Biomedical subjects

R Tu

Publications and source records attributed to R Tu.

At least 37 records · Page 2Linked to original sources

PubMed1993

Hemodynamic evaluation of a bioprosthetic venous prosthesis.

PURPOSE: A prosthetic venous valve must be biocompatible and nonthrombogenic and function in the venous circulation. Biocompatibility and thrombogenicity of our prosthesis have been examined in prior animal experiments, and 91% of valve conduits including early prototypes are patent at 3 weeks. However, evaluation of valve function is much more difficult in animals; therefore in this study the function of excised valves was evaluated ex vivo. METHODS: Nine bovine jugular vein conduits, each with one bileaflet venous valve, were harvested and placed in a venous flow simulator. Flows and pressures were adjusted to mimic human respiratory and hydrostatic variations. Each valve and conduit was tested for variations in valve diameter and sinus expansion in response to flow. Valve opening and closing times and valve competence were measured in response to pressure changes. After testing, each specimen was glutaraldehyde fixed and assessed a second time. RESULTS: Valve orifice area increased in response to flow in both fresh and fixed tissues. Maximum valve orifice area was reduced by fixation (27.7%) at full flows (p < 0.05). Valve sinus dimensions increased in response to increased pressure until maximum expansion was achieved (33 mm Hg). This was reduced 15.3% in fixed tissue (p < 0.05). Valve opening times (at < 1 mm Hg gradient) were slightly longer in fixed compared with fresh tissue (0.43 +/- 0.09 vs 0.41 +/- 0.13 second; p < 0.05). Valve closing times were comparable in both states (0.43 +/- 0.08 vs 0.49 +/- 0.07 second). Three fresh and seven fixed specimens that were subjected to 287 mm Hg back pressure exhibited minimal reflux. CONCLUSIONS: Size and availability make the bovine jugular vein valve an ideal venous valve substitute. Glutaraldehyde fixation renders the tissue biocompatible and nonthrombogenic while preserving anatomic integrity and leaflet strength and flexibility. Mounted and stented in a sewing sleeve, this prosthesis could represent the first generally applicable clinical solution to chronic venous insufficiency and venous hypertension.

Adult↗

PubMed1993

Analysis of the neutralizing antibody response to the measles virus using synthetic peptides of the haemagglutinin protein.

Infection or immunization with measles virus induces a protective immune reaction including neutralizing antibodies against the haemagglutinin and fusion protein. The reactivity of the polyclonal IgG response of sera obtained from late convalescent donors was studied, using overlapping 15mer peptides covering the complete sequence of the measles virus haemagglutinin. Most sera reacted with a similar set of peptides generating a characteristic binding pattern. The reactive peptides correspond to a region mediating cell hemolysis (aa310-325), to regions which serve as targets to neutralizing antibodies and to a putative transmembrane region (aa35-58). The latter region contains also a human T-cell epitope providing evidence of a non-random association of T- and B-cell epitopes. We also immunized different strains of mice and rabbits with measles virus. In contrast to the human sera, animal sera with strong neutralizing activities did not react with any of the H-protein peptides. The mostly weak reactivities with the linear sequences contrast with the strong neutralizing activities of the human or animal antibodies, suggesting that these primarily recognize the fusion protein or conformational epitopes of the haemagglutinin protein.

Adult↗

PubMed1993

A compliant biological vascular prosthesis.

One requirement of the mechanical parameters for an acceptable vascular prosthesis is compliance. The compliance of a vascular prosthesis is defined as the fractional change in luminal volume per unit change in applied pressure. A compliant prosthesis has been correlated to prosthesis patency and long-term efficacy in an animal study. However, there have been very few reports on how to manufacture a compliant prosthesis. It is the objective of this study to research the processing methods to manufacture a reasonably compliant vascular prosthesis. A new fixative, polyepoxy compound, was used to fix an artery. The arteries were fixed under different degrees of longitudinal retraction. By locking in the collagen micro-structure at an overly relaxed state and then crosslinking said collagen, the resulting biological prosthesis exhibited extreme compliance and pliability. A prosthesis matching its arterial origin in tensile modulus was achieved by crosslinking an artery at its 45% retraction longitudinally. This flexible prosthesis showed a volumetric compliance index of 18.4 +/- 0.9 % delta/100 mmHg and a longitudinal tensile modulus of 942 grams/cm2. Our current study indicated that a prosthesis fixed with polyepoxy compounds has shown more pliability than that with glutaraldehyde. Further animal study to correlate prostheses patency to different degrees of compliance is needed to confirm this proposed manufacturing approach.

Bioprosthesis↗

PubMed1993

Development and evaluation of a pliable biological valved conduit. Part I: Preparation, biochemical properties, and histological findings.

Different types of external valved conduits have been used for the repair of complex congenital cardiac anomalies that may have otherwise been inoperable. However, an ideal conduit has yet to be found due to complications such as stenosis, thrombosis, calcification of the valve and graft wall, and "peeling" of the neointima. To address those problems, a new extracardiac valved conduit made of bovine jugular vein was developed and evaluated in a preliminary animal study. Harvested bovine vein containing a naturally existing valve was initially incorporated with protamine on the inner surface and then was cross-linked in diglycidyl ether (DE). Fixation with DE allowed the vein and its leaflets to retain a tissue-like elasticity. To provide antithrombogenicity to the graft, heparin was introduced into the lumen to bind ionically to the pre-entrapped protamine. The biological valved conduit of approximately 14 mm diameter was implanted from the right ventricle to pulmonary artery as bypass graft in three dogs. After implantation, the native main pulmonary artery was ligated between the anastomotic sites of the bypass conduit. No anticoagulant or antiplatelet drugs were administered after surgery. One DE-fixed valved conduit was retrieved at 3 months, and the others were removed at 5 months. Only small thrombus areas were found on the white luminal surfaces. The valves and the conduits maintained softness and pliability, similar to before implantation. Additionally, the collagen content, shrink temperature, and tanning index of this newly developed biological valved conduit before and after fixation were measured in the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Development and evaluation of a pliable biological valved conduit. Part II: Functional and hemodynamic evaluation.

Many congenital cardiac malformations may require a valved conduit for the reconstruction of the right ventricular outflow tract. In spite of many endeavors made in the last 25 years, the clinical results of right ventricular outflow tract reconstruction with currently available valved conduits are still not satisfactory. Specific problems encountered clinically include suboptimal hemodynamic performance, conduit kinking or compression, and fibrous peeling from the luminal surface. To address these deficiencies, we undertook the development of a biological valved conduit: a bovine external jugular vein graft with a retained native valve cross-linked with a diglycidyl ether (DE). This study, using a canine model, was to evaluate the functional and hemodynamic performance of this newly developed valved conduit. Three 14 mm conduits, implanted as bypass grafts, right ventricle to pulmonary artery, were evaluated. The evaluation was conducted with a noninvasive color Doppler flow mapping system at pre-implantation, immediately post implantation, one- and three-months post implantation, and prior to retrieval (five-months post implantation). The two-dimensional tomographic inspection of the leaflet motion at various periods post implantation showed that the valvular leaflets in the DE treated conduit was quite pliable. No cardiac failure or valvular dysfunction was observed in any of the studied cases. The color Doppler flow mapping study demonstrated that the valve in the DE treated conduit was competent, with no conduit kinking or compression observed in any of the three cases. The spectral Doppler velocity study evidenced that the transvalvular pressure gradients of the DE treated conduit were minimal as compared to those of the currently available conduits. In conclusion, from the functional and hemodynamic performance points of view, this newly developed valved conduit is superior to those currently available.

Animals↗

PubMed1993

Heparinization of biological vascular graft reduces fibrin deposition.

An alternative graft is needed for coronary bypass operations in patients lacking suitable autologous vessels. We therefore studied Denaflex, a biologic graft, in a dog ex-vivo shunt model to determine whether heparin treatment makes this graft less thrombogenic. Comparison was also made to Bioflow, a nonheparinized biologic graft. Fibrinogen deposition during high flow (593 +/- 202 ml/min) decreased from 672 +/- 467 ng/mm2 in nonheparinized Denaflex grafts to 448 +/- 298 ng/mm2 (p < 0.05) in heparinized Denaflex grafts. At low flow (117 +/- 13 ml/min), heparinization of Denaflex grafts similarly decreased fibrinogen deposition from 1102 +/- 601 ng/mm2 to 703 +/- 405 ng/mm2 (p < 0.05). At both flow rates fibrinogen deposition in Bioflow grafts was less than in nonheparinized Denaflex, but was similar to heparinized Denaflex grafts. Platelet deposition was not influenced by heparinization of Denaflex grafts and was similar among Denaflex and Bioflow preparations. Whether Denaflex performs acceptably in vivo as a xenograft requires extensive study.

Animals↗

PubMed1993

Evaluation of collagen modification and surface properties of a bovine artery via polyepoxy compound fixation.

Collagen of bovine internal thoracic artery (BITA) was treated with glutaraldehyde (GA) or polyepoxy compounds (PC). This study was to evaluate the surface properties as a result of tissue tanning reaction with PC. The fixation resulted in a significant reduction of available lysine, histidine, and other amino acid residues in PC fixed grafts as compared to fresh pre-fixed arteries. Among them, the lysine (Lys) content was reduced by about 80%, indicating that PC reactions mainly involve with Lys residues. Both PC and GA treatment led to crosslinking as evidenced by the increase in the denaturation temperature. The critical surface tension and the Fourier Transform Infrared Spectrum (FTIR) on a pre-implant and its 96 days explant were evaluated and found to be similar. The FTIR analysis of a pre-implant and the 96 day explant indicated that there was no lipid deposition.

Amino Acids↗

PubMed1993

A preliminary study of the fixation mechanism of collagen reaction with a polyepoxy fixative.

A new biomaterial has been developed by fixing native collagens with a polyepoxy compound (PC) fixative. Prior studies have shown that this biomaterial has comparable properties as compared to collagen fixed with glutaraldehyde (GA) and thus has a great promise for use as an implantable bioprosthesis. The purpose of this study was to understand the mechanism of the amino acids-PC reactions in the fixation process. Bovine arteries were fixed with PC under various pH, concentration and temperature conditions as a function of fixation time. Individual amino acid components in the fresh and the fixed arteries were assayed using a Beckman amino acid analyzer to determine the degree of tanning. The denaturation temperature (Td) was also measured on each sample. Since the denaturation temperature is a direct indication of cross-linking of individual amino acids with the fixative, the difference in the degree of tanning for the same increase in Td may be indicative of the quantity of the masked, non-cross-linked amino acids. The fixation reaction data indicated that not all amino acids were cross-linked upon contacting the PC fixative. Masking appeared to be more substantial with a fixation at higher pH values.

Amino Acids↗

PubMed1992

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.

Animals↗

PubMed1992

Noninvasive color Doppler inspection of small-diameter vascular grafts implanted in canine carotid and femoral arteries.

To noninvasively evaluate a small-diameter vascular graft (approx. 4 mm in diameter) developed for coronary artery bypass application, a state-of-the-art color Doppler flow mapping system was applied to inspect various grafts implanted in 5 canines. The grafts, including Denaflex, Gore-Tex ePTFE, and Bioflow, were implanted interpositionally in the carotid and femoral arteries. Inspections were conducted with a 5 MHz linear vascular transducer at 6 weeks postimplantation and 12 weeks postimplantation, immediately prior to retrieval. In the carotid artery position, all 5 Denaflex grafts were patent throughout the implantation period while 2 of the 5 Gore-Tex grafts were occluded at 6 weeks, and 1 more was occluded at 12 weeks. In the femoral artery position, all 5 Denaflex grafts were patent at 6 weeks; however 2 were occluded at 12 weeks. For the Bioflow grafts at 6 weeks, 3 were patent, and 2 were occluded. The same results were observed at 12 weeks. The color Doppler inspection results indicated a higher patency rate in the carotid artery position than in the femoral artery position. Furthermore, the volumetric flow rate and the wall shear stress measured with the pulsed Doppler in the carotid artery were greater than in the femoral artery. These findings suggest that the hemodynamic "environment" in which the graft was implanted may affect the graft patency rate. The Doppler inspection results obtained at 12 weeks, identical with those observed after retrieval, demonstrated that color Doppler flow mapping is a reliable method to noninvasively inspect blood flow through small-diameter vascular grafts.

Animals↗

PubMed1992

Evaluation of two epoxy ether compounds for biocompatible potential.

Bovine arterial tissue exposed to two epoxy ether compounds (Denacol EX-313 and Denacol EX-810) was evaluated for its biocompatible potential by in vitro and in vivo test procedures. The battery of test procedures included percent Inhibition of Cell Growth, Medium Eluate Method (MEM), Agar Overlay (AO), Blood Compatibility, Acute Mouse Systemic Injection, Rabbit Intracutaneous Irritation, Rabbit Subcutaneous Implantation, Guinea Pig Maximization, and Ames Tests. The epoxy exposed tissue was found to be noncytotoxic, nonmutagenic, and biocompatible by the test methods employed. In addition, the maximum concentrations of the unreacted Denacol EX-313 and EX-810 solutions found to demonstrate noncytotoxic reactions by the MEM and AO procedures were identified as 55 and 60 ppm for the MEM and 150 and 200 ppm for the AO procedure, respectively. These studies suggest that Denacol EX-313 and EX-810 are acceptable solutions for the processing of implantable tissue provided the epoxy residuals remain below those levels found to be cytotoxic.

Animals↗

PubMedDate not supplied

Graft compliance and anastomotic flow patterns.

The oscillatory flow patterns at the venous anastomosis of a hemodialysis angioaccess loop graft system were studied using two new compliant vascular prostheses: a longitudinally compliant polytetrafluoroethylene-composite (Baxter Ultraflex PTFE-Plus) graft (BA) and a radially compliant ultrafine polyester fiber (TORAY-UFPF) graft (TR). A non-compliant Gore-Tex polytetrafluoroethylene graft was used as the control. The experimental grafts were 8 mm inside diameter x 25 cm long. Flow experiments were done in a transparent, elastic bench-top flow model; fabrication was based on silicone rubber casts obtained from femoral-to-femoral arteriovenous loop grafts surgically implanted in dogs. The loop graft constructed in the dog model was made to mimic the branchial-to-cephalic angioaccess loop graft commonly used in hemodialysis patients. The flow model was connected to a pulse generator, an adjustable arterial afterload, and a venous afterload. Under identical input conditions, the pressure and flow waveforms were monitored simultaneously at the proximal and distal ends of both the arterial and venous anastomoses. For each graft studied, the anastomotic flow field was visualized using laser illuminated hydrogen bubbles as tracers. At pulse rates of 60 and 90 beats/min, graft flow rates were 2.2 and 2.5 L/min, respectively. Among the grafts studied, measurable differences in pressure and flow wave attenuation and their respective phase lags resulted in characteristically dissimilar flow patterns at the venous anastomosis. Growth of the separation zone at the toe of the anastomosis, and the pattern of retrograde flow in the distal vein are visibly different in all three grafts.

Animals↗

PubMedDate not supplied

In vitro performance of venous valve prostheses. An experimental model study.

The performance of fresh and glutaraldehyde fixed bovine jugular vein valves (10 mm diameter) was investigated in an experimental flow loop that provides adjustable flow rates and a downstream oscillatory pressure. Three different venous valve (VV) conduit geometries (curved [C], straight [S], and tapered [T]), were tested. The flow loop consisted of two independently adjustable components, with the mean flow generated by adjusting the elevation difference between the head tank and outflow chamber. An adjustable sinusoidal pressure pulse was superimposed on the downstream of a VV to mimic the respiratory effects. Flow visualizations were made using 100 microns mica chip tracers in the laser illuminated flow fields. To assess VV performance under various flow conditions, the closure opening (CO), partial opening (PO), and leaflet fluttering (LF) were evaluated. At a given pulse pressure, the three conduits required different flow rates to reach CO mode. At 12 cm H2O pulse pressure, the fresh valve in C-conduit exhibited stable CO operation at a flow rate of 1.01 ml/sec. That in S and T conduits required 1.67 ml/sec and 2.25 ml/sec, respectively. At higher flow rates, PO and LF performances were observed in all three conduits. Different threshold values of pulse pressure were needed to reestablish the CO operation mode for the C, S, and T conduits, individually. These observations provide some insight into the role of conduit geometry and sinus configuration in the function of VV.

Animals↗

PubMedDate not supplied

Sterilization of a small caliber vascular graft with a polyexpoxy compound.

Sterilization of tissue based medical devices via cold sterilization processes has been limited to formaldehyde, glutaraldehyde, and mixtures of the same with alcohols and surfactants. The authors report the sterilization of a small caliber vascular graft with a combination of diglycidyl ether and ethanol. The sterilant contains 1-4% diglycidyl ether and 10-20% ethanol as an aqueous solution. Sterilization is achieved after exposure of the graft to the sterilant solution for a period of 7 days at an elevated temperature (30 degrees - 40 degrees C). The biologic indicator selected for efficacy studies was Bacillus subtilis niger ATCC 9372 (endospores). The grafts were inoculated with a concentrated endospore suspension and immersed in the sterilant solution for increasing time periods. After extensive rinsing over membrane filters to remove any residual sterilant, the grafts and filters were cultured in tryptic soy broth. D10 values were calculated using a fraction-negative, most probable number technique. Additionally, many representative bacteria and fungi were tested and found to be susceptible to the new sterilant developed. The diglycidyl ether/alcohol sterilant developed was found to be efficacious for sterilization of the tissue based vascular grafts tested.

Bacteria↗

PubMedDate not supplied

Dynamic internal compliance of a vascular prosthesis.

A new technique was used to measure dynamic internal compliance of a blood vessel or vascular graft subjected to dynamic internal pressure. The internal compliance can be broken into three categories: the volumetric compliance (CV), defined as (dV/V)/dP; the longitudinal compliance (CL), defined as (dL/L)/dP; and radial compliance (CR), defined as (dR/R)/dP. It can be shown mathematically that CV = 2 CR + CL. Thus, measuring any two of the three entities will also give the value for the third. A Dynatek DCT1 dynamic compliance tester was used for measuring the compliance of DenaflexTM biologic grafts and fresh bovine internal thoracic arteries, from which the Denaflex grafts were obtained by fixation. Volumetric compliance was obtained with the test sample mounted in a loose loop that allowed the sample to move both radially and longitudinally. By mounting the sample in a straight fashion that limited longitudinal movement, the radial compliance was determined. The longitudinal compliance was then calculated from the above relationship. Test results show that the fresh bovine artery had an average volumetric compliance of 26.1%/100 mmHg, radial compliance of 9.5%/100 mmHg, and longitudinal compliance of 7.2%/100 mmHg. The Denaflex vascular graft showed a reduction in longitudinal and radial compliance, compared to the fresh raw artery, as a result of extensive fixation.

Animals↗

PubMedDate not supplied

Performance of a longitudinally compliant PTFE vascular prosthesis in an ovine A-V fistula model.

Nine chronic implants of 6 mm diameter vascular grafts were performed in an ovine model to compare the performance of the longitudinally compliant Ultraflex PTFE-Plus vascular prosthesis with that of the Gore-Tex reinforced expanded polytetra fluoroethylene (PTFE) graft. Implants were performed in the sheep neck as right carotid to left jugular arterio-venous (A-V) grafts. Grafts were explanted after 6 months unless they occluded earlier. The Ultraflex graft demonstrated superior handling characteristics during implant. Patency rate at 6 months was 60% (three of five) for the Ultraflex graft (experimental graft by Baxter Edwards, CVS Division, Irvine, CA), and 25% (one of four) for the Gore-Tex graft (WL Gore & Associates, Inc., Flagstaff, AZ). The Gore-Tex prosthesis had more calcification of the graft wall.

Animals↗

PubMedDate not supplied

Dynamic internal compliance measurements of fresh and fixed artery.

A new device is used to compare dynamic internal compliance of biologic vascular prostheses derived from bovine artery. These grafts were prepared using dialdehyde starch (DS), and a polyepoxy polyether compound (PC), as crosslinking agents. Internal compliance was measured using the Dynatek DCT1 Dynamic Compliance Tester, developed by Dynatek Laboratories. This device utilizes a variable speed DC motor coupled to miniature bellows, which displace a stroke volume controllable to within 0.5 microliter. The bellows displace fluid into and out of the graft, resulting in a sinusoidal change in internal pressure. Volumetric displacement is monitored by a linear voltage displacement transducer (LVDT) mounted on the motor coupling, whereas internal graft pressure is monitored by a miniature pressure transducer mounted on the closed end of the graft. For this series of experiments, a pressure range of 80-120 mmHg was used, with a cycle speed of 80 cycles/min. Preliminary results indicate that PC fixation of bovine artery results in a vascular graft with internal compliance somewhere between fresh tissue and DS fixation. This data confirms qualitative assessment. The DCT1 provides valuable comparative information on the dynamic internal compliance of vascular prostheses. These measurements reflect what occurs in the graft lumen, since they take into account wall compression and axial deformation. Further development is required to separate radial and longitudinal compliance components.

Animals↗

PubMedDate not supplied

Evaluation of compliant and noncompliant PTFE vascular prostheses.

Four chronic implants of 6 mm diameter grafts compare a new longitudinally compliant PTFE-composite vascular prosthesis (ULTRAFLEX PTFE-PLUS) with clinical grade microporous expanded polytetrafluoroethylene (PTFE). Implants were carried out in the ovine carotid-jugular position as A-V fistulae. All four grafts were subjected to sham dialysis punctures in identical fashion with 14-gauge needles. After 60 days the grafts were explanted and submitted for histologic evaluation. All four grafts were patent at explant. The compliant PTFE (ULTRAFLX PTFE-PLUS) lumen surface was thrombus free. Neointima lining at the proximal and distal anastomoses was similar in both test and controls. Tissue ingrowth and outer capsule formation were virtually identical. Foreign body reaction was minimal. Superior handling and self-sealing properties distinguished test from controls. Long term animal studies are in progress for vascular access and peripheral applications.

Animals↗