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Biomedical subjects

Y Marois

Publications and source records attributed to Y Marois.

At least 37 records · Page 2Linked to original sources

Characterization of abnormalities responsible for immediate rejection of porcine aortic valves for the manufacture of bioprostheses.

Gross observation at the slaughterhouse determines the primary selection of porcine aortic valves for the manufacture of bioprostheses. This step is critical because only valves with significant abnormalities are rejected. The present study validated this selection process by investigating the pathological characteristics of one series of accepted valves and one series of rejected valves. Macroscopy, x-ray examination, light microscopy, and scanning electron microscopy (SEM) were performed on 5 initially rejected valves, 3 leaflets from 3 other initially rejected valves, and 6 valves that successfully passed this first step in the selection process. Abnormalities were macroscopically visible only on the rejected valves and were described as thick white areas, heavy white striations, thin spots, white plaques, and nodules. Individual variability in the structure of each leaflet was more significant in the rejected valves than in the valves that had passed the first inspection. The leaflets of the rejected valves were also irregularly thick with a lack of consistency in the position and prominence of the different layers. The formation of nodules and the presence of white plaques in the inner fibrosa layer were among the pathological features. The initially accepted valves considered defect free under gross observation continued to display some weaknesses, and not all of the valves selected during the first step of the process were suitable to become bioprostheses. Because the manufacturer carries out further quality control inspections at every step of preparation resulting in additional rejections, it is therefore anticipated that all valves with defects will be rejected. None of the rejected valves were defect free, and rejection was fully justified.

Animals↗

In vitro and in vivo studies of a polyester arterial prosthesis with a warp-knitted sharkskin structure.

The present study was undertaken to assess the performance of a new knitted and gelatin-sealed polyester vascular graft that is believed to have greater dimensional stability than current commercial devices. Samples of the uncrimped, crimped, and sealed prosthesis were submitted to a series of in vitro and in vivo trials. Four commercial polyester knitted devices were included as controls for the in vitro tests, which included measurements of the textile and yarn structure and physical, chemical, and thermal properties of the graft, such as water permeability, dilatation, suture retention strength, melting point, and crystallinity index. The in vivo evaluation involved implanting the prototype device as a canine thoraco-abdominal bypass for periods ranging from 4 h to 1 year and assessing the biocompatibility, biofunctionality, and biostability of the explanted specimens. The warp-knitted structure of the prototype device has a unique sharkskin stitch that confers a superior dilatation resistance and suture retention strength to the prosthesis. The animal trial demonstrated that the gelatin ensures initial hemostasis without preclotting. The gelatin is bioresorbed during the first 2 weeks of implantation, which generates a temporary, moderate, acute inflammatory response. An external capsule of granulomatous tissue and an internal collagen capsule are formed between the first and third month. Analysis of the textile and physical properties of the explanted prostheses confirmed there was neither dilatation nor significant changes in structure or mechanical performance during implantation, thus confirming the biostability of this new prototype device and opening the way for clinical trials.

Anastomosis, Surgical↗

The Dialine II graft: a new collagen-impregnated warp-knitted polyester arterial prosthesis.

The Dialine graft, a new prototype of knitted vascular prosthesis that uses a different brand of polyester fibers as an alternative to Dacron fibers, has been shown to offer excellent in vitro physical performance and in vivo healing. Although it still requires preclotting, the Dialine prosthesis was made impervious by impregnation of bovine type I collagen cross-linked with vapors of formalin. The purpose of the present investigation was to compare the in vitro physical characteristics of the Dialine II graft with those of the collagen-impregnated Hemashield graft. In addition, we studied the healing performance as a thoracoabdominal bypass in dogs for prescheduled periods of implantation ranging from 4 hours to 6 months. In vitro, the bursting strength, resistance to dilatation, and suture retention strength properties of the Dialine II prosthesis were all shown to exceed those of the Hemashield control graft. In the first weeks after implantation, the Dialine II grafts induced a discrete inflammatory response, as shown by the constant leukocyte counts observed both before implantation and when the animals were killed, as well as by the histologic observation of a few inflammatory cells in contact with the collagen. Consequently, the Dialine II grafts showed a slow rate of bioresorption of cross-linked collagen. At 1 month, a thin internal collagenous capsule was present at both anastomoses, laying over the original collagen coating. At 3 and 6 months, areas of thrombotic deposits and endothelialized areas were observed on the luminal surface. Because results of early clinical trials have been highly satisfactory, this prosthesis may be recommended for use without restriction as a medium- and large-diameter blood conduit.

Animals↗

Vascugraft polyurethane arterial prosthesis as femoro-popliteal and femoro-peroneal bypasses in humans: pathological, structural and chemical analyses of four excised grafts.

Following positive results obtained in in vitro studies and in vivo implantations in animals, a clinical trial using the Vascugraft polyurethane arterial prosthesis as a below-knee substitute was undertaken in 15 patients. Eight grafts became occluded during the first year, and segments from four of them were explanted and made available for pathological, structural and chemical investigations. The implantation periods ranged from 21 to 358 days. Failures were associated with kinking (one case), possible anastomotic mismatch between the graft and the artery (one case), and poor run-off (two cases). No organized collagenous internal encapsulation was noted; however, endothelial-like cells were observed at the anastomotic site of one graft. No significant structural degradation of the prostheses was observed in those grafts implanted for 21, 38 and 46 days. Some deteriorations in the fibrous structure were observed on the external surface of the prosthesis implanted for 358 days. High-resolution carbon C1s analysis by ESCA demonstrated a 60 to 80% decrease in carbonate content on the surface of all explanted prostheses. Chemical analyses of each polyurethane graft by IR, SEC and DSC revealed no significant chemical changes. The clinical performance of the Vascugraft prosthesis for below-knee implantation proved to be no more impressive than that of expanded polytetrafluorethylene, the currently accepted reference. The decision by B. Braun Melsungen AG to end this program is therefore to be regarded as highly professional.

Aged↗

Shelf-life of bioprosthetic heart valves: a structural and mechanical study.

This study was undertaken to evaluate the influence of storage conditions on the shelf-life of porcine bioprosthetic valves. Fifty-five unimplanted porcine bioprostheses have been evaluated. The valves were stored in 0.5% buffered glutaraldehyde solution for different periods of time (7, 23 and 32 months). Twenty-eight valves were refrigerated while the remaining valves were stored at room temperature. The pH of the glutaraldehyde solution at room temperature decreased with time of storage, while that kept in the refrigerator remained stable over the course of the study. Macroscopic observations showed that the valve tissues kept at room temperature, especially for the periods of 23 and 32 months, became darker and more yellow in colour, whereas the refrigerated specimens exhibited no such changes in appearance. Scanning electron microscopy analysis revealed no noticeable differences on the surfaces of the leaflets stored under different conditions. Mechanical tests, including stress-strain response, stress relaxation and fracture behaviour, were carried out. Analysis of variance showed that the storage temperature, but not the length of storage, had a significant effect on some mechanical properties. The stress relaxation at 1000 s (P = 0.05), the ultimate tensile strength (P = 0.01) and the strain at fracture (P = 0.04) were all higher after storage at room temperature compared to the results after refrigeration. No statistically significant changes in the denaturation temperature of the collagen were observed between the different storage conditions. In conclusion, the storage temperature appears to have some influence on the bioprosthetic tissue. The bioprostheses stored under ambient conditions experience changes which may influence their longterm in vivo performance.

Animals↗

Arterial wall mechanical characteristics after treatment in collagenase: an in vitro aneurysm model.

OBJECTIVE: To investigate the mechanical characteristics of canine aortas treated with buffered collagenase as a first step in developing an animal model of aortic aneurysm for the validation of stent-grafts. DESIGN: In vitro study of canine aortas. INTERVENTIONS: Canine thoraco-abdominal arteries were divided into the descending thoracic aorta the suprarenal artery and the infrarenal artery; these segments were incubated separately in a buffered collagenase solution for 1 to 6 hours. Some segments were left untreated as controls. OUTCOME MEASURES: Mean arterial wall thickness, measured with Vernier callipers and computerized histomorphometric methods and longitudinal tensile strength of control and treated vessel segments. RESULTS: The arterial wall thickness decreased with incubation time. After 1 hour of incubation the reduction was approximately 15% for the descending thoracic aorta, 16% for the suprarenal artery and 18% for the infrarenal artery. After 6 hours the total reduction in wall thickness was 32%, 41% and 44% respectively for the 3 segments. The tensile strength of the treated arterial segments also decreased with the incubation period. Initially, the infrarenal segment displayed the greatest strength; however, this was reversed as the period of incubation increased. The inelastic limit of the descending thoracic aorta control segment was reached at 100% elongation, whereas that of the suprarenal artery was reached at 80% and that of the infrarenal artery was reached at 60% elongation. All of the arterial segments became weaker as the period of incubation in buffered collagenase increased. CONCLUSION: This in vitro incubation technique successfully altered the structure of the collagen fibre network within the arterial wall. This method may be an option in developing an aneurysm model to test stent-grafts in vivo.

Aneurysm↗

In vitro characterization of a fluoropassivated gelatin-impregnated polyester mesh for hernia repair.

The surgical management of abdominal hernias requires prosthetic grafting in situations where the defect is too large or the surrounding tissue is not available for repair. Flat patches made of different biomaterials have been used in textile or microporous forms. The present work describes the results of an in vitro study comparing the morphological, mechanical, and chemical characteristics of a new textile prototype, Fluoropassiv, made of polyester fibers treated with a fluoropolymer and impregnated with gelatin to those of seven existing commercial meshes and patches made from polypropylene, polyester, polytetrafluoroethylene (PTFE) yarns, and expanded microporous PTFE graft. The morphological study revealed a diversity of structures having a minimal relative porosity of 70%, high bursting, and suture retention strengths in comparison with natural muscular tissue. Elasticmoduli proved to depend more on the direction of the textile the rigidity was higher for those materials having tight structure, like the Fluoropassiv and the Surgipro meshes (> 30 MPa), whereas those with more open structures, such as the Marlex, Trelex, Lars, Bard Teflon, and GoreTex structures, showed lower elastic modulus (10 mPa). In addition, chemical analyses confirmed no irregularities in the polymers used in all prostheses and demonstrated that the fluoropolymer coating of the Fluoropassiv was uniformly distributed. The innovative aspects in the construction of the knitted fabric Fluoropassiv appears to make it suitable for repairing hernias, and the inclusion of both continuous fluoropolymer surface treatment of polyester fibers and gelatin impregnation appears to improve the healing process.

Biocompatible Materials↗

In vivo characterization of a fluoropassivated gelatin-impregnated polyester mesh for hernia repair.

The present study was undertaken to evaluate a new prototype mesh that consists of a knitted polyester structure treated with a fluoropolymer and impregnated with gelatin. The Fluoropassiv mesh, as well as two controls, the Surgipro polypropylene mesh and the Gore-Tex expanded polytetrafluoroethylene patch, were used for the repair of experimentally induced abdominal hernias in piglets and followed for scheduled implantation periods of 4, 15, and 60 days. At the sacrifice the mesh and surrounding tissue were excised for histological assessment of the healing sequence, for the identification of changes in hematologic and immunological characteristics, and for the measurement of the mechanical properties. After cleaning to remove the encroaching tissue, the explanted devices were monitored for biostability by infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The present study has demonstrated that the Fluoropassiv mesh provides adequate mechanical strength and compares favorably with the two controls. No exacerbated systemic or in situ hematologic or immunological reactions were observed with either the meshes of the patch material. Histological studies revealed that thick collagenous and vascularized tissue were well anchored to the three biomaterials as early as 15 days after implantation. The degree of tissue penetration differed depending on the device. Chemically, they proved stable over time.

Abdominal Muscles↗

Selecting valid in vitro biocompatibility tests that predict the in vivo healing response of synthetic vascular prostheses.

We have investigated the usefulness of six in vitro biocompatibility tests in predicting the healing performance of polyester vascular prostheses as observed in previous canine in vivo trials. Vascular grafts were evaluated by using (i) a direct contact (DC) assay, (ii) an extract dilution (ED) assay on murine fibroblast cells, (iii) a DC assay on endothelial cells, (iv) a complement activation study, (v) a leucocyte activation study of CD18 integrin subunit expression on human polymorphonuclear cells (PMNs) and (vi) interleukin-2 receptor expression on lymphocytes. Uncleaned polyester grafts had previously been associated with poor healing and gelatin-impregnated polyester grafts with delayed but satisfactory healing, whereas commercially cleaned polyester grafts had demonstrated excellent healing. Lightweight and heavyweight knitted and woven polyester grafts supplied specifically for this project were studied, each with a different surface condition, i.e. commercially available (CP), uncleaned (UP) and impregnated with gelatin (GP). The UP grafts induced fibroblast cytotoxicity according to the ED assay, poor migration and viability of endothelial cells, and an elevated expression of CD18 and interleukin-2 receptor on PMNs and lymphocytes, respectively. In contrast, the CP grafts promoted good endothelial cell growth, no evidence of cytotoxicity and a weaker cell activation, and the GP grafts were found to be non-cytotoxic, to exhibit a good cellular response and to moderate cell activation. The complement activation assay and the DC assay on fibroblasts were found to be less useful and less discriminating. From this, it is concluded that the two cell activation measurements, the DC assay on endothelial cells and ED assay on fibroblasts, are useful in predicting the in vivo healing response of arterial polyester substitutes.

Analysis of Variance↗

An albumin-coated polyester arterial graft: in vivo assessment of biocompatibility and healing characteristics.

The albumin-coated vascular graft (ACG) and its uncoated polyester substrate, the Vascular II (V-II), were evaluated in terms of biocompatibility and biofunctionality using two in vivo animal studies. Biocompatibility and immunoreactivity were assessed by implanting intraperitoneally in the rat small segments of the ACG and the V-II graft and harvesting them with their surrounding tissue 3d, 1, 2 and 4 weeks later. Cytofluorometric determination of total T cells (CD3), the ratio of CD4/CD8 subsets and the percentage of IL-2 receptor-positive T cells in the peripheral blood has revealed that no significant difference in any of the T cell populations was found between the ACG and the V-II graft. The cellular reactivity of the ACG in terms of acid phosphatase activity at the implant side was significantly greater at 3 d but not at longer periods. Biofunctionality was evaluated by implanting both grafts as a thoracoabdominal vascular bypass in dogs for 11 different periods ranging from 4 h to 6 months. The rate of albumin resorption was such that traces were still present at 1 month, but no longer observable at 2 months. Tissue incorporation into the graft wall was earlier for the V-II (2 weeks) than for the ACG (4 weeks), which showed complete encapsulation, tissue incorporation and endothelialization after 2 months in vivo. Only small differences were observed between both grafts in terms of platelet and fibrin uptake on the luminal surface. The prostacyclin/thromboxane A2 ratio increased to a level higher that 1.0 aorta within 1 month for the V-II and 4 months for the ACG. In conclusion, the Bard ACG has demonstrated excellent biocompatibility in terms of blood T cell behaviour and acid phosphatase activity at the implant site. Finally, its healing response is equivalent to that of the uncoated Dacron prosthesis once the albumin coating has been resorbed.

Acid Phosphatase↗

Efficiency of an external support to reduce lipid infiltration into venous grafts: in vitro evaluation.

Excessive distension of venous grafts due to arterial pressure enhances the convective water transport (filtration flow) through the vessel wall, and thus might affect the infiltration of macromolecules such as lipoproteins. In this paired experimental study, filtration velocities were measured at 100 mm Hg for canine jugular veins with or without external supports of expanded polytetrafluoroethylene (ePTFE) arterial prostheses. In addition, to assess the effect of filtration velocity on lipid infiltration or uptake, canine jugular veins were wrapped over half of their lengths with ePTFE arterial prostheses and perfused with dog serum containing 3H-cholesterol at a pressure of 100 mm Hg. At 100 mm Hg, the average filtration velocity of the wrapped jugular veins was 7.9 +/- 1.3 x 10(-6) cm/s whereas the average filtration velocity of the unwrapped veins was 27.3 +/- 2.7 x 10(-6) cm/s (p < 0.005). Moreover, the unwrapped veins had a significantly higher uptake rate of labeled cholesterol than the wrapped veins (10.9 +/- 7.3 x 10(-4) cm/h and 5.0 +/- 1.6 x 10(-4) cm/h, respectively, p < 0.005). In conclusion, under arterial pressure, veins experience excessive distention, which leads to significant increases in both filtration flow and cholesterol uptake. An external wrap or support of ePTFE material protects veins from excessive distension and thus may prevent atherosclerosis in venous grafts by reducing cholesterol uptake.

Animals↗

Vascugraft microporous polyesterurethane arterial prosthesis as a thoraco-abdominal bypass in dogs.

In their progression towards clinical acceptance, any new synthetic vascular grafts under development must undisputedly prove that the chemistry and structure used in the construction of the prostheses is safe and that their biocompatibility and performance as arterial substitutes are satisfactory without degradation or weakening of the device. This study was conducted to evaluate the safety of the microporous polyesterurethane Vascugraft by investigating its biocompatibility in terms of cellular proliferation, morphology and adhesion of human fibroblasts on virgin and blood-soaked Vascugraft prostheses, and its performance in vivo as a large calibre graft in a canine thoraco-abdominal bypass model for periods of implantation ranging from 4 h to 6 months. After 3 d incubation, better cell proliferation and adhesion were observed on blood-soaked Vascugraft than on a non-porous polyurethane graft, Mitrathane, and two other polytetrafluorethylene prostheses, Impra and Goretex. Furthermore, no leachable cytotoxic contaminants were released from the prostheses. In vivo, the Vascugraft has demonstrated a good performance with the development of an endothelialised internal capsule at both anastomoses 2 weeks after implantation, reaching the medial portion of the graft at 4 months. During this period, the prostacyclin I2/thromboxane A2 ratio increased and was higher than 1.0 at 2 months. In addition, the Vascugraft exhibited low surface thrombogenicity in terms of radiolabelled platelets and fibrin deposited. Chemically, as revealed by ESCA and FTIR analyses, a slight decrease in carbonate content was observed on the external surface of the Vascugraft during the early post-implantation periods. Breaks in the microfibrous structure were also observed at 4 and 6 months, occurring mainly in the anastomotic regions and believed to be stress-related. This study shows that the polymer used in the Vascugraft is biocompatible in terms of fibroblast proliferation and promotes fair healing characteristics. However, the chemical and structural surface modifications noted in this study are disturbing and question the total inocuity of the Vascugraft. Consequently, the decision by B. Braun Melsungen AG to end this project is both highly conscientious and professional.

Anastomosis, Surgical↗

Evaluating the Dialine vascular prosthesis knitted from an alternative source of polyester yarns.

The sudden and unilateral decision by E. I. DuPont de Nemours & Co., Inc., to withdraw its polymers for use in implantable devices has presented the medical device industry with an immediate and serious challenge to find alternative sources of biomaterials. In France, the company Cardial S.A. has already taken steps to find an alternative polyester yarn to replace Dacron by developing a new arterial prosthesis knitted from polyester yarns supplied by Rhône-Poulenc Fibres. This article describes an in vitro and in vivo study of this French device, called the Dialine prosthesis, with a view to determining its relative performance compared to current American and British prostheses, which rely on DuPont's Dacron yarn. In addition to analyses of the morphology and textile structure, and measurements of its physical and chemical properties, the Dialine graft was implanted as a thoracoabdominal bypass in dogs for periods ranging from 4 h to 6 months. In addition to our pathologic and histologic observations, we cleaned and evaluated the explanted prostheses for in vivo changes in dimensions, strength, and crystalline microstructure. The Dialine graft was found to differ structurally from other polyester prostheses because it is warp-knitted from a mixture of flat and texturized yarns with finer filaments. Its denser structure has a lower water permeability, greater flexibility and ease of handling, satisfactory strength, and dimensional stability, and it presents different textures on its luminal and external surfaces. The in vivo trial demonstrated that it has excellent biocompatibility and biostability over 6 months. With no thrombi observed on the luminal surface after 3 months, it has a faster rate of healing, generates compact external and internal capsules with a thinner neointima, and has an overall milder inflammatory response than is normally observed with Dacron-based prostheses.

Angiography↗

Polyvinylidene fluoride (PVDF) as a biomaterial: from polymeric raw material to monofilament vascular suture.

This study identified the effects of various manufacturing processes on the crystalline microstructure, mechanical properties, and biocompatibility of a polyvinylidene fluoride (PVDF) suture. To achieve this, changes in the crystalline microstructure and the tensile behavior of PVDF monofilaments were monitored in vitro after different thermal processing, coloration, and sterilization treatments. In addition, the in vivo biocompatibility of the manufactured and sterilized PVDF suture was assessed by using it to anastomose a preclotted polyester vascular prosthesis as a thoracoabdominal bypass in a series of dogs. The tissue response was followed by histologic and scanning electron microscopy over implantation periods ranging from 4 h to 6 months. Differential scanning calorimetry and infrared spectroscopy (FTIR-ATR) showed that thermal processing and the addition of a coloring agent had a direct effect on modifying the crystalline microstructure and hence changing the mechanical properties. For example, thermal processing converted some of the alpha phase into the beta and gamma polymorphs, whereas coloration led only to a major increase in the beta-to-alpha ratio. The tensile properties were found to be optimized when the relative proportion of the beta and gamma phases combined compared to the alpha form gave rise to an FTIR A509/A532 absorption ratio between 4.0 and 4.5. Sterilization was found to cause some modifications to the crystalline microstructure near the surface of the monofilaments, but it did not change their mechanical properties. Pathologic examination of the anastomotic regions after different periods of implantation revealed a minimal cellular response, with no mineralization, intimal hyperplasia, or excessive fibrous tissue reaction. This good biocompatibility, together with other desirable characteristics such as ease of manipulation and satisfactory mechanical strength, makes PVDF an attractive alternative monofilament suture material for cardiovascular surgery.

Animals↗

Carbodiimide cross-linked gelatin: a new coating for porous polyester arterial prostheses.

The performance of a polyester arterial prosthesis impregnated with gelatin and cross-linked with carbodiimide (Uni-graft) was compared with its porous parent graft (Protegraft) using a canine thoraco-abdominal bypass model. The grafts were investigated in terms of their handling characteristics, imperviousness at implantation, surface thrombogenicity and healing behaviour. Prostheses 30 cm in length were implanted for the following periods: 4, 24 and 48 h, 1, 2 and 4 weeks, 2, 3, 4, 5 and 6 months. Both types of graft had good handling characteristics. The ready-to-use impregnated graft provided satisfactory haemostasis at implantation with no blood permeating through the wall after flow was restored. Both grafts exhibited low surface thrombogenicity, as determined by the uptake of labelled fibrin and platelets, and the healing sequence of the impregnated graft after resorption of the gelatin was equivalent to that of the preclotted control. Biodegradation of the gelatin was complete within 1 month of implantation with the subsequent development of a collagenous internal capsule at both anastomoses. Endothelial cells were observed between 4 and 6 months, but were confined to small islets distributed along the luminal surface. The prostacyclin/thromboxane A2 (PGI2/TXA2) ratio, which gives an indication of the level of endothelial cell activity, was greater than 1.0 after 1 week of implantation for the control graft. For the impregnated graft it reached 1.0 only after 3 months of implantation, but remained above 1.0 for periods of up to 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Removing fresh tissue from explanted polyurethane prostheses: which approach facilitates physico-chemical analysis?

Chemical, physical and structural analyses of polymers from explanted vascular prostheses are frequently jeopardized because of incomplete removal of the encroaching host tissue. In this study, microporous polyurethane arterial prostheses implanted as a canine thoraco-abdominal bypass were explanted after 1 and 12 months and were cleaned without fixation using four different digesting enzyme treatments, including collagenase, pancreatin and trypsin alone and collagenase and pancreatin in series, followed by washing in a solution of Triton X-100 detergent. By following this approach all the fresh tissue attached to the external and internal walls of the prostheses was removed with minimal damage to the underlying synthetic polymer. The morphology of the explanted and cleaned polyurethane prostheses could be obtained readily by light and scanning electron microscopy. Surface microporous features and the presence of polyurethane microfibres that had experienced in vivo biodegradation could therefore be identified easily. The surface and bulk physico-chemical properties of the polyurethane polymer were determined by electron spectroscopy for chemical analysis, attenuated total reflectance-Fourier transform infrared spectroscopy and differential scanning calorimetry. It was found that the most successful approach for removing fresh tissue and exposing a clean and uncontaminated polyurethane surface was to incubate the explanted samples first in collagenase followed by digestion in pancreatin. This particular cleaning technique has proved valuable in enabling us to monitor small in vivo changes in the surface chemistry and in the bulk microphase segmented structure of polyurethane biomaterials.

Animals↗

Fresh venous allografts in peripheral arterial reconstruction in dogs. Effects of histocompatibility and of short-term immunosuppression with cyclosporine A and mycophenolate mofetil.

To date, no arterial substitute has been shown to be as effective as the autologous saphenous vein in peripheral revascularization procedures. In the present study, the venous allograft was evaluated as a vascular substitute in terms of patency and induction of host immune reactivity, whether used in major histocompatibility complex-incompatible, major histocompatibility complex-incompatible dogs. The immunosuppressive drug therapies were given for a period of 31 days, beginning 1 day before transplantation, and consisted of the use of cyclosporine A, mycophenolate mofetil, or a combination of both. All histoincompatible allografts were thrombosed at 4 or 8 weeks after transplantation with antibody development and cell-mediated cytotoxicity in the graft, whereas histocompatible allografts showed late stenosis without immunologic reactions directed toward donor cells. Given alone, neither cyclosporine A nor mycophenolate mofetil improved the overall patency of venous allografts; thrombosis occurred shortly after cessation of immunosuppression. Still, the cyclosporine A-mycophenolate mofetil combination therapy led to a 100% patency rate at 20 weeks after implantation and immune reactions were markedly reduced. This study shows that the fresh vein allograft is still an attractive and functional alternative to the autologous saphenous vein if the host immunologic reactions are controlled by cyclosporine A-mycophenolate mofetil immunosuppression.

Animals↗

Luminal surface concentration of lipoprotein (LDL) and its effect on the wall uptake of cholesterol by canine carotid arteries.

PURPOSE: The effect of near-wall blood flow velocity and plasma filtration velocity across the arterial wall on luminal surface concentration of low-density lipoproteins (LDL) and the uptake of tritium-cholesterol were investigated. METHODS: A numeric analysis of LDL transport in steady flow, over the range of physiologically relevant flow rates, predicted a surface concentration of LDL of 4% to 16% greater than that in the bulk flow. The LDL surface concentration increased linearly with filtration velocity and inversely with wall shear rate. RESULTS: These were validated experimentally in canine carotid arteries. When the transmural pressure was increased from 100 to 200 mm Hg, the filtration velocity increased from 5.13 x 10(-6) cm/sec to 8.41 x 10(-6) cm/sec, whereas the normalized uptake rate of tritium-cholesterol increased from 3.58 x 10(-4) cm/hour to 7.36 x 10(-4) cm/hour. CONCLUSION: These results indicate that lipids accumulate at the luminal surface in areas where blood flow velocity and wall shear stress are low and where the permeability of the endothelial layer is enhanced. Moreover, the rate of lipid infiltration into the blood vessel walls is affected by the luminal surface concentration. These findings are consistent with chronic hypertension and elevated blood cholesterol concentrations being major risk factors for atherosclerosis.

Animals↗