A Modified Human Ureter Graft Tanned by a New Crosslinking Agent Polyepoxy Compound for Small Diameter Arterial Substitutions: An Experimental Preliminary Study

The effectiveness of human ureter grafts tanned by polyepoxy compound for small diameter arterial substitution was examined in 8 carotid arteries of rabbits, followed by an observation period of either 1 month (n = 6) or 6 months (n = 2). In this model there was no evidence of rejection, aneurysm formation, or infection. The modified human ureter showed excellent patency in all cases as well as excellent function, and the histological evaluation revealed monolayer endothelial-like cells covering all of the surface of the graft as was expected. No intimal hyperplasia was demonstrated at either anastomotic site. This study suggests that our newly designed polyepoxy compound fixed human ureter could serve as a satisfactory blood conduit with good long-term patency for substitution.     

内皮化环氧交联牛心包材料动物体内抗钙化的研究

目的研究生物材料内皮化延缓钙化的效果，从材料学上改进生物瓣性能，以提高其耐久性。方法将环氧交联的牛心包材料体外内皮化后同时进行犬股动脉间位移植和腹部皮下包埋，与单纯戊二醛处理者和单纯环氧处理者进行钙化程度对比。结果钙含量测试结果以内皮化环氧交联材料皮下包埋最低，未内皮化材料中以环氧处理者钙含量较低。结论环氧交联牛心包材料可实现体外快速内皮化，生物材料的内皮化“活化”有赖于表面全部被自体存活内皮细胞覆盖才能实现，完全的内皮化确有抗钙化作用，用两种动物模型研究生物材料抗钙化和内皮化时各有优缺点     

In Vitro and In Vivo Characterization of a Silk Fibroin‐Coated Polyester Vascular Prosthesis

Silk fibroin (SF) is well known to be biocompatible, degradable, and nontoxic. In this study, SF was impregnated into a porous polyester graft (InterVascular external velour, InterVascular, Inc., La Ciotat, France), 8 mm in diameter. The SF‐impregnated graft was investigated in vitro and in vivo to evaluate its potential for use as a new vascular graft impervious to blood, while retaining high porosity for tissue ingrowth and biological healing. For in vitro investigation, the water permeability, coating weight, morphology, and mechanical properties of the SF‐impregnated grafts were compared with collagen‐coated grafts (InterGard grafts, InterVascular, Inc.). The water permeability of the controls (1388 ± 30.5 mL/cm²/min at 120 mm Hg) was reduced >99% by SF impregnation, rendering the graft impervious to blood. The coating weight of the collagen was 117 ± 22 mg/g of graft, producing a slightly lower value than the InterGard prosthesis (302 ± 23 mg/g). For the in vivo experiment, six SF‐sealed vascular grafts were implanted in the abdominal aorta of dogs for scheduled periods ranging from 4 h to 6 months. Commercial collagen‐impregnated grafts (InterGard) and untreated external velour grafts (InterVascular) were also implanted for scheduled periods ranging from 1 to 6 months for comparison. Gross observation of the explanted grafts and histological examination of the representative sections were conducted for two types of grafts using a light microscope after hematoxylin–eosin staining. These SF‐impregnated grafts showed less foreign body and inflammation reactions, and the SF layer was almost completely absorbed. The average of the values in each period for the SF grafts was 48% neointima at 1 month, 85% at 3 months, and 97% at 6 months, whereas those of the InterGard prostheses was 34, 46, and 90%, respectively. This study demonstrated that the use of a biodegradable SF as biological sealant can be a feasible approach to prepare impervious textile arterial prostheses. The SF‐impregnated graft showed less thrombogenesis and induced host cell migration along the matrix without foreign body or inflammatory reactions. Moreover, it appears to facilitate the development of endothelial‐like cells.     

环氧交联去细胞牛颈静脉带瓣管道的血液相容性实验研究

目的评价环氧化合物（PC）交联去细胞牛颈静脉带瓣管道（BJVC）的血液相容性,探讨其在心血管外科和组织工程中的应用前景。方法选取本地健康杂种犬20只,采用随机数字表法分为实验组（n=10）和对照组（n=10）。实验组用PC交联的去细胞BJVC,对照组采用戊二醛（GA）交联的BJVC。运用兔血进行体外溶血实验计算溶血率,绘制时间-吸光度曲线;采用人全血测定D-二聚体和补体C3a des Arg水平评价其体外血液相容性。采用PC和GA制备的BJVC重建犬右心室-肺动脉连接,两组犬饲养10个月后,观察有无血栓形成评价其体内血液相容性。结果实验组溶血率（0.23%）低于对照组（0.35%）,符合医用生物材料的国家标准（〈5%）。实验组的凝血时间曲线较对照组平缓。实验组D-二聚体水平低于对照组,两组差异有统计学意义（0.10±0.01μg/ml vs.0.12±0.02μg/ml,t=3.277,P=0.004）,但均在正常范围内。实验组补体C3a des Arg水平低于对照组,两组差异有统计学意义（0.74±0.09μg/ml vs.1.02±0.19μg/ml,t=4.183,P=0.001）。犬右心室-肺动脉连接重建术后10个月每组各有8只生存,各有2只死于心室颤动。对照组3例有血栓形成,实验组无血栓形成。结论与GA交联相比,PC交联的BJVC体外、体内血液相容性均具优势,临床应用前景良好。     

Vascular Prostheses Performance Assessment of Vascular Prosthesis Failure

During 30 years of active participation in clinical vascular surgery and the screening and development of vascular prostheses, greater than 450 different fabrications have been evaluated. Vascular prosthesis retrieval and analysis during this period of time have been systematized, and greater than 40 different causes of failure of vascular prostheses have been classified into six classes: failure of diagnosis, error of implantation, patient contribution, complications of healing, fabrication failure, and infection. Such analyses allow for scientific evaluation, testing development, and the elaboration of performance standards so badly needed at present. Such a task is being organized by American Society for Testing and Materials (ASTM) Subcommittee F04.04 on Cardiovascular Materials and Devices and will require the active participation of all knowledgeable individuals.     

Experience with the Hemasite Vascular Prosthesis

A 3-year experience with the no-needle vascular prosthesis Hemasite, implanted in 10 patients who underwent hemodialysis and have a long history of multiple vascular access failures, is described. During 182 months of follow-up study, 30 thromboses occurred, while nine of 10 patients did not receive any antiplatelet aggregant treatment. Hemasite was declotted 12 times with a local infusion of urokinase and 12 more times by thrombectomy. A surgical procedure was performed only in the other cases, and the rate of surgical intervention fell from 0.18 interventions per patient per month before Hemasite implantation to 0.027 after implantation.     

Unusual Inflammatory Responses around a Collagen-Impregnated Vascular Prosthesis

Abstract: A collagen-impregnated graft, called Hemashield, has been used clinically; however, some complications such as pyrexia, fluid accumulation, and unusual scar formation around the graft have been reported. To understand the cause of these problems, the graft was examined both in vivo and in vitro. Endotoxin and (1–3)β-d -glucan were detected in the extract from Hemashield by special quantative methods called Toxicolor and Endospecy. In an animal study, the grafts were implanted in the thoracic descending aorta of 9 dogs and were designed to explant at 2 weeks. Macroscopic evaluation of the explants showed that the graft had no infection, but fluid accumulation was found in the pleural cavity and around the graft-like seroma. Microscopical observations revealed that neither fibroblasts nor capillary blood vessels had infiltrated in the adventitial side of the graft, but numerous plasma cells, lymphocytes, and macrophages were noticed. The impregnated collagen was partially absorbed. These results indicate that the graft had some contaminants which contained a certain amount of endotoxin and (1–3)β-d -glucan, resulting in noninfective inflammatory responses around the graft.     

Evaluation of a polyepoxy compound fixed biological vascular prosthesis and an expanded polytetrafluoroethylene vascular graft

Antithrombogenicity is one essential requirement for the successful use of small caliber vascular prostheses. In this study, a polyepoxy compound fixed, heparinized 4 mm diameter Baxter Denaflex vascular graft was evaluated against a 4 mm diameter Gore-Tex expanded polytetrafluoroethylene (ePTFE) vascular graft in the canine model. In addition to the thromboresistant characteristic conferred by heparinization, the crosslinking agent allowed the Denaflex graft to retain the original color of the native artery. Six centimeter long graft segments were implanted into the carotid arteries bilaterally in 5 dogs. The patency rate at 3 months for the Denaflex graft was 100% (five out of five) whereas in the control ePTFE graft, it was 40% (two out of five). The explanted Denaflex grafts exhibited softness and flexibility, and their luminal surfaces maintained a white color like that before implantation. To the contrary, the patent ePTFE grafts felt hard, and red thrombi covered large portions on their inner surfaces. Under microscopic observation, neointima formation was limited to regions near the anastomotic sites for both types of grafts. This experiment showed that the Denaflex vascular graft has an excellent antithrombogenic property and has a compliance similar to native arteries.     

The Effects of Losartan in Preserving the Structural Integrity of Decellularized Small Diameter Vascular Allograft Conduit Implants In Vivo

Decellularization is a proposed method of preparing nonautologous biological arterial vascular scaffolding; however, the fate of the supporting medial elastic fiber, which is important in preserving the vascular structural integrity, is uncertain. The influence of losartan on preserving the medial elastic fiber integrity in decellularized small diameter vascular conduits (SDVC) was investigated. Decellularized infrarenal abdominal aortic allografts were implanted in Sprague‐Dawley rats treated either with (study rats, n = 6) or without oral losartan (control rats, n = 6) and graded 8 weeks later according to a remodeling scoring system (1‐mild, 2‐moderate, 3‐severe) which we devised based on the intimal hyperplasia degree, morphologic changes, and elastic fiber fragmentation of the conduits. DAPI immunohistochemistry analysis was performed in 47 (25 decellularization only and 22 losartan treatment) cross‐sectional slide specimens. The losartan versus decellularization only SDVC showed a significantly lower medial elastic fragmentation score (1.32 vs. 2.24, P < 0.001), superior medial layer preservation, and relatively more normal appearing intimal cellular morphology. The results suggested rats receiving decellularized SDVCs treated with losartan may yield superior medial layer elastic fiber preservation.     

人工颈椎间盘假体体外功能试验方法及评价策略

人工颈椎间盘置换术保留了相邻椎体节段的运动功能,减少了相邻节段的应力水平,有利于防止术后邻近节段发生退变。目前,国内应用的人工颈椎间盘假体主要是进口产品,国产同类产品大多处于研发生产过程中。本文通过介绍人工颈椎间盘假体的体外功能评价方法,包括假体沉陷、蠕变、推出、半脱位试验,以及动静态压缩、剪切试验和磨损试验等,结合人体颈椎的生物力学数据,以评价产品临床使用的安全性和有效性;基于FDA关于人工颈椎间盘假体的公开数据,对5种不同设计的人工颈椎间盘假体体外功能性试验结果进行分析比较,探讨人工椎间盘假体体外评价试验的可接受依据,为国产同类产品的研发提供参考。     

The Superiority of Hollow Fiber Membrane over Bubble Oxygenator in a Perfusion Circuit for the Evaluation of Small Caliber Endothelialized Arterial Prostheses

Abstract: A perfusion circuit was constructed from a pneumatic ventricular assist device, 2 compliance chambers, 4 small-diameter silicone tubes (ID 4 mm) simulating shear inducing vascular prostheses, and an oxygenator with a heat exchanger. A bubble oxygenator (in a BO circuit) and a hollow fiber membrane oxygenator (in an MO circuit) were studied. The circuits were perfused with 30% human serum containing culture medium for 7 days at 37^oC. The pH, Po₂, Pco₂, Na⁺, K ⁺, Ca^{2 +}, CI^-, glucose, and total protein concentrations remained the same in BO and MO circuits during the 7 days of perfusion. The differences between the values measured in the perfusion medium and in the medium maintained in the static conditions of cell culture were not significant. In the BO circuit, the amount of cholesterol and triglyceride concentrations decreased whereas the relative amounts of albumin, α1, α2, p, and γ globulins remained stable in the perfusion medium. The medium from the BO circuit did not promote the proliferation of cultured human saphenous vein endothelial cells. In the medium from the MO circuit, the cholesterol and triglyceride concentrations did not change with perfusion time; the proliferation rate and anticoagulant function of endothelial cells were maintained. The hollow fiber membrane oxygenator preserves the biological characteristics of the cell culture medium in a perfusion circuit. The MO circuit permits the performance of relevant studies on shear stress resistance and functional activity of human endothelial cells seeded onto vascular prostheses.     

Rabbit Model for Evaluation of a Long Small-Caliber Vascular Graft

We developed an experimental method for evaluating the properties and healing process of a long, small-caliber vascular graft in a small animal. Eight rabbits were used. A left thoracotomy was performed and the thoracic aorta was isolated. The aorta was clamped and excised in the middle without a temporary shunt. A 15-cm-long by 4.0-mm-ID segment of a vascular graft was implanted end to end. After the blood flow of the aorta was restarted, the long graft remained in a big loop shape in the thoracic cavity and showed no tension. The major advantage of this technique is that, although it is simple, we are still able to evaluate a long, small-caliber vascular graft in a small animal.     

In Vivo Evaluation of the Effects of a New Ice-Free Cryopreservation Process on Autologous Vascular Grafts

John B. Murphy (1857–1916), one of the most outstanding and controversial surgeons of his age, was a product of the strong clinical programs that developed in Chicago in the late 19th century. Heavily influenced by Christian Fenger, surgeon and surgical pathologist, he went to Europe for training under Theodore Billroth and others. He applied results of his dog lab experiments to human problems while maintaining a large private practice. He is best known for his teaching clinics, for his groundbreaking work with a button for intestinal anastomosis, and for encouraging early operation in appendicitis. Though often in trouble with his fellow surgeons who accused him of stealing patients, especially in the Haymarket affair and when Theodore Roosevelt was shot, he nevertheless made many contributions to the care of surgical patients and development of academic surgery.     

Tissue Engineering of Small Diameter Vascular Grafts

Tissue engineering, using either polymer or biological based scaffolds, represents the newest approach to overcoming limitations of small diameter prosthetic vascular grafts. Their disadvantages include thromboembolism and thrombosis, anticoagulant related haemorrhage, compliance mismatch, neointimal hyperplasia, as well as aneurysm formation. This current review represents an overview about previous and contemporary studies in the field of artificial vascular conduits development regarding arterial and venous autografts, allografts, xenografts, alloplastic prostheses, and tissue engineering.     

In Vitro Activity and In Vivo Efficacy of Antimicrobial-coated Vascular Grafts

The serious medical consequences and costly management of infections associated with vascular grafts have prompted an expanding interest in examining the preventive efficacy of antimicrobial-coated vascular grafts. The purpose of antimicrobial coating of vascular grafts is to reduce bacterial colonization of the device and, hopefully, the occurrence of clinical infection. In this study we demonstrated that expanded-polytetrafluoroethylene vascular grafts coated with minocycline and rifampin provide broad-spectrum antimicrobial activity in vitro, as reflected by zones of inhibition, against Staphylococcus epidermidis, S. aureus, Enterococcus faecium, and Pseudomonas aeruginosa. We also showed in a rabbit model that subcutaneously placed minocycline/rifampin-coated vascular grafts have lower rates of staphylococcal device colonization (1/24 = 4% vs. 8/30 = 27%, p = 0.033) and device-related infection (0/24 = 0% vs. 6/30 = 20%, p = 0.028) than uncoated grafts. These promising results encourage the clinical evaluation of vascular grafts coated with minocycline and rifampin.     

In Vivo Evaluation of the Lillehei-Kaster Heart Valve Prosthesis

In vivo evaluation of the Lillehei-Kaster heart valve prosthesis was performed in 28 patients; 22 had undergone aortic valve replacement and 6 had had mitral valve replacement.Mean pressure gradients ranged from 6 to 53 mm Hg in aortic prostheses; valve area varied from 0.83 to 2.9 cm². The maximum opening angle of 80 degrees was never reached in this group of patients; opening angles ranged from 57 to 74 degrees without evidence of disc malfunction. There was no correlation between the ratio of effective to geometric valve area and the degree of opening of the disc occluder.Similar results were found in the mitral valve group. Gradients ranged from 6.0 to 12.5 mm Hg and valve area from 1.6 to 2.2 cm². The maximum opening angle was 59 to 63 degrees.It is concluded that incomplete opening of the disc occluder in pivoting-disc valves is not necessarily a sign of disc malfunction. Lillehei-Kaster valves smaller than 18 mm in internal diameter should be avoided in adults, and outflow aortoplasty for implantation of a larger prosthesis should be used in patients who have a narrow aortic root.     

复合带瓣人工血管替换升主动脉和主动脉瓣(24例报告)

报告２４例升主动脉瘤伴主动脉瓣关闭不全行升主动脉和主动脉瓣替换及冠状动脉开口移植术（Ｂｅｎｔａｌ术２２例，底盘法２例）。１３例伴有升主动脉夹层分离，对其中８例ＤｅＢａｋｅｙＩ型者，以Ｔｅｆｌｏｎ毡条内外加固主动脉切端后吻合。１３例用人工血管周围间隙与右心耳吻合以控制升主动脉吻合之外的出血。３例以人工血管片环包主动脉吻合口控制局部广泛渗血及出血。２例术毕不能脱离体外循环死亡，手术死亡率８３％。随访平均２１８个月，２例死于蛛网膜下腔出血，１例右股动脉栓塞经手术治愈；其余病人康复良好，心功能（ＮＹＨＡ）Ｉ～ＩＩ级。     

Acellular Endocardium as a Novel Biomaterial for the Intima of Tissue‐Engineered Small‐Caliber Vascular Grafts

We aimed to investigate whether acellular endocardium can be used as a useful biomaterial for the intima of engineered small‐caliber vascular grafts. Fresh endocardium was harvested from the swine left atrium and was decellularized by digestion with the decellularization solution of Triton X‐100 and SDS containing DNase I and RNase A. Surface morphological characteristics and Young's modulus were evaluated. To analyze the effect of mechanical characteristics on cell adhesion, the decellularized endocardium was stiffened with 2.5% glutaraldehyde. Small‐caliber vascular grafts were constructed using decellularized endocardium treated with or without glutaraldehyde as the intima. CD34+ cells were seeded onto the luminal surface of the vascular grafts and linked to bioreactors that simulate a pulsatile blood stream. Acellular endocardium had distinct surface morphological characteristics, which were quite different from those of other materials. The compliance of acellular endocardium was higher than that of other materials tested by Young's modulus. CD34+ cells formed a monolayer structure and adhered to the inner face of the acellular endocardium. The glutaraldehyde treatment stiffened the acellular endocardium but had little impact on the surface morphological characteristics or static adhesiveness of the cells. Data from the bioreactor study showed that the detachment of the cells from the surface of glutaraldehyde‐treated acellular endocardium increased dramatically when the pressure was equal or higher than 40 mm Hg, while the cells on the untreated acellular endocardium remained well and formed confluent monolayers and tight junctions under the same pressure. Acellular endocardium has distinct structures and mechanical characteristics that are beneficial for CD34+ cell adhesion and retention under dynamic fluid perfusion. Thus, it can be used as a useful biomaterial for the construction of the intima of engineered small‐caliber vascular grafts.     

人工血管移植治疗孤立性髂动脉瘤的手术探讨

目的探讨孤立性髂动脉瘤的手术治疗方法,包括复杂病理情况下动脉瘤切除、人工血管移植以及吻合口处理和缝合问题。方法回顾性总结1997年1月至2007年6月间收治的33例孤立性髂动脉瘤的临床资料,其中单侧髂动脉瘤29例,双侧4例。均在全身麻醉下行动脉瘤切除、人工血管移植血管重建术。结果4例双侧病变中,行主动脉-双侧股动脉人工血管移植1例,主动脉-双侧髂总动脉人工血管移植3例;29例单侧病变中,主动脉-髂总动脉人工血管移植1例,髂动脉-股动脉人工血管移植3例,髂总动脉-髂外动脉人工血管移植21例,髂总-髂总动脉转流4例。33例平均随访5（0.5-10）年。2例分别于术后3年和6年死于急性脑梗塞和心肌梗塞,1例术后2年死于交通事故,余健康存活,无复发,无吻合口狭窄或下肢缺血表现。结论动脉瘤切除人工血管移植是治疗孤立性髂动脉瘤的良好措施,仍然是目前医疗条件下有效治疗本病的主要手术方式。     

Adsorption of Basic Fibroblast Growth Factor onto Dacron Vascular Prosthesis and Its Biological Efficacy

Abstract: Adsorption of basic fibroblast growth factor (bFGF) onto a plain fabric Dacron vascular prosthesis (Micron, Intervascular Co., Ltd., Clearwater, FL, U.S.A.) and its release properties from the graft were examined using labeled bFGF, and its biological efficacy was evaluated in an animal study. In an in vitro study, 6 pieces of a Dacron graft were soaked in [¹²⁵I]-bFGF solution for 30 min. Then these pieces were soaked in 500 ml saline solution for 15 days, and the radioactivity of each piece was counted at various times. The initial amount of adsorbed bFGF was 2.48 ng/cm². At 24 h, 41% of the adsorbed bFGF was released and 59% remained. On the third day 55% remained, on the seventh day 52%, and on the 15th day 50% remained on the Dacron surface. Using the atmospheric glow discharge (APG) plasma treatment to render hydrophilic properties, no significant difference between plasma-treated grafts and non-plasma-treated grafts regarding the adsorption of bFGF was observed. In an in vivo study, 6 Dacron pieces adsorbed with bFGF were implanted in the subcutaneous layer of 2 dogs and removed 5 days after implantation. Six Dacron pieces without bFGF were also implanted as a control into the 2 dogs. Fibroblast migration with capillary ingrowth was observed in the specimens with bFGF compared to the controls. These results indicate that the simple adsorption of bFGF onto Dacron fabric is a useful method for the acceleration of host cell migration and capillary ingrowth into Dacron fabric vascular prostheses.