Biomedical subjects

W R Wagner

Publications and source records attributed to W R Wagner.

45 records · Page 3Linked to original sources

PubMed1990

Local thrombin synthesis and fibrin formation in an in vitro thrombosis model result in platelet recruitment and thrombus stabilization on collagen in heparinized blood.

The role of the local synthesis of thrombin in platelet recruitment and thrombus stabilization in heparinized blood was examined in vitro. Mural thrombosis was visualized and measured in a thin, rectangular, collagen-coated capillary under controlled rheological conditions by using fluorescence digital videomicroscopy and fluorescence microphotometry. Thrombin activity was inhibited in heparinized blood by the synthetic competitive inhibitor, D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone (FPRCH2Cl), resulting in a marked reduction in the rate of platelet accumulation on collagen surfaces, indicating a role for thrombin in platelet recruitment. Similar although lesser effects were observed by reducing thrombin synthesis with antibodies to factors II and X. To decouple the role of thrombin in platelet recruitment by direct stimulation of platelet activity from its role in thrombus stabilization via fibrin formation, thrombosis was measured in heparinized blood treated with the tetrapeptide glycyl-prolyl-arginyl-proline, which inhibits fibrin monomer assembly into fibrin. The ultimate level but not the initial rate of platelet accumulation was reduced markedly, indicating a role for fibrin in thrombus stabilization against hemodynamic forces. Scanning electron micrographs demonstrated fibrin stands in the heparinized control samples but not in the heparinized samples with glycyl-prolyl-arginyl-proline. These results demonstrate a role for the local action of thrombin synthesized on the surfaces of thrombi even under conditions when the thrombin exerts no bulk effect, such as under heparin anticoagulation. Furthermore, this role appears to be a result of both platelet recruitment and thrombus stabilization.

Amino Acid Chloromethyl Ketones↗

PubMed1989

Phenotypic relationships of scrotal circumference to frame size and body weight in performance-tested bulls.

The objective of this study was to determine if frame size (height) is related to scrotal circumference. A total of 695 bulls (425 Angus, 65 Hereford, 70 Charolais, 135 Simmentals) were tested for postweaning gain in five stations over a period of 1 to 3 years. Variables examined included hip height, weight and scrotal circumference at beginning and completion of a 140-d feeding period. Correlations among these traits, adjusted for age (7 to 10 months at entry), year, station and management were estimated for each breed. Both height and weight were correlated positively with scrotal circumference at the start and the end of the test period in all four breeds. When height and scrotal circumference were adjusted for weight, correlations were negligible, with the exception of end-of-test values for Charolais bulls (-0.26). Negative correlations were obtained between the scrotal circumference at the start of the test and the change in height during the test after adjustment for weight in Angus bulls (-0.18) and in Charolais bulls (-0.15). These small negative phenotypic relationships indicate that a bull's fertility is not seriously reduced by large frame size at the completion of a feedlot performance test. For maximum fertility in bulls, scrotal circumference needs to be evaluated independently of frame size.

Journal Article↗

PubMedDate not supplied

Thrombin activity resides on LVAD Dacron inflow and outflow grafts.

Patients on left ventricular assist devices (LVADs) are at increased risk for thromboembolism, and they experience elevations in platelet release and thrombin activity indices during device implantation. The Dacron grafts that lead from the ventricle to the LVAD and back to the aorta may harbor thrombin activity and protect this thrombin from anticoagulant action. To investigate this possibility, specimens isolated from LVAD grafts at the time of device explantation or implantation were incubated with citrated platelet poor plasma (cPPP), cPPP and 2 U/ml of heparin, cPPP and 2 U/ml of recombinant hirudin (r-hirudin), or cPPP and 50 U/ml of heparin. Thrombin activity was measured by the increase in incubated cPPP fibrinopeptide A (FPA) concentrations over cPPP FPA levels, without material contact. A chromogenic substrate for thrombin verified the effects seen. Thrombin activity was found at comparable levels on both the inflow and outflow LVAD grafts at explantation. This activity was not inhibited by low concentrations of heparin, but 50 U/ml of heparin and 2 U/ml of r-hirudin reduced the activity. At graft implantation (after preclotting), thrombin activity was higher than at explantation, but susceptibility to inhibition by heparin was also significantly greater. These results confirm that the LVAD Dacron grafts harbor surface thrombin activity resistant to anticoagulation that may be a primary source for LVAD thrombogenicity.

Heart Ventricles↗

PubMedDate not supplied

A new fiber optic probe for cellular visualization.

Thrombus formation within artificial organs has been shown, at least in part, to be caused by retarded or stagnant blood flow. The goal of this work was to develop a magnifying fiber optic probe capable of visualizing particle flow and cellular deposition in a physiologically relevant cellular suspension (blood). The probe has minimal cross sectional area to allow for access to confined areas and to minimize flow disturbance. The probe consists of a germanium oxide fiber optic bundle and a gradient index imaging lens. Fluorescent microspheres of 48 microns, 7 microns, and 3 microns in diameter were imaged after deposition on to a cover slip. The flow (1.44 mm/sec) of 3 microns microspheres suspended in buffer alone and with red cell hematocrits of 10%, 25% and 45% were also visualized. To investigate the potential for this probe to detect ongoing thrombosis, fluorescently labeled human platelets were observed depositing on surfaces from a stagnant platelet rich buffer. These initial data suggest that this probe may offer a technique for the visualization of blood cell adhesion on the interior of artificial organs and the local quantification of flow in such devices.

Artificial Organs↗

PubMedDate not supplied

Nitric oxide prevents human platelet adhesion to fiber membranes in whole blood.

During cardiopulmonary bypass or long-term extracorporeal life support, foreign surface induced platelet deposition in the oxygenator causes deterioration of gas exchange. In this study, the authors evaluated the effectiveness of nitric oxide (NO) in reducing the adhesion of platelets in whole blood to the surface of hollow fiber membranes. For this purpose, a test chamber was designed consisting of a gas exchanger with ten mitsubishi multi-layered composite hollow fibers (MHF: 257 mm OD; 203 mm ID; 70 mm length) and a polypropylene tube (16 mm OD; 100 mm length). Pure N2 (control) or nitric oxide (NO) (100 ppm, 200 ppm in N2) were delivered into the test chamber previously filled with 13 ml human whole blood. Platelet counts and platelet factor 4 (PF4), as a measure of platelet activation, were measured before and after either 1 or 2 hr of testing, and fibers were observed under scanning electron microscopic study (SEM) after each experiment. In the control and 100 ppm NO groups, platelet counts decreased and the level of PF4 increased during the 1 hr period. In the 200 ppm NO group, almost no platelet deposition could be observed on the surface of fibers under SEM. In conclusion, NO flow through hollow fiber membranes can markedly reduce platelet adhesion. Additional quantitative studies should define the optimal concentration for this effect and determine if this finding could improve oxygenator function, especially under conditions of long-term support.

Cardiopulmonary Bypass↗

PubMedDate not supplied

Computational simulation of platelet deposition and activation: I. Model development and properties.

To better understand the mechanisms leading to the formation and growth of mural thrombi on biomaterials, we have developed a two-dimensional computational model of platelet deposition and activation in flowing blood. The basic formulation is derived from prior work by others, with additional levels of complexity added where appropriate. It is comprised of a series of convection-diffusion-reaction equations which simulate platelet-surface and platelet-platelet adhesion, platelet activation by a weighted linear combination of agonist concentrations, agonist release and synthesis by activated platelets, platelet-phospholipid-dependent thrombin generation, and thrombin inhibition by heparin. The model requires estimation of four parameters to fit it to experimental data: shear-dependent platelet diffusivity and resting and activated platelet-surface and platelet-platelet reaction rate constants. The model is formulated to simulate a wide range of biomaterials and complex flows. In this article we present the basic model and its properties; in Part II (Sorensen et al., Ann. Biomed. Eng. 27:449-458, 1999) we apply the model to experimental results for platelet deposition onto collagen.

Antithrombin III↗

PubMedDate not supplied

Computational simulation of platelet deposition and activation: II. Results for Poiseuille flow over collagen.

We have previously described the development of a two-dimensional computational model of platelet deposition onto biomaterials from flowing blood (Sorensen et al., Ann. Biomed. Eng. 27:436-448, 1999). The model requires estimation of four parameters to fit it to experimental data: shear-dependent platelet diffusivity and three platelet-deposition-related reaction rate constants. These parameters are estimated for platelet deposition onto a collagen substrate for simple parallel-plate flow of whole blood in both the presence and absence of thrombin. One set of experimental results is used as a benchmark for model-fitting purposes. The "trained" model is then validated by applying it to additional test cases from the literature for parallel-plate Poiseuille flow over collagen at both higher and lower wall shear rates, and in the presence of various anticoagulants. The predicted values agree very well with the experimental results for the training cases, and good reproduction of deposition trends and magnitudes is obtained for the heparin, but not the citrate, validation cases. The model is formulated to be easily extended to synthetic biomaterials, as well as to more complex flows.

Adenosine Diphosphate↗

PubMedDate not supplied

Continued development of the Nimbus/University of Pittsburgh (UOP) axial flow left ventricular assist system.

Nimbus and the University of Pittsburgh (UOP) have continued the development of a totally implanted axial flow blood pump under the National Institutes of Health (NIH) Innovative Ventricular Assist System (IVAS) program. This 62 cc device has an overall length of 84 mm and an outer diameter of 34.5 mm. The inner diameter of the blood pump is 12 mm. It is being designed to be a totally implanted permanent device. A key achievement during the past year was the completion of the Model 2 pump design. Ten of these pumps have been fabricated and are being used to conduct in vitro and in vivo experiments to evaluate the performance of different materials and hydraulic components. Efforts for optimizing the closed loop speed control have continued using mathematical modeling, computer simulations, and in vitro and in vivo testing. New hydraulic blade designs have been tested using computational fluid dynamics (CFD) and flow visualization. A second generation motor was designed with improved efficiency. To support the new motor, a new motor controller fabricated as a surface mount PC board has been completed. The program is now operating under a formal QA system.

Animals↗

PubMedDate not supplied

In vivo performance of a modified CSTi dental implant coating.

Cylindrical dental implants coated with cancellous structured titanium (CSTi) were studied in a dog model. CSTi-2-coated and hydroxyapatite-coated (HA) implants were placed in 8 mongrel dogs. The porosity of the CSTi-2 coating was 9% less than that of the previously studied CSTi-1, resulting in greatly improved mechanical strength and cosmetic appearance. A slightly lower level of bone ingrowth was observed for CSTi-2 than for CSTi-1. However, the in vivo attachment strength of the CSTi-2 coating was comparable both to CSTi-1 and to an HA-coated control after 8 weeks. Measured porosity is technique dependent; digital analysis of in vitro samples yielded higher porosity values than in vivo histology cross sections.

Animals↗