PubMed HealthSearch

Biomedical subjects

R C Eberhart

Publications and source records attributed to R C Eberhart.

At least 19 recordsLinked to original sources

Alkylation of cellulosic membranes results in reduced complement activation.

4-Vinyl pyridine was grafted to the surface of the cellulosic membrane Cuprophan, and subsequently alkylated with both C10 and C16 aliphatic chains. Complement activation of heparinized human blood, corrected for anaphylatoxin adhesion, was measured by radioimmunoassay. The surface treatments both yielded substantial reductions in C5a activity, with a lessor reduction in C3a and C4a activity. Alkylation with 10 and 16 carbon chains resulted both in enhancements of albumin adsorption and stability. These enhancements as well as the reductions in complement activation were statistically indistinguishable between the two treatments. The reduction in complement activation was influenced more by adsorption of endogenous albumin and possibly by the vinyl pyridine graft, than the removal of surface active hydroxyl groups from Cuprophan.

Adsorption

Endothelial cells on Dacron vascular prostheses: adherence, growth, and susceptibility to neutrophils.

Human umbilical vein endothelial cells (HUVEC) on knitted and woven Dacron prostheses were compared with HUVEC on smooth surfaces (tissue culture polystyrene, PET film, and Natrix) with regard to adherence, growth, and susceptibility to injury by neutrophils (PMN). These are properties of importance for successful seeding or coating of prostheses. For prosthetic material of given macroscopic dimensions, more endothelial cells (EC) adhered than to smooth surfaces. However, the prostheses had a greater effective surface area as determined by the number of EC at confluency. When this parameter was taken into account, fewer EC were found adherent to prosthetic material per unit effective surface area than for the smooth surface substrates. Growth on prostheses was clearly inferior to that on smooth surfaces, and EC on prostheses were more susceptible to attack by activated PMN than on smooth surfaces. These differences may reflect the topographic differences in cells attached to fibers where they assume more distorted shapes by stretching to span fibers.

Antibodies, Monoclonal

Neonatal extracorporeal membrane oxygenation complicated by sepsis. Extracorporeal Life Support Organization.

The onset of sepsis in neonates while on extracorporeal membrane oxygenation (ECMO) may portend adverse results. Nevertheless, ECMO has been used as a therapy in the management of septic conditions. This study assessed morbidity and mortality in neonates in whom septic complications developed while they were on ECMO. Of 5,123 neonates in the Extracorporeal Life Support Organization Registry undergoing ECMO for nonseptic indications, 217 patients had development of septic complications. A multivariate logistic regression analysis that considered 15 pre-ECMO criteria was performed to evaluate outcome. Mortality was higher in the septic group (35% versus 17%; p < 0.002) and ECMO duration averaged 85 hours longer (p < 0.001). Septic neonates had a greater frequency of complications including seizures, gastrointestinal bleeding, renal dysfunction, and metabolic problems (all p < 0.05). Transfusion requirements were doubled. Oxygenator thrombi and hemofilter malfunction occurred more often in septic patients (p < 0.03). New strategies to prevent sepsis and associated thrombotic and metabolic complications may be indicated. A critical reappraisal of continued aggressive support may be warranted when septic complications develop in neonates during ECMO.

Analysis of Variance

Comparison of tissue factor and prostacyclin production by human umbilical vein endothelial cells on Dacron vascular prostheses and Dacron smooth films.

The functional capacity of human umbilical vein endothelial cells (HUVEC) grown on Dacron (polyethylene terephthalate; PET) vascular prosthetic material was compared with the function of cells on smooth surfaced PET, tissue culture polystyrene (TCPS), and Natrix-coated TCPS. Prosthetic materials include two knitted fabrics (Bionit I and II) and two woven preparations (DeBakey Soft Woven and Extra Low Porosity). Two entities produced by HUVEC that influence blood coagulation were assessed: the procoagulant tissue factor (TF) and the anticoagulant prostacyclin (PGI2). Although TF activity was stimulated on all substrates by endotoxin (LPS), there was no difference among prostheses and no difference among smooth surface materials, but TF was reduced in cells on the prosthetic materials relative to those on smooth surface substrates. The reduced TF production by HUVEC on prosthetic material could be reversed by returning them to TCPS. In contrast, PGI2 production on prostheses was comparable to that on smooth surfaces for both stimulated and unstimulated cells. Stimulation with histamine (1 microM) gave a 2.4-fold increase in PGI2 whereas mellitin (10 micrograms/ml) increased production 12.5-fold. The differential response of HUVEC with regard to these two coagulation factors, one of which is secreted and the other membrane bound, may reflect the distorted shape of cells on fibers of the prosthesis.

Biocompatible Materials

Anatomic basis for mitral valve modelling.

The increasing popularity of mitral valve repair and current interest in replacement with a mitral homograft or heterograft warrant a new look at the normal functional anatomy of the system. We conducted a detailed review of the anatomic structure of both the intact and excised mitral apparatus of porcine and human species. The following intact structural dimensions were measured: total annular length, anterior and posterior annular length. Excised measurements included: total annular length, anterior and posterior annular lengths, leaflet edge lengths, leaflet heights, and anterolateral and posteromedial commissural heights. Leaflet area was calculated from planimetric measurements. Chordal lengths were measured and distribution recorded. The majority of leaflet measurements were not statistically different between groups. For both groups, the measured annular length increased significantly upon valve excision. In both groups, the posterior leaflet area was significantly larger than the anterior leaflet area, and the area of each leaflet alone was significantly greater than the calculated orifice area. Chordal length was not significantly different between groups, however, distribution varied slightly with the ratio of origins to insertions being 8:1 (porcine) and 5:1 (human). The results are consistent with previous studies of the human mitral valve. This study showed little difference between human and porcine data, and the porcine valve was identified as an appropriate model for further investigation of the mitral valve system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Molecular surface tailoring of biomaterials via pulsed RF plasma discharges.

A pulsed RF plasma glow discharge is employed to demonstrate molecular level controllability of surface film deposits. Molecular composition of plasma deposited films is shown to vary in a significant manner with the RF duty cycle. Three fluorocarbon monomers are used to illustrate the process. All three exhibit a trend towards increased surface CF2 content with decreasing pulsed RF duty cycle, including exclusion of oxygen. Significant variations in carbon-fluorine surface functionalities are obtained over a controllable range of film thickness. Film growth rate measurements reveal the occurrence of surface reactions during significant portions of the off portion of the duty cycle. Albumin adsorption on fluorocarbon-treated PET films is unchanged from PET controls for a 100-fold range of bulk concentrations and 60-fold range of adsorption times. However, increased retention of albumin is observed following incubation with protein-denaturing sodium dodecyl sulfate solution, the retention decreasing with increasing bulk concentration of albumin. The increased retention of albumin suggests the treated surfaces may have promise as biocompatible materials.

Adsorption

Differential collagen distribution in the mitral valve and its influence on biomechanical behaviour.

Surgical repair of the mitral valve primarily involves endogenous valve tissue, however, the intrinsic mechanical behaviour of the tissue is not well described. To address this issue, porcine mitral valve leaflets were examined histologically and engineering concepts were applied to understand the mechanical behaviour of the layered tissue. Rectangular portions were excised from the anterior and posterior leaflets, either parallel or perpendicular to the annulus, and sections were stained for collagen (Masson's trichrome). The cross sectional layers of the valve (atrialis/spongiosa, fibrosa, and ventricularis) were identified by differences in cellularity and collagen density. The fibrosa is composed of dense collagen, while the atrialis/spongiosa and ventricularis are composed of loose collagen. Layer thicknesses were recorded digitally across the section. These values were averaged within tissue groups to determine changes in layer thickness over the length of the sample and average thickness of each layer. In all tissue groups, the fibrosa was the thickest layer, and the atrialis/spongiosa layer was thicker than the ventricularis layer. The total and fibrosa layer thicknesses of the anterior leaflet were significantly thicker than in the posterior leaflet. Mechanical engineering analysis of the layered structures under tension indicated that the anterior leaflet would be able to support greater tensile loads than the posterior leaflet. The layered arrangement was then examined as a beam in bending, and was shown to decrease the resistance of leaflets to bending, and decrease the overall bending stresses on the leaflet. This type of analysis may be extrapolated to gain insight into changes in function in diseased valves as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Continuous thermodilution cardiac output measurement in sheep.

A technique has been developed to continuously measure cardiac output by means of the principles of thermodilution. Pulmonary artery catheters were modified by placing a 10 cm filament near the usual injectate port. Small amounts of heat were infused according to a randomly repeating binary on-off sequence. The distal blood temperature was recorded and cross-correlated with the heat waveform to produce a dilution curve and calculate cardiac output. The technique was compared with bolus thermodilution in seven sheep. Cardiac output ranged from 1.5 to 13.2 L/min, and heart rate varied from 59 to 180 beats/min. The linear regression between the data obtained by the two methods is represented by the equation y = 1.00x + 0.13; the correlation coefficient, R, is 0.97, and the p value is less than 0.0001.

Animals

T lymphocyte modification with the UTA microporous polyurethane vascular prosthesis: in vivo studies in rats.

Sequential quantification of blood T cell subsets by immunocytofluorometry was used to investigate the immune response of microporous polyurethane vascular prostheses after intraperitoneal implantation in rats. The experimental prosthesis, as developed by the University of Texas-Arlington group (UTA), and the Mitrathane prosthesis, as developed by Matrix Med., were implanted for 1, 2 and 6 weeks and compared with ePTFE and wounded rats without prostheses (control group). The implants were examined for histopathology by light microscopy. The percentages of CD4-(helper) and CD8-(suppressor) bearing cells of the PTFE group were significantly lower (p less than 0.05) than the control group 1 week post-implantation. The UTA and the Mitrathane grafts exhibited a significant decrease in both T cell subsets at 1 week, and CD4-bearing cells at 2 weeks. At 6 weeks, T cell subsets were similar among all groups. The ratio of CD4/CD8- cells was similar among all groups except for the PTFE group, which was lower than the control group after 1 week. Histological examination of Mitrathane and UTA grafts showed an acute phase of inflammation which lasted at least 2 weeks. Some foreign body giant cells (FBGC) were present 2 weeks post-implantation, and encapsulation was greater than that observed with PTFE grafts. On the other hand, PTFE grafts exhibited a different pattern of inflammation compared to polyurethane grafts. PTFE implants exhibited a moderate chronic inflammatory response for the first week, as shown by the formation of FBGC. At 2 and 6 weeks, the grafts were encapsulated by a thin layer of collagenous tissue and FBGC were still present around the implants, mostly located in contact with the reinforcing mesh.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Aortic valve morphology influences regurgitant volume in aortic regurgitation: in vitro evaluation.

STUDY OBJECTIVE: According to the Gorlin hydraulic orifice equation, aortic regurgitation volume can be determined by the regurgitant orifice cross sectional area, diastolic filling period, mean pressure gradient between the aorta and left ventricle, and a constant relating the coefficients of contraction (Cc) and velocity (Cv). This study was performed to determine whether variation in aortic valve morphology affects regurgitant flow volume, Cc and Cv. DESIGN: Four aortic valve templates, modelled after circular, rheumatic, degenerative, and bicuspid lesions, were constructed with equal orifice cross sectional areas in two sizes, 0.2 and 0.7 cm2. These valves were studied in vitro in a flow model of aortic regurgitation, wherein aortic pressure was regulated by varying the height of a column of fluid. Flow, pressure, and velocity were measured, and the coefficient Cc and Cv were calculated from standard equations. MEASUREMENTS AND MAIN RESULTS: Regurgitant volume was assessed at diastolic filling periods of 0.5 and 1.0 s and averaged 15% greater for bicuspid and degenerative as compared to circular or rheumatic valve shapes (p = 0.0001). This difference was accentuated at the shorter diastolic filling time and higher pressure gradient, such that bicuspid lesions allowed 29% more regurgitant flow across the 0.2 cm2 orifice at fluid height of 120 cm over 0.5 s. This difference in regurgitant volume between valve shapes was due to an increased Cc for the bicuspid and degenerative valve shapes, suggesting that they are more efficient orifices than rheumatic or circular valve shapes. CONCLUSIONS: Aortic valve morphology influences regurgitant volume in aortic regurgitation. Specifically, degenerative and bicuspid orifice shapes have a higher contraction coefficient and allow more regurgitant flow than rheumatic or circular orifices at a given driving pressure and diastolic filling time.

Aortic Valve

Medical Practice Support System. A medical practitioner's multimedia workstation.

The United States Navy has developed a computer based Medical Practice Support System (MEPSS) intended for use by medical practitioners working in isolated situations. The system, now being tested in operational settings, emphasizes inexpensive, easily obtained off-the-shelf hardware and specially developed, readily implemented software to provide users with: 1) medical record keeping, 2) an electronic medical library, 3) interactive video instruction programs suitable for continuing medical education, 4) computer based medical diagnosis and treatment assistance, and 5) electronic communications with other facilities. This demonstration emphasizes a user based developmental approach, integration of diverse systems under a single user interface, and portable hardware. The resulting system makes medical information needed by practitioners instantly available at the time of a patient encounter, whenever and wherever that encounter may occur. Making clinically valuable information immediately available, MEPSS demonstrates how practitioners can use computers to help their own efforts to improve patient care quality and efficiency.

Decision Making, Computer-Assisted

Catheter coatings, blood flow, and biocompatibility.

Thrombus forms on catheters and other indwelling synthetic materials. Systemic heparin infusion decreases, but does not eliminate thrombus formation. The day is approaching when systemic heparinization may no longer be indicated to suppress catheter thrombogenesis. Passivation of catheters by heparin immobilization is not yet perfected, but progress is being made. A clearer picture is emerging of the factors that influence the activation of host defenses at foreign surfaces. As this occurs, new materials and surface finishes that take advantage of specific steps in the blood-foreign material interaction are being developed. Surfaces that either inhibit general protein adsorption or promote albumin adsorption appear to possess substantially improved biocompatibility.

Biocompatible Materials

Aortic valve morphology: an important in vitro determinant of proximal regurgitant jet width by Doppler color flow mapping.

In vitro and in vivo studies suggest that proximal aortic regurgitant jet width on Doppler color flow mapping predicts severity of aortic regurgitation. The influence of aortic valve morphology on proximal regurgitant jet width has not been studied. Despite equal cross-sectional area, differences in aortic valve morphology may influence regurgitant jet width and thus estimates of severity of aortic regurgitation. Aortic valve simulations representing degenerative, rheumatic and bicuspid valves as well as a circle in two cross-sectional areas (0.2 cm2 and 0.7 cm2) were placed in a flow model using two gradients (50 and 100 mm Hg) to produce simulated aortic regurgitant jets. Flow maps were obtained from parasternal and apical positions with color gain, frames per second, low velocity reject and depth held constant. The mean of three regurgitant jet widths for each shape, size and gradient were compared by three factor analysis of variance. Aortic valve morphology significantly affected regurgitant jet width in both parasternal and apical views (p = 0.0001 by analysis of variance) with bicuspid shapes producing regurgitant jet widths significantly different from all other shapes. Valve area also consistently significantly influenced proximal regurgitant jet width (p = 0.0001) in both views. Initial pressure gradient was less important. It is concluded that in an in vitro flow model aortic valve morphology introduces significant variability in the measurement of proximal regurgitant jet widths independent of orifice cross-sectional area. Estimates of severity of aortic regurgitation may therefore be influenced considerably by aortic valve morphology.

Analysis of Variance

Fabrication and characterization of small-diameter vascular prostheses.

We have developed a process to fabricate polyurethane vascular grafts of various dimensions and porosities in our laboratory. A primary feature of the presented fabrication technique is the ability to control surface porosity and roughness, and bulk mechanical properties. The method is based on the spray application of a fine mixture of polymer solution and nitrogen gas bubbles onto a lathe-mounted mandrel. The technique was successfully tested with Tecoflex, a linear segmented aliphatic polyurethane. Other urethane polymers can be used as well. Several polymer coats are applied in a semiautomated process, at the end of which the polymer coating is dried and the tube is slipped off the mandrel. It is the purpose of this paper to describe the fabrication process and present results of the evaluation of grafts. Wall structure was evaluated using scanning electron microscopy and compliance was measured in a specially designed testing apparatus. We developed methods to quantify kink resistance and suture retention capacity of the grafts. These characteristics were correlated with graft fabrication variables: mandrel rpm, horizontal speed of the spray nozzle, gas and polymer solution flow rates. We were able to routinely produce 3-6-mm-ID grafts with 0.5-1.2-mm wall thickness and average bulk pore sizes of 10-250 microns; the wall porosity could be varied between 30 and 70%. Compliance values of the grafts were comparable with corresponding values of carotid and femoral arteries of dogs.

Biocompatible Materials

The effect of mannitol and dopamine on the renal response to thoracic aortic cross-clamping.

Postoperative renal failure and insufficiency are important complications of operations that require thoracic aortic cross-clamping. Successful application of pharmacologic methods to protect renal function would be clinically useful. The ability of mannitol and dopamine to prevent renal dysfunction in a canine model of thoracic aortic cross-clamping was studied. Twenty animals were divided into four equal groups, and all underwent thoracic aortic cross-clamping for 60 minutes. An intra-aortic infusion of saline (control), mannitol, dopamine, or mannitol plus dopamine was started before, and continued during, the period of aortic occlusion. Glomerular filtration rate was significantly depressed 60 minutes after clamp release, and although there was some recovery in treated animals 150 minutes after clamp release, it remained significantly decreased (52% to 73% of baseline values, p less than 0.01). Renal blood flow was significantly reduced 60 minutes after clamp release, and there was no recovery in any group at 150 minutes (38% to 56% of baseline values, p less than 0.01). No significant differences in osmolar clearance or fractional excretion of sodium were evident between groups. These data reveal that the profound reductions in glomerular filtration and renal blood flow induced by thoracic aortic cross-clamping were not attenuated by mannitol or dopamine and suggest that efforts to protect renal function should be directed toward improving renal blood flow in the post-clamp period.

Acute Kidney Injury

Fluorescence lifetime measurements using total internal reflection fluorimetry: evidence for a conformational change in albumin adsorbed to quartz.

We have modified the total internal reflectance fluorimetry (TIRF) method to determine, indirectly, quantum fluorescence yield and thus infer structural changes of adsorbed plasma proteins. We employed a frequency multiplied Nd:YAG pulse laser to excite tryptophan residues of bovine serum albumin (BSA), measuring the resulting fluorescence lifetimes. BSA adsorbed on quartz was investigated at normal pH and under acidic (pH 3.8) conditions at which albumin shape change has been established in bulk solution. Albumin adsorbed at pH 7.2 has a slightly lower lifetime than the bulk solution value, reflecting a population of both native and isomerized forms. Gently washing the adsorbate surface significantly reduces fluorescence lifetime, suggesting retention of more tenacious, conformationally altered molecules. Vigorous washing further reduces fluorescence lifetimes to values close to those obtained in bulk under acidic conditions. Similar alterations in fluorescence lifetimes were observed for heat-denatured albumin. These results support the hypothesis that adsorbed albumin exists in the form of a two-layer deposit, each with a possibly different structure. A loosely held layer, consisting of BSA microaggregates and including partially unfolded molecules, exists on the undisturbed surface and is partially removed by gentle washing. Vigorous washing removes all but the most tightly held protein, which exists in a possibly further unfolded configuration. The decrease in fluorescence lifetime of adsorbed BSA implies a corresponding change in quantum yield. A change in quantum yield of BSA tryptophan fluorophors implies that measuring adsorbed protein concentration by intrinsic fluorescence is unreliable.

Adsorption

Albumin adsorption and retention on C18-alkyl-derivatized polyurethane vascular grafts.

The short-term albumin affinity and thrombo-resistance of a polyether polyurethane vascular graft have been improved. The method is based on the C18 alkylation of the polymer. Thrombus formation by a planimetric technique and albumin retention on wire-reinforced polyurethane tubes, both C18 alkylated and untreated, were measured in short-term (4-h) exposure at femoral arterial sites in the dog. 125I-Albumin was preabsorbed on tubes and then exposed to blood for successive 2-h periods. Albumin uptake on alkylated tubes prior to blood exposure and retention following 2 h of blood exposure were significantly greater than on controls. Following a fast desorption phase in blood, the remaining albumin was more slowly desorbed from alkylated than from control tubes. Reincubation with albumin and blood reexposure produced a similar tendency, suggesting blood conditioning does not reduce the albumin affinity-enhancing property of C18 alkylation in the short term. Blood-preconditioning experiments suggested endogenous albumin has a high affinity for the C18-alkylated surface. Scanning electron microscopic examination showed thrombus and platelet densities were higher on control than on alkylated surfaces. These results suggest in vivo albumin affinity is increased for C18-alkylated polyurethane, which may be linked to decreased thrombus formation on these surfaces.

Adsorption

Influence of endogenous albumin binding on blood-material interactions.

A method has been developed to enhance the albumin affinity of a number of medical polymers, based on alkylation of the surface with straight-chain 16- or 18-carbon alkyl groups. This method has been demonstrated to induce the rapid binding of albumin from single and binary protein solutions, from plasma, and apparently, from whole blood. The bound albumin resists fluid shear or chemically induced desorption. Fibrinogen adsorption is inhibited in vitro and in vivo. Complement protein C3 activation from plasma is inhibited. Fibrin formation and platelet aggregation is inhibited in short-term in vivo experiments. Long-term catheter implant studies suggest that the C18 alkylation is more effective than most, if not all, currently available treatments for the retention of a clean, biocompatible, blood-contacting surface. No data have been obtained to date that conflict with the hypothesis that a renewable albumin layer, so formed, blocks the adsorption or conformational alteration of plasma proteins that otherwise might initiate or participate in various host defenses.

Animals