Biomedical subjects

C R Ethier

Publications and source records attributed to C R Ethier.

At least 37 records · Page 2Linked to original sources

PubMed1997

Factors affecting the pores of the inner wall endothelium of Schlemm's canal.

PURPOSE: A linear relationship between the density of pores in the inner wall of Schlemm's canal and aqueous outflow facility has been reported previously in a study in which investigators examined only eyes fixed at constant pressure, so that fixative flow rates differed from eye to eye. Because pores may form as a function of flow rate, the purpose in the current study was to verify the previous findings, using constant flow perfusions. METHODS: Outflow facility was measured in enucleated human eyes. Eyes were fixed under either constant flow or constant pressure conditions, microdissected to expose the inner wall of Schlemm's canal, and prepared for scanning electron microscopy. The density and diameter of pores in the inner wall were measured. RESULTS: Statistical analysis showed no correlation between outflow facility and either the density or the diameter of pores. Pore density decreased significantly during the hours after death. Examining only eyes for which experimentation was started within 20 hours of death, we found that pore density increased significantly with the volume of fixative that had been perfused through the outflow pathway. CONCLUSIONS: The correlation found by Allingham et al between outflow facility and pore density in the inner wall endothelium was not confirmed. However, the relationship between pore density and volume of fixative perfused is consistent with and may be responsible for the finding in the previous study. Because fixation conditions can influence the apparent pore density in the inner wall endothelium significantly, the conclusion reached previously, that pores contribute only 10% of the aqueous outflow resistance, may require reevaluation.

Adolescent↗

PubMed1996

Schlemm's canal and primary open angle glaucoma: correlation between Schlemm's canal dimensions and outflow facility.

The purpose of the study was to examine the correlation between outflow facility and morphometric measurements of Schlemm's canal (SC) in normal and glaucomatous human eyes. Outflow facility was measured in ten normal and five glaucomatous (POAG) human eyes prior to perfusion-fixation at a pressure of 15 mmHg. Two separate sections per quadrant (eight sections per eye) were analysed using a morphometric analysis system. SC cross sectional area, perimeter, and inner wall length were measured. Inner wall endothelial nuclei were counted. When pooled data were examined, a statistically significant correlation was found between facility and SC area (P < or = 0.01). Most importantly, POAG eyes had a significantly smaller SC cross-sectional area, SC perimeter and SC inner wall length compared to normal eyes. If examined as a reduction in SC filtering area, this decrease in SC inner wall length alone could account for approximately 41-55% of the difference in outflow facility observed between normal and POAG eyes. The dimensions of Schlemm's canal in glaucomatous human eyes were significantly smaller than those in normal eyes. This reduction in SC dimensions may account for approximately half of the decrease in outflow facility observed in POAG eyes.

Aged↗

PubMed1996

MR measurement and numerical simulation of steady flow in an end-to-side anastomosis model.

Magnetic resonance phase contrast velocity imaging ('MR PC velocimetry') is a powerful tool for measuring blood velocity. While it has been demonstrated that MR PC velocimetry can accurately measure velocity profiles in simple, unidirectional flows, errors can arise when measuring the more complex, multidirectional flows of clinical importance. In this work, we have compared MR PC velocity measurements with numerical simulations of steady flow in a physiologically relevant model of an end-to-side anastomosis, which produces many of the complex flow features expected in vivo. MR PC velocity profiles, measured using both 2D and 3D pulse sequences, showed very good agreement with numerically computed profiles, although at 2D PC data showed slightly larger errors than the 3D PC data in regions of high accelerations and oblique flow, likely due to displacement artifacts. We conclude that, under ideal conditions, MR phase contrast velocimetry can measure complex flow patterns to within 15% accuracy, but that care should be taken when using 2D pulse sequences to measure such complex flows.

Anastomosis, Surgical↗

PubMed1996

Particle volumetric residence time calculations in arterial geometries.

The quantification of particle (platelet) residence times in arterial geometries is relevant to the pathogenesis of several arterial diseases. In this manuscript, the concept of "volumetric residence time" (VRT) is introduced. The VRT takes into account where particles accumulate and how long they remain there, and is well-suited to characterizing particle distributions in the complex geometries typical of the cardiovascular system. A technique for the calculation of volumetric residence time is described, which assumes that platelets are neutrally buoyant passive tracer particles, and which tracks small Lagrangian fluid elements containing a uniform concentration of platelets. This approach is used to quantify particle (platelet) residence times in the region of a modeled stenosis with a 45 percent area reduction. Residence time distributions are computed for a representative population of platelets, and for a subpopulation assumed to be "activated" by exposure to shear stresses above a threshold value. For activated platelets, high particle residence times were observed just distal to the apex of the stenosis throat, which can be explained by the presence of high shear stresses and low velocities in the throat immediately adjacent to the vessel wall. Interestingly, the separation zone distal to the stenosis showed only modestly elevated residence times, due to its highly mobile and transient nature. This calculation demonstrates the utility of the VRT concept for cardiovascular studies, particularly if a subpopulation of all particles is to be tracked. We conclude that the volumetric residence time is a useful tool.

Algorithms↗

PubMed1995

Retroperfusion studies of the aqueous outflow system. Part 2: Studies in human eyes.

PURPOSE: To extend the retroperfusion technique to allow the delivery of drugs into Schlemm's canal in enucleated human eyes and to use this technique to gain insights into the function of the inner wall of Schlemm's canal. METHODS: Using our previously developed retroperfusion technique, the anterior chamber of enucleated human eyes was held at a small negative pressure (-0.75 mm Hg), and fluid was allowed to flow retrograde from the limbal vessels, through the collector channels, and into Schlemm's canal. In this manner, the sulfhydryl agent N-ethyl maleimide (NEM) or the fixative agent glutaraldehyde was delivered to the inner wall of Schlemm's canal in normal and glaucomatous human eyes. Facility changes caused by retroperfusion were measured and correlated with histologic studies of the inner wall of Schlemm's canal. RESULTS: Retroperfusion effectively delivers fluid from the scleral surface into the lumen of Schlemm's canal. Retroperfusion with vehicle alone does not alter facility or change outflow pathway morphology. Retroperfusion with NEM causes an approximately 35% facility increase and concomitant inner wall openings. Retroperfusion with glutaraldehyde in normal eyes and eyes with primary open-angle glaucoma causes a facility decrease of 53% and 64%, respectively, and localized fixation of the inner wall of Schlemm's canal. The magnitude of the facility changes caused by retroperfusion were similar to those seen using conventional forward perfusion of NEM and glutaraldehyde. CONCLUSIONS: Retroperfusion is a viable technique for the delivery of drugs or other agents into Schlemm's canal in enucleated human eyes. Retroperfusion-induced changes in outflow facility are correlated strongly with morphologically observed alterations in inner wall structure. The majority of outflow resistance is localized to the inner wall of Schlemm's canal or the immediately adjacent 10-microns region of the juxtacanalicular tissue in normal eyes and in eyes with primary open-angle glaucoma. Inner wall giant vacuoles and pores likely persist for sometime, even after fixation at zero or negative pressure.

Anterior Eye Segment↗

PubMed1994

The effect of wall distensibility on flow in a two-dimensional end-to-side anastomosis.

The development of intimal hyperplasia at the distal anastomosis is the major cause of long-term bypass graft failure. To evaluate the suspected role of hemodynamic factors in the pathogenesis of distal intimal hyperplasia, an understanding of anastomotic flow patterns is essential. Due to the complexity of arterial flow, model studies typically make simplifying assumptions, such as treating the artery and graft walls as rigid. In the present study this restriction is relaxed to consider the effects of vessel wall distensibility on anastomotic flow patterns. Flow was simulated in an idealized 2-D distensible end-to-side anastomosis model, using parameters appropriate for the distal circulation and assuming a purely elastic artery wall. A novel numerical approach was developed in which the wall velocities are solved simultaneously with the fluid and pressure fields, while the wall displacements are treated via an iterative update. Both the rigid and distensible cases indicated the presence of elevated temporal variations and low average magnitudes of wall shear stress at sites known to be susceptible to the development of intimal hyperplasia. At these same sites, large spatial gradients of wall shear stress were also noted. Comparison between distensible-walled and corresponding rigid-walled simulations showed moderate changes in wall shear stress at isolated locations, primarily the bed, toe and heel. For example, in the case of a distensible geometry and a physiologic pressure waveform, the heel experienced a 38 percent increase in cycle-averaged shear stress, with a corresponding 15 percent reduction in shear stress variability, both relative to the corresponding values in the rigid-walled case.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

PubMed1994

Deformation of the lamina cribrosa by elevated intraocular pressure.

The purpose of this study was to determine the mechanical response of the lamina cribrosa (LC) to elevated intraocular pressure (IOP) so as to identify possible mechanisms of optic nerve damage in early glaucoma. Ten pairs of normal human eyes were fixed after 24 hours' exposure to 50 mm Hg pressure (experimental eyes) or 5 mm Hg pressure (contralateral control eyes). Photomicrographs of the central region of the optic nerve head (ONH) were taken to examine the LC morphologically and to measure the dimensions of the LC. It was found that elevated IOP caused the LC to deflect posteriorly without affecting its thickness. The majority of the posterior displacement in the LC occurred near the periphery of the ONH. This shape change is consistent with a model of force distribution within the LC in which shear stresses are dominant; such stresses are maximal at the periphery and minimal at the centre of the ONH. These findings support a model in which mechanical forces, specifically shearing stresses within the peripheral lamina, play a direct role in the pathology of glaucomatous optic neuropathy.

Aged↗

PubMed1993

A numerical simulation of flow in a two-dimensional end-to-side anastomosis model.

In order to understand the possible role that hemodynamic factors may play in the pathogenesis of distal anastomotic intimal hyperplasia, we carried out numerical simulations of the flow field within a two-dimensional 45 degree rigid-walled end-to-side model anastomosis. The numerical code was tested and compared with experimental (photochromic dye tracer) studies using steady and near-sinusoidal waveforms, and agreement was generally very good. Using a normal human superficial femoral artery waveform, numerical simulations indicated elevated instantaneous wall shear stress magnitudes at the toe and heel of the graft-host junction and along the host artery bed. These sites also experienced highly variable wall shear stress behavior over the cardiac cycle, as well as elevated spatial gradients of wall shear stress. These observations provide additional evidence that intimal hyperplasia may be correlated to wall shear stresses over the cardiac cycle, high wall shear stress gradients, or a combination of the three. The limitations of the present work (especially in regard to the two-dimensional nature of the flow simulations) are discussed, and results are compared to previous observations about distal anastomotic intimal hyperplasia.

Anastomosis, Surgical↗

PubMed1993

An improved ocular perfusion system.

We describe the design, construction and testing of an improved ocular perfusion system for outflow facility measurement. The essential feature of the system is the measurement of a differential pressure across a calibrated length of tubing, which provides a stable and accurate reading of facility and hence also of flowrate. Perfusion of calibrated lengths of tubing showed excellent accuracy, while perfusions of enucleated eyes showed very low noise levels. The system is relatively inexpensive, easy to construct and maintain, insensitive to vibrations and other noise, and accurate. It is therefore felt to be superior to conventional "hanging bucket" ocular perfusion systems.

Animals↗

PubMed1993

Retroperfusion studies of the aqueous outflow system. Part I: Evaluation of technique using N-ethyl maleimide.

PURPOSE: The goal of this study was to develop a new technique to deliver drugs or other agents to the lumen of the angular aqueous plexus/Schlemm's canal (AAP/SC) while bypassing the trabecular meshwork, thereby gaining insight into AAP/SC inner wall function. METHODS: The anterior chamber is held at a small negative pressure and fluid is allowed to flow retrograde from the limbal vessels, through the collector channels, and into the AAP/SC ("retroperfusion"). Facility measurements are combined with histologic and tracer studies in bovine eyes. RESULTS: (1) Retroperfusion with a saline solution does not alter facility or change outflow pathway morphology; (2) fluid is able to move retrograde from the scleral surface and enter the lumen of the AAP; and (3) retroperfusion with N-ethyl maleimide causes a dose-dependent increase in washout rate and concomitant inner wall breaks. CONCLUSIONS: It is hypothesized that the observed increase in washout is due to leakage of extracellular materials through breaks in the inner wall.

Animals↗

PubMed1992

Visualization of complex flow fields, with application to the interpretation of colour flow Doppler images.

The interpretation of colour flow Doppler images in regions of complex flow can be difficult. To aid in such interpretations, we have developed software which accepts as input the results of a fluid flow simulation program and produces simulated colour flow Doppler images on a workstation. This allows direct comparison between well-described flow fields and colour flow Doppler images. Application of this approach is demonstrated for flow in a two-dimensional model of a distal graft-to-vessel anastomosis, and the interpretation of the results for three-dimensional flows is briefly discussed. In addition, a method for presenting two-dimensional (vectorial) velocity data via colour coding is presented.

Algorithms↗

PubMed1992

The relationship between pore density and outflow facility in human eyes.

The inner wall (IW) endothelial lining of Schlemm's canal was examined in six normal human eyes and four eyes with primary open angle glaucoma (POAG). Outflow facility was measured using constant pressure perfusion at 15 mmHg, eyes were fixed at 15 mmHg, and the IW endothelial lining was isolated and examined by scanning electron microscopy. Pore density, pore diameter, and bulge density were recorded by quadrant, and pore size and density were used to estimate IW endothelial facility, resistance, and hydraulic conductivity (facility per unit area). In POAG eyes, pores were less common (489 +/- 172 vs 1437 +/- 423 pores/mm2; P less than .005) and appeared to be more unevenly distributed than in normal eyes. A regional analysis of pore density (by quadrant) failed to detect a significant difference between quadrants of normal or POAG eyes. Pore density was correlated with measured outflow facility in normal eyes alone (P less than .02) and when normal eyes were pooled with POAG eyes (P less than .001). The percentage of total resistance attributed to the IW endothelium was 5.8% in normals compared to 9.5% in POAG eyes. This indicates there is a greater pressure drop across the IW endothelium in POAG eyes, suggesting that an intrinsic difference in IW endothelial function exists between normal and glaucomatous eyes. However, this difference alone does not account for the decreased outflow facility in POAG eyes. IW endothelial hydraulic conductivity is markedly higher than that of other vascular endothelia. We hypothesize that this may protect the IW endothelial lining of Schlemm's canal from mechanical stress induced by the relatively high rate of transcellular fluid flow.

Aged↗

PubMed1992

Modulation of outflow resistance by the pores of the inner wall endothelium.

The juxtacanalicular connective tissue (JCT) is widely believed to generate the bulk of aqueous humor outflow resistance, while the pores of the inner wall endothelium are thought to generate at most 10% of this resistance in humans. However, the hydrodynamic interaction of these two components of the aqueous outflow system, which arises because of their spatial proximity, has only recently been considered. Modelling the JCT as a homogeneously distributed porous material upstream of a low porosity filter (the inner wall endothelium), the pores of the inner wall are found to cause a "funneling effect," in which the aqueous humor flows preferentially through those regions of the JCT nearest the inner wall pores. The bulk of the pressure drop occurs in the immediate proximity of the pores (within three pore radii). This greatly increases the apparent flow resistance of the JCT. For a set of parameters characterizing the normal eye, this enhancement is approximately 30-fold. The conclusion of this study is that changes in inner wall porosity may greatly affect aqueous outflow resistance, despite the low flow resistance of the inner wall pores themselves.

Aqueous Humor↗

PubMed1991

Computer simulation of blood flow patterns in arteries of various geometries.

The purpose of this study is to illustrate the application of computer simulation to the study of blood flow through arteries and to demonstrate the relationship between geometry of the vessels and local flow patterns. A finite element computer program was developed to simulate steady and pulsatile blood flow by solving the continuity and Navier-Stokes equations. The accuracy of the computational method has been confirmed by comparing the numeric results to analytic solutions and to published experimental data from physical models. The results are presented as plots of the velocity vectors, streamlines, and pressure contours. The computational model has been applied to illustrate flow patterns in the following situations: pulsatile flow in a cylindric artery and an artery with an axisymmetric stenosis, steady flow in cylindric arteries with stenoses of varying severity and with different flow rates, steady flow in an artery containing a fusiform aneurysm, steady flow in a two-dimensional model of a symmetric Y-shaped bifurcation, and steady flow in a two-dimensional model of the carotid bifurcation. Regions that are commonly associated with arterial disease often coincide with zones of reversed or stagnant flow. In conclusion, the versatility and feasibility of computational simulation of blood flow is illustrated by this study. Although this mathematic model is a simplification of the real flow phenomena, it yields results that provide useful insights into the understanding of local blood flow patterns for a variety of complex geometries.

Aneurysm↗

PubMed1991

Effects of hydrogen peroxide-induced oxidative damage on outflow facility and washout in pig eyes.

Previous studies show that hydrogen peroxide (H2O2) is present in the aqueous humor of many species and is capable of affecting outflow facility in animal model experiments. To study the hypothesis that oxidative damage to the outflow pathway may play a role in the pathogenesis of primary open-angle glaucoma, 3 mM H2O2 with 20 mM 3-aminotriazole and 1 mM carmustine (BCNU) in Dulbecco's phosphate-buffered saline (DPBS) was perfused into enucleated pig eyes at constant pressure. Baseline and experimental perfusions were done at two different pressures (7.5 and 30 mm Hg) to study the effect of pressure on the response to oxidative damage. Outflow facility in the baseline experiments (with DPBS only) was observed to increase nonlinearly with time during the perfusions, but could be linearized if plotted as a function of the volume perfused. Thus, a term "volumetric washout" (W) was introduced and defined as the fractional rate of change of outflow facility with respect to the volume perfused. This quantity was found to be independent of pressure in the baseline studies. Perfusion of H2O2 and inhibitors increased W at 7.5 mm Hg but decreased W at 30 mm Hg. These results indicate that oxidative damage increases outflow facility at normal pressure but decreases it at elevated pressure, suggesting that elevated pressure may increase the susceptibility of the outflow pathway to this form of insult.

Animals↗

PubMed1990

Steady and pulsatile flow fields in an end-to-side arterial anastomosis model.

We investigated the flow field within a rigid-walled in vitro model of an end-to-side 45 degree anastomosis in an attempt to identify possible hemodynamic factors that may contribute to the pathogenesis of distal anastomotic intimal hyperplasia. A high-resolution photochromic tracer technique was used to visualize the flow in orthogonal planes and to determine the axial wall shear stress profiles for both steady and pulsatile flows over a range of physiologically relevant conditions. The flow field showed qualitative similarities to those seen in curved vessel: rapidly moving fluid from the graft section affects the bed of the host vessel, that is, the wall opposite the anastomosis, eventually advancing down the host vessel in a spiraling motion. A small mobile separation zone was noted at the toe of the anastomosis. Comparison of wall shear stress profiles with previously reported preferential sites for the development of intimal hyperplasia supported a low wall shear stress and/or flow separation pathogenesis hypothesis. One notable exception was the bed of the host artery that appeared to be subjected to a complex hemodynamic environment.

Arteriovenous Shunt, Surgical↗

PubMed1989

Two-dimensional gel electrophoresis of calf aqueous humor, serum, and filter-bound proteins.

Recent studies have demonstrated that bovine and primate aqueous humor (AH) obstruct flow when perfused through artificial membranes with pore sizes similar to those found in the aqueous outflow pathway. Proteinaceous AH components were implicated in this phenomenon, which is not observed with serum diluted to comparable protein concentrations. In this study, we used two-dimensional gel electrophoresis to characterize the protein composition of calf AH and to identify those proteins binding to the filters and presumably causing this obstruction. Comparison of AH and serum under denaturing conditions showed quantitative and qualitative differences in their protein content. Among the most important: AH was seen to possess two protein subunit trains (approximately 28 kD and approximately 48 kD) not found in serum and two trains (approximately 28 kD and approximately 80 kD) with additionally charged components not found in serum. Serum, on the other hand, possesses one train (approximately 80-90 kD) not found in AH as well as a slightly greater relative amount of high-molecular weight protein subunits. The finding that hydrophobic filters retain more protein components than do hydrophilic filters suggests that the type and amount of protein adhering to them is determined largely by hydrophobic interactions. Whether such interactions occur in the outflow system, and if so, how they may relate to aqueous drainage remains to be determined.

Animals↗

PubMed1989

Further studies on the flow of aqueous humor through microporous filters.

It has recently been shown that aqueous humor is able to obstruct flow through Nuclepore polycarbonate filters having flow dimensions similar to those found in the juxtacanalicular tissue (JCT). We undertook studies designed to identify the component(s) of aqueous humor responsible for this obstruction and to determine the mechanism of blockage. We conclude that aqueous humor contains two components (one of which is specific to aqueous) which, when simultaneously present, hydrophobically bind to microporous filters and lead to filter blockage. Some implications for aqueous humor flow through the JCT are briefly discussed.

Animals↗