1例炎性反应较重,可见中性粒细胞.实验组成形环表面内皮化率[(92.0±8.1)％]与对照组内皮化率[(97.0±2.4)％]的差异无统计学意义(P=0.081).6例可见小灶心肌坏死,1例小灶肾梗死,1例自发性肉芽肿性肝炎.未达实验终点的4只羊均死于肺部感染,其中3只羊(实验组2只,对照组1只)纤维鞘不完整,内皮化率5％ ～60％,1只(实验组)血栓形成,1只小灶心肌坏死.结论 针对瓣膜成形环的规范的病理评价应在不同的形态学水平对产品完整性、局部组织相容性和远端器官并发症等方面进行系统的观察,并注意鉴别手术操作、术后感染及植入材料不良反应与术后并发症或动物死亡的关系,客观、准确地评价植入材料的安全性.%Objective The pathological evaluation is an important aspect in the preclinical research of cardiovascular devices.The aim of the study was to set up a pathological evaluation strategy for preclinical safety study of annuloplasty rings.Methods Total 22 annuloplasty rings were implanted separately in 22 adult male sheep,including 17 sheep in the test group of two kinds of new rings and 5 sheep in the control group.The implant position was the mitral valve in 17 sheep and the tricuspid valve in 5 sheep.When the animals were sacrificed 20 weeks after surgery,pathological examination was performed to evaluate the integrity of the annuloplasty rings,inflammatory reaction,endothelization,fibrous sheath,pannus,thrombosis at the gross,histological and ultrastructural levels.We also evaluated the injury of the heart and remote organs.Results All rings appeared well implanted at the mitral or tricuspid valves without any surgical injury on valves and coronary arteries.The annulopasty rings were well in the structural integrity and encapsulated by a thin fibrous sheath without thrombus and pannus.A few lymphocytes,macrophages and multinuclear giant cells were observed around the rings in all sheep while neutrophil infiltration was found only in 1 sheep of the test group.Scanning electron microscopy showed almost complete endothelization on the surface of rings.There was no significant difference of endothelization rate between the two groups [(92.0 ± 8.1) ％ vs.(97.0 ±2.4) ％,P =0.081].Other changes included focal myocardial necrosis in 6 sheep,kidney infarction in 1 sheep and granulomatous inflamation of liver in 1 sheep.Unexpected death occurred in 4 sheep (3 in the test group and 1 in the control group) at the 2nd,11th,12th and 13th week after surgery respectively.Their causes of death were regarded as pulmonary infection while autopsy also found incomplete fibrous sheath and lower endothelization rate of 5％ to 60％ in 3 sheep and a micro thrombi in 1 sheep.Conclusion A good pathological evaluation about annuloplasty rings should focus on the structural integrity,biocompatibility and complication of the heart and other organs at several morphological levels.It is important for preclinical safety study to differentiate adverse effect of annuloplasty rings,surgical injury and infection as the cause of complications and death.
