碘油／无水乙醇肝节段性栓塞的犬实验研究

目的：研究碘油／无水乙醇肝节段性栓塞术后肝脏的病理变化过程,及此过程中肝、肾功能的改变,为临床推广应用提供依据。材料和方法：以健康杂种犬为实验对象（n=12),碘油／无水乙醇（Lp/E,比例4;1）作为栓塞剂,行肝节段性栓塞,术前、术后监测血常规、淀粉酶、肝肾功能,术后定期复查肝动脉造影、CT并分批处死实验犬进行肝肺组织学检查。结果：术后定期复查肝动脉造影示靶肝动脉均明确闭塞。病理检查发现肝栓塞区小动脉血栓形成,1周后血栓机化,术后4周栓塞肝组织完全坏死,坏死肝细胞完全崩解,代之以纤维组织增生。术后1天白细胞出现一过性升高,术后1周即恢复术前水平。肝功能呈一过性损害,术后1－3周恢复术前水平,主要表现为ALT、AST、γ－GT、ALP和TBA的升高。结论：Lp/E具有确实的栓塞效果,能达到“内科性肝段切除”的目的。     

Dextran微球末梢性肝动脉栓塞治疗肝癌的实验研究及临床初步应用

采用Dextran微球G—50,φ50～150μ作实验性肝肾动脉栓塞及临床肝动脉栓塞治疗肝癌,并以1×1×1mm明胶海绵颗粒作近侧性肝动脉栓塞作为对照。研究结果表明:Dextran微球能产生更为均一、更为末梢的微动脉栓塞。动物实验及临床应用均表明,它能栓塞到直径约100μ的微动脉水平。实验动物肝动脉栓塞后8周,微球仍不为组织所吸收;人体肝动脉栓塞后16周微球依然存在。能有效地减少或阻止肝肿瘤患者肝动脉栓塞后肝内、外侧支循环的建立,栓塞对癌瘤主灶及子灶均有显著作用。因此,Dextran微球是一很有希望的长效栓塞剂。     

去甲斑蝥素微球对兔肝动脉栓塞作用的研究

目的观察去甲斑蝥素鄄海藻酸/聚酸酐微球(NAPMS)对兔肝动脉的栓塞作用。方法新西兰兔18只,在DSA下,行肝动脉造影后,以8mg/kg的剂量经肝动脉注入NAPMS,注入后10min、1,7、14、21和30d各取3只再次造影,观察肝动脉栓塞情况,并处死,取心、肝、肾、脾、肺、胰、胃等组织,观察病理变化,同时作肝、肾功能、血常规检查。结果兔肝动脉栓塞前,肝脏血管造影清晰,栓塞后10min造影,远端微血管消逝,肝动脉增粗、迂曲。介入栓塞后第1、7、14、21和30天造影远端血管均未显影。肝脏病理结果显示微球栓塞于肝窦前小动脉。栓塞后出现一过性肝功能损害,AST,ALT均在栓塞后1d达最高值,以后逐渐下降,7d左右恢复正常水平(P>0.05)。栓塞后白细胞出现一过性升高,第3天达最高值,第7天接近正常水平(P>0.05)。结论去甲斑蝥素微球具有良好的肝动脉末梢栓塞作用,栓塞时间在1个月以上,是较理想的介入栓塞剂。     

羟基喜树碱明胶微球肝动脉化疗栓塞治疗肝肿瘤的实验研究

目的：对羟基喜树碱明胶微球（ＯＰＴ－ｍｓ）进行栓塞特性的实验研究。方法：以草犬为实验对象，比较了肝动脉注射常规型ＯＰＴ，空白明胶微球和ＯＰＴ－ｍｓ对大鼠肝癌的作用，并以肝动脉注射生理盐水作对照。结果：发现微球栓塞后血管造影可见末梢动脉有不同程度的减少，３０ｄ复查未见侧支循环形成。ＡＫＰ，ＧＰＴ在肝动脉灌注后３ｄ可达到最大值，７ｄ后明显下降，１４ｄ恢复正常，肝功能指标与微球的剂量呈正相关。病理检查有局限性或小灶性坏死，其程度与范围与剂量的大小有关，其它主要脏器无明显改变。结论：ＯＰＴ－ｍｓ对于肝肿瘤治疗是理想的。     

介入法犬股骨头坏死模型制作

目的 应用介入方法建立犬股骨头坏死模型.方法 9只成年杂种犬全麻后,分别通过股动脉Seldinger法穿刺插管,超选一侧股骨头供血动脉行平阳霉素灌注及明胶海绵栓塞处理,建立股骨头缺血坏死模型,对侧股骨头作对照.模型犬随机分为3组,每组3只,分别于栓塞术后2、4、6周处死.所有犬均于栓塞术前及术后每周行双侧髋关节MRI扫描,栓塞术前、术后即刻、处死前行双侧股骨头供血动脉DSA造影检查,最后一次造影结束处死动物,取双侧股骨头标本送病理学观察.结果 9只犬均造模成功,术后所有栓塞动脉造影复查均未见再通.造模侧股骨头在术后2周出现早期病理学改变.术后4周MRI显示股骨头坏死异常信号,病理切片出现不同程度骨细胞及骨小梁坏死,术后6周病理切片可见坏死后增生及修复反应.结论 本法能成功制作出犬股骨头坏死模型,具有创伤小、造模方法简单、成模时间短、动物死亡率低等优点,是一种比较理想的造模方式.     

肝动脉栓塞与经肝静脉逆行栓塞联合应用的实验研究

目的：为了使肿瘤及载瘤肝段完全坏死，获得介入性肝段（叶）切除的效果，作者进行了肝动脉栓塞与经肝静脉逆行栓塞（ＴＨＡＥ－ＲＨＶＥ）联合应用的动物实验。材料和方法：８只健康犬进行了ＴＨＡＥ－ＲＨＶＥ，肝动脉栓塞时用带囊导管阻断区域肝静脉后，向相应区域肝动脉注入碘化油，再注入明胶海绵碎片；逆行栓塞肝静脉时，在球囊阻断肝静脉下注入无水酒精－泛影葡胺（１１）混合剂。对照组（单纯肝静脉逆行注入酒精）４只。术后复查肝功能、ＣＴ，定期处死实验动物，行肝脏及肺病理学检查。结果：ＴＨＡＥ－ＲＨＶＥ及对照组技术均成功，实验组与对照组肝功能指标均呈一过性增高。ＣＴ复查显示实验组碘油充填栓塞区肝段及所属门脉分支。实验组术后１周病理检查，栓塞区肝段呈完全性、凝固性坏死，肝静脉、门静脉分支壁厚，其内充满机化血栓，２周时坏死周围有肉芽组织及炎症细胞浸润，４～８周栓塞肝叶明显萎缩，坏死区逐步为纤维组织取代。对照组肝段呈不完全性凝固性坏死，范围较小。结论：ＴＨＡＥ－ＲＨＶＥ方法安全，能获得选择性肝叶（段）切除的效果，可用于单发性巨块型肝癌的治疗。     

经导管血管内栓塞治疗肝动脉假性动脉瘤的疗效观察

目的 评价血管内栓塞治疗肝动脉假性动脉瘤(HAPA)的疗效和对肝功能的影响.资料与方法 8例HAPA患者行选择性腹腔动脉造影明确动脉瘤的部位后,再超选择至载瘤动脉进行血管内栓塞治疗.栓塞术后随访3～60个月,观察临床和肝功能情况.结果 8例血管造影均明确诊断.其中肝外型4例,肝内型4例;7例用弹簧圈或微弹簧圈栓塞,1例单纯明胶海绵颗粒栓塞.栓塞术后造影复查8例HAPA均消失.动脉瘤破裂出血患者出血均停止.阻塞性黄疸的患者术后1周黄疸消褪.1例单纯明胶海绵颗粒栓塞者术后3天出血复发;7例钢圈栓塞者无出血和HAPA复发,影像学复查4例HAPA消失,3例HAPA缩小、机化.肝功能检查,2例转氨酶一过性轻度升高[谷-草转氨酶(AST)达286 U/L,谷-丙转氨酶(ALT)达103 U/L)],2例栓塞前肝功能异常栓塞后1周恢复正常;余4例肝功能无异常改变.结论 弹簧圈血管内栓塞治疗HAPA疗效好、并发症少.选择性肝动脉弹簧圈栓塞,对肝功能无明显影响.     

白芨微球与无水乙醇行兔门静脉栓塞的实验研究

目的　探讨门静脉栓塞的安全范围及白芨微球作为门静脉栓塞剂的可行性与有效性。材料与方法　新西兰大白兔 30只 ,随机分为两组 ,分别以白芨微球和无水乙醇行兔门静脉不同分支栓塞治疗 ;栓塞后行连续随访2 8d ,定期复查肝功能、CT、门静脉造影及动物处死后组织病理检查等 ,并将所获的数据行统计学处理。结果　术后丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)变化较明显 ,术后第 1d开始增高 ,术后 5d达到最高峰 ,白芨微球组显著高于无水乙醇组 (P <0 .0 5 ) ,但两组均于栓塞后 14d逐步恢复正常。栓塞部位比较 :两组均以右上支加左内支栓塞小组增高最为明显 ,且均有 1只兔于术后 14d死亡。 2种栓塞剂均可导致门静脉段及段以下分支完全性、急性闭塞 ,邻近的门静脉分支未见异位栓塞 ;无水乙醇栓塞后 2 8d ,肝实质呈不规则散在液化坏死 ,部分栓塞的门静脉出现再通现象 ;而白芨微球栓塞后 ,肝实质呈大片状气化坏死 ,未见栓塞区门静脉再通 ;两组术后再通率与不全坏死率有显著性差异 (P <0 .0 5 )。结论　门静脉栓塞的安全性与栓塞范围密切相关 ,其安全范围应小于或等于 3个段 ;白芨微球可作为一种末梢性门静脉栓塞剂 ,其安全性与无水乙醇相似 ,但栓塞效果佳 ,值得进一步临床应用与推广。     

外磁场控制磁性明胶微球肝动脉栓塞的实验研究

本实验随机使用杂种犬１７只。磁性明胶微球（ＭＧ－ｍｓ）粒径１０～３０μｍ。含ｘ－Ｆｅ＿２Ｏ＿３３０％（Ｗ／Ｗ）。血管造影、放射性核素扫描、ＣＴ扫描以及病理组织学检查，均显示出磁性明胶微球通过外磁场导向控制，在肝动脉内具有明显的靶向栓塞作用。栓塞术后，血清ＡＬＴ、ＡＳＴ、ＡＬＰ短时间内升高，２～３天达高峰，尔后下降，于３～４周内恢复到术前水平。末发现不良反应及异位栓塞。     

丹参酮ⅡA-聚乳酸/羟基乙酸微球对兔肝动脉栓塞作用的研究

目的 观察经肝动脉注入丹参酮ⅡA-聚乳酸/羟基乙酸微球对兔肝动脉的栓塞作用.方法　新西兰兔24只在DSA监视下经肝动脉注入丹参酮ⅡA微球,注入后10 min,1、3、7、14、21、30、42 d各取3只再次造影,观察肝动脉栓塞情况,并处死取肝、心、脾、肺、肾和胃组织,观察病理变化,同时作血常规和肝、肾功能检查.结果 栓塞后10min造影显示,肝动脉末梢血管消失.栓塞后第1、3、7、14、21、30 d造影,肝动脉末梢血管均未显影.栓塞后第42 d造影显示肝动脉末梢血管已显影.病理切片显示栓塞部位出现炎性及坏死.常规和生化结果:介入栓塞后白细胞出现一过性升高,第7 d恢复正常水平(P＞0.05);AST、ALT均在栓塞后第3 d达到最高值,第7 d恢复正常水平(P＞0.05).结论 丹参酮ⅡA微球具有良好的肝动脉末梢栓塞效果,栓塞时间在30～42 d,是一种理想的肿瘤介入栓塞剂.     

国产PVA微球肝动脉栓塞的实验研究

Polyvinyl alcohol microsphere impregnated with barium sulfate was found to be a good embolizing agent in regard to shape, suspension and distribution in the arteries. Different-phase hepatic artery embolization with microspheres (50 approximately 100 microns, 100 approximately 300 microns) was performed in 20 dogs to evaluate the angiographic and histopathologic changes and hepatic function alterations. Permanent occlusion of the peripheral arterioles was observed on follow-up angiograms one week to six months after embolization. Shrinkage of the embolized segment and focal infarct of the liver were noticed in nearly half of the specimens both grossly and microscopically. The shape and structure of the microspheres were seen unchanged on different-phase specimens, and microspheres as small as 50 microns could reach the corresponding small peripheral arterioles. The liver function alterations were comparable with gelfoam embolization. This study suggested that permanent embolization of small arterioles was possible with such microspheres.     

Development of collateral circulation following distal embolization of hepatic artery in pigs

The distal hepatic artery was embolized with black polystyrene microspheres (diameters of 50±10 μ and 200±25 μ) in 12 pigs. The animals were reexamined from 1 h to 2 weeks after embolization via hepatic angiography and subsequent injection of Microfil, a silicone rubber compound, into the arterial and portal vascular systems of the liver. Dissection of dehydrated and cleared liver specimens under the stereomicroscope demonstrated the presence of arterial collaterals bypassing embolized vessels within 2–3 days after embolization. Collaterals were noted to develope around occlusions in arteries with inner diameters as small as 100 μ.     

肝动脉栓塞后肝功能改变及病理基础

目的：探讨单纯全肝动脉末梢栓塞对正常肝组织的影响。方法：用５０～１００ｕｍ明胶海棉微球末梢栓塞１０条犬的全肝动脉，栓后１、３、７、１４和２８ｄ，分别处死１或２条犬，观察组织病理改变，处死前抽血化验肝功能，动态观察肝功能的变化及相应的病理改变。结果：栓后１ｄＧＰＴ、ＧＯＴ及ＡＫＰ升高，超过正常值范围，肝细胞变性、坏死。栓后３ｄＧＰＴ、ＧＯＴ升至高峰，肝细胞变性严重，坏死明显。然后下降，２周后恢复。结论：肝动脉栓塞对肝细胞的急性损害是暂时的     

血余炭栓塞狗肾动脉病理改变的初步研究

目的：观察中药血余炭栓塞狗肾动脉的病理改变，为临床提供实验依据。方法：将中药血余炭磨制成200-500μm大小的颗粒，超选栓塞部分末梢动脉血管。栓塞术后第7、14和56天分别处死1、2和3号犬，取出双肾固定，制作病理标本。结果：栓塞术后第7天，肉眼见栓塞部分肾脏缩小，切面末梢血管内有栓塞剂；镜下见血余炭栓塞剂附着于血管壁伴血栓形成。栓塞术后第14天，炎性反应明显，并有少量出血，血管壁炎性坏死，血栓逐渐机化。栓塞术后第56天见栓塞部分肾脏明显缩小，有大面积的缺血性梗死；镜下见血栓完全机化，栓塞组织呈缺血性梗死，栓塞血管有少量再通。结论：血余炭栓塞的病理过程为：血余炭附着血管壁，诱发血栓形成，血栓机化，血管壁炎性坏死，管腔闭塞，栓塞组织缺血性梗死，栓塞血管少量可再通。     

A Water-Based Liquid Embolic: Evaluation of its Safety and Efficacy in a Rabbit Kidney Model

PurposeTo evaluate a novel aqueous-based liquid embolic (Embrace Hydrogel Embolic System, [HES]) that has been developed to embolize hypervascular tumors by filling the tumor vascular bed and solidifying into a hydrogel. HES was evaluated for embolization safety and efficacy relative to microspheres in a preclinical rabbit kidney model.Materials and MethodsA renal embolization model in New Zealand white rabbits was utilized. Twenty-four rabbits underwent unilateral kidney embolization via the main renal artery with either HES or 40-μm microspheres. Twenty-two rabbits survived the procedure and were monitored for 2, 12, 17.5, or 26 weeks before sacrifice. All rabbits underwent a repeat renal angiogram before necropsy. HES was evaluated for nontarget embolization, safety, and embolization effectiveness as measured by recanalization and viability of embolized tissue.ResultsBoth embolization materials were found to be safe, with targeted tissue necrosis and absence of nontarget embolization. Prenecropsy angiograms found vascular recanalization in 0/14 (0%) HES-embolized kidneys and in 3/8 (38%) microsphere-embolized kidneys (P = .036). Viable kidney tissue was observed in 2/14 (14%) kidneys embolized with HES and 5/8 (63%) kidneys embolized with microspheres (P = .052). All kidneys embolized with microspheres that showed vascular recanalization had viable tissue on histological sections. HES was observed in vessels as small as 10 μm in diameter in histological analysis.ConclusionsHES provided deep, durable vascular bed embolization that resulted in less recanalization and, on an average, less viable target tissue compared with 40-μm microspheres. No systemic effects or nontarget tissue embolization was identified.     

Chitin-based embolic materials in the renal artery of rabbits: pathologic evaluation of an absorbable particulate agent

PURPOSE: To prospectively evaluate the tissue reaction to and the embolic effect and absorption of chitin and chitosan microspheres and polyvinyl alcohol (PVA) in the renal artery of rabbits. MATERIALS AND METHODS: This experiment was performed in accordance with regulations on animal care and experiments. Thirty-six New Zealand white rabbits were divided into four groups according to the materials (PVA, chitin particles, and chitosan particles, and chitosan microspheres; diameter, 150-250 microm) used for embolization of the right renal artery. A rabbit from each group was sacrificed 1 and 3 days and 1, 2, 4, 8, 16, 24, and 32 weeks after embolization. Gross and microscopic pathologic findings were examined with hematoxylin-eosin, Masson trichrome, and Victoria blue staining. RESULTS: Gross pathologic findings were examined, and swelling of embolized kidneys was observed 1 and 3 days after embolization, whereas shrinkage of the embolized kidneys was consistently seen after 2 weeks, with a hard consistency and nodular surfaces being noted. At histologic analysis, chitosan microspheres filled the lumen more compactly than did other particles. With PVA, a large amount of capillary formations occurred within the embolized arteries, whereas chitin particles and chitosan microspheres showed a lower rate of capillary formation. The shape of all embolic materials remained intact until week 8, at which time the materials gradually decreased in size and number. The chitosan particles and the chitosan microspheres were absorbed around weeks 16 and 24, respectively. CONCLUSION: Chitosan microspheres have great potential as a new embolic material since they block blood vessels more compactly with a lower rate of capillary formation. This material is biocompatible, and it is absorbed 24 weeks after embolization.     

Identifying the Ideal Target Vessel Size for Bariatric Embolization: Histologic Analysis of Swine and Human Gastric Fundi

This study aimed to identify the ideal arteriole size to target in bariatric embolization, with the goal of maximizing weight loss efficacy while maintaining patient safety. Although all published clinical trials of bariatric embolization have used embolic microspheres that were at least 300 μm in diameter, optimal weight loss outcomes have been achieved safely in swine using 50-μm embolics. Human fundal remnants from bariatric surgery were compared with swine fundal sections after bariatric embolization with 50-μm embolic microspheres to assess the ideal fundal vessel size for bariatric embolization. In swine, the 50-μm embolic microspheres deposited in the luminal half of the submucosa with a mean arteriole size of 49 μm ± 30. The mean arteriole diameter in the corresponding submucosal layer of the human gastric fundi was 40 μm ± 30. These measurements may inform future clinical trials and direct the development of embolic agents for bariatric embolization.     

Transcatheter hepatic arterial embolization with avitene in dogs

The hepatic arteries in 36 dogs were embolized with microfibrillar collagen (Avitene) to evaluate the effects on the liver parenchyma. Serial examinations were then conducted over 4 weeks. The dogs were divided into 3 groups: Group 1 received Avitene soaked in saline, Group 2 received decanted Avitene, and Group 3 received Avitene decanted and filtered through gauze. Coagulation necrosis and degeneration of the liver parenchyma was noted in all 3 groups, but was least in Group 3. These results in dogs suggest that gauze filtration of Avitene prior to arterial embolization may also reduce damage to liver parenchyma.     

Changes in rat liver microcirculation after experimental hepatic arterial embolization: comparison of different embolic agents

PURPOSE: To evaluate the effects of hepatic arterial embolization on hepatic microcirculation in the rat liver by using different particulate agents. MATERIALS AND METHODS: Polylactic acid microspheres, polyvinyl alcohol particles, and absorbable gelatin powder were injected into the hepatic artery of 50 rats. Saline was used as the control agent. Flow characteristics of hepatic microcirculation were qualitatively assessed on days 0 and 7 after embolization by using in vivo microscopy. Histologic specimens of the rat liver were analyzed. RESULTS: The polylactic acid (1-5 microns) injected into the hepatic artery was seen circulating through the sinusoids into the central venules. The slowing of flow observed with the injection of larger (50-200-micron) particles reflected the arterial occlusion occurring more proximally. After 7 days, all embolic agents caused vascular occlusion that led to necrosis and fibrosis. Networks of irregular, high-speed vessels that resembled arterioles and bypassed the normal sinusoids were observed. CONCLUSION: The necrotic areas observed after experimental distal occlusion of the hepatic arteries in the rats were bypassed by vessels similar to the capillarized sinusoids observed in the cirrhotic liver in humans. These vessels acted as sinusoidal shunts in the embolized territories.     

Experimental studies of intrahepatic portal vein embolization and embolic materials

The author has developed the intrahepatic portal vein embolization for the treatment of liver cancers. The purposes of this new method are 1) extension of indications for surgery by causing compensatory hypertrophy of non-embolized lobe, 2) prevention of dissemination of the tumor cells via the portal vein, 3) causing complete ischemic necrosis of the tumor together with arterial embolization, and 4) blockade of centripetal extension of tumor thrombus. The feasibility and safety of this method were studied experimentally. Three kings of materials were prepared for embolization of the portal vein; a Lipiodol-thrombin mixture (Lp-T), a Lipiodol-fibrin adhesive mixture (Lp-F), and a mixture of Lipiodol with isobutyl-2-cyanoacrylate (Lp-IBC). The portal vein was embolized in 31 dogs, 6 with Lp-T, 14 with Lp-F, and 11 with Lp-IBC. Lp-F was used 30 to 90 seconds after preparation, which had been found to be best in an in vitro study. Lp-T and Lp-IBC could be used at any time after preparation. Embolization was done safely and reliably, except in two cases of Lp-F, by use of a balloon catheter for Lp-T or Lp-F and a coaxial catheter for Lp-IBC. Follow-up portography showed recanalization in one week in the dogs embolized with Lp-T. The obstruction was maintained for two to four weeks in the dogs embolized with Lp-F, and for four weeks in all dogs embolized with Lp-IBC. Damage in the liver was slight both macroscopically and histologically. Changes in liver function and elevation of the pressure of the portal vein were transient. The author concluded that the intrahepatic portal vein embolization was both feasible and safe when the materials tested were used, and could be an effective method for liver cancers. In clinical cases, Lp-T would be suitable for short-term occlusion, Lp-F for a moderate term, and Lp-IBC for long-term. The material should be selected with regard to the purpose.