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Biomedical subjects

S Weinbaum

Publications and source records attributed to S Weinbaum.

At least 73 records · Page 4Linked to original sources
PubMed1981

A model of epithelial water transport. The corneal endothelium.

To try to understand how an epithelial tissue can transport water between bathing solutions of equal tonicity and how intracellular solute and protein concentration are related to the structural specialization of the cell membrane at its apical, basal, and lateral margins, we have formulated and solved, using approximate analytical techniques, a new model which combines the detailed transport of local osmotic flow in extracellular channel with the multicompartment approach of thermodynamic models requiring the overall conservation of water and solute for the entire cell layer. Thus, unlike most previous models, which dealt exclusively with either the average properties of the cell layer or the local transport in the extracellular channel, we are able to solve simultaneously for the interaction of the cell with its environments across its apical, basal, and lateral cell membranes as well as the detailed transport in the extracellular channel. The model is then applied to corneal endothelium to obtain new insight into the water flow movement in this tissue under in vitro and in vivo conditions. Then in vitro solution shows that the cell at 297 mosmol/liter is slightly hypotonic to the 300-mosmol/liter external bathing solutions which drive water equally out both the aqueous (apical) and stromal (basal) cell faces. This water is replaced from the extracellular channel. There is a net flow of water because more water enters the channel through its open stromal end than through the higher resistance tight junction. In vivo, the solution predicts that the stromal swelling pressure forces water through the tight junctions towards the stroma so that there is no net flow. The interesting new features of our solution are the water recirculation pattern and the role of the osmotically active proteins in making the cell hypertonic relative to the channel.

Animals↗
PubMed1981

Vesicle transport in arterial endothelium and the influence of mechanical factors on macromolecular permeability.

The time-dependent transport of labeled vesicles in arterial endothelium has been modeled, taking into account the space-varying electrodynamic and hydrodynamic forces and the steric hindrance of vesicle attachment by the already attached vesicles. With the aid of laboratory model experiments to assess the steric hindrance effect, theoretical computation has been made on time-dependent labeled vesicle concentration profiles, and the results agree reasonably well with the published experimental data. Oscillatory length variations (5-10 Hz for 15 min) and elevation of transmural pressure (from 0-100 and 200 mmHg) caused increases in 125I-albumin uptake by the canine common carotid artery. Theoretical computations based on ultrastructural determination of free vesicle density indicate that there was negligible enhancement of vesicle diffusion by these mechanical disturbances. The increases in albumin uptake following length oscillation and pressure elevation to 100 mmHg were accompanied by increases in luminal surface area, and the albumin permeability remained unchanged. The albumin permeability was elevated following pressure elevation to 200 mmHg, and this was attributable to (a) a decrease in transendothelial diffusion distance, and (b) facilitation of vesicle loading into the vesicles.

Animals↗
PubMed1981

Diffusion of macromolecules across the arterial wall in the presence of multiple endothelial injuries.

In this paper, the two-phase arterial wall model developed by Weinbaum and Caro [2] has been extended to obtain analytic solutions for the steady-state flux, uptake and concentration of macromolecules in the arterial wall due to the presence of periodically dispersed local sites of enhanced permeability. In the endothelial cell layer these sites are believed to be associated with the dying and regeneration of individual cells in the endothelial monolayer. Nir and Pfeffer [9] obtained similar solutions for a single dying cell in an otherwise undamaged endothelial cell layer. However this model requires that multiple cell turnover sites be spaced sufficiently far apart such that no interaction between neighboring sites takes place and hence cannot be applied to closely spaced endothelial injuries which have been observed experimentally in physiological studies. The theoretical predictions of the present model compare very favorably with experimental results for the enhanced uptake found in blue versus white areas reported in morphological studies of the endothelial surface (Bell, et al. [10, 11]).

Animals↗
PubMedDate not supplied

A fiber matrix model for fluid flow and streaming potentials in the canaliculi of an osteon.

A theoretical model is developed to predict the fluid shear stress and streaming potential at the surface of osteocytic processes in the lacunar-canalicular porosity of an osteon when the osteon is subject to mechanical loads that are parallel or perpendicular to its axis. The theory developed in Weinbaum et al. (31) for the flow through a proteoglycan matrix in a canaliculus is employed in a poroelastic model for the osteon. Our formulation is a generalization of that of Petrov et al. (17). Our model predicts that, in order to satisfy the measured frequency dependence of the phase and magnitude of the SGP in macroscopic bone samples, the fiber spacing in the fluid annulus must lie in the narrow range 6-7 nm typical of the spacing of GAG sidechains along a protein monomer. The model predictions for the local SGP profiles in the osteon agree with the experimental observations of Starkebaum et al. (24). The theory predicts that the pore pressure relaxation time, tau d, for a 150-300 microns diameter osteon with the foregoing matrix structure is approximately 0.03-0.13 sec, and that the amplitude of the mean fluid shear stress on the membrane of the osteocytic process at the mean areal radius of the osteon has a maximum at 28 Hz if tau d = 0.06 sec. This maximum, which is independent of the magnitude of the loading, could be important in vivo since the recent experiments of Turner et al. (28) and McLeod et al. (15) have a peak in the strain frequency spectrum between 20 and 30 Hz that also appears to be independent of the type (magnitude) of loading. Numerical predictions for the amplitude of the average fluid shear stress on the osteocytic membrane at the mean areal radius of the osteon show that the fluid shear stress associated with the low amplitude 20-30 Hz spectral strain component is at least as large as the average fluid shear stress associated with the high amplitude 1 Hz stride component, although the latter loading is an order of magnitude larger, and has a magnitude that lies within the middle of the range, 6-30 dynes/cm2, where fluid shear stresses in tissue culture studies with osteoblast monolayers have elicited an intracellular Ca++ response (31). The implications of these results for intracellular electrical communication are discussed.

Biomechanical Phenomena↗
PubMedDate not supplied

A new approach for predicting the enhancement in the effective conductivity of perfused muscle tissue due to hyperthermia.

This study attempts to measure the hyperthermic response of individual microvessels in skeletal muscle tissue subject to local heating and then to predict the enhancement in thermal conductivity that results from the observed changes in vascular diameter and flow. In contrast to existing studies, which have tried to relate changes in tissue thermal conductivity to local blood perfusion using thermal clearance and self-heated thermistor techniques, we have developed a two-dimensional muscle tissue preparation in which the hyperemic response has been quantified by measuring the in vivo changes in diameter and blood flow of 1A to 4A generation vessels of rat cremaster muscle when the temperature was raised in 2 degrees increments from 34 to 42 degrees C. Only 3A and 4A vessels showed vasodilation when subject to hyperthermia, indicating that the measured increase in flow in the 1A and 2A vessels was the result of a decrease in downstream resistance. Our cremaster muscle preparations have also been used to obtain the first detailed anatomic measurements of the number density and length of countercurrent vessel pairs between 50-200 microns diameter. These combined measurements have been used to establish the limits of validity of the Weinbaum-Jiji theory. Our experimental data indicate that the Weinbaum-Jiji expression for keff is valid in cremaster muscle and cat mesentery tissue for both normal and hyperthermic conditions provided the largest vessels are < 200 microns in diameter. The theory predicts that significant enhancements in keff start to occur for vessels that are 70 microns in diameter or larger, that a 2.5-fold increase in keff can be achieved for a maximally dilated 200 microns diameter 1A vessel pair in cremaster muscle of larger rats, and a 6-fold increase is predicted for maximally dilated 200 microns diameter vessels in the cat mesentery. The experiments also show that maximally dilated 1A to 4A vessels in the microcirculation closely satisfy the condition Q(flow)/(2a)3 = constant, which is consistent with the hypothesis that there is an adaptive regulation of vessel diameter which keeps the wall shear stress nearly constant during temporal changes in flow.

Abdominal Muscles↗
PubMedDate not supplied

Electrical signal transmission and gap junction regulation in a bone cell network: a cable model for an osteon.

A cable model is formulated to estimate the spatial distribution of intracellular electric potential and current, from the cement line to the lumen of an osteon, as the frequency of the loading and the conductance of the gap junction are altered. The model predicts that the characteristic diffusion time for the spread of current along the membrane of the osteocytic processes, 0.03 sec, is nearly the same as the predicted pore pressure relaxation time in Zeng et al. (Annals of Biomedical Engineering. 1994) for the draining of the bone fluid into the osteonal canal. This approximate equality of characteristic times causes the cable to behave as a high-pass, low-pass filter cascade with a maximum in the spectral response for the intracellular potential at approximately 30 Hz. This behavior could be related to the experiments of Rubin and McLeod (Osteoporosis, Academic Press, 1996) which show that live bone appears to be selectively responsive to mechanical loading in a specific frequency range (15-30 Hz) for several species.

Action Potentials↗
PubMedDate not supplied

A model for interpreting the tracer labeling of interendothelial clefts.

We extended the model describing the low molecular weight electron dense tracer wake in the interendothelial cleft and surrounding tissue to describe the time-dependent transport of intermediate size solutes of 1.0-3.5 nm radius by convection and diffusion in an interendothelial cleft containing a fiber matrix. This model provides a quantitative basis on which to reinterpret electron microscopic studies of the distribution of tracers such as horseradish peroxidase (HRP; molecular weight = 40,000; Stokes radius = 3.0 nm) along the interendothelial cell cleft from the lumen to the tissue. For example, we show that, in contrast to our results with low molecular weight tracers, the wake of large molecular weight tracers on the abluminal side of the junctional strand is not likely to be detected, because the concentration of the tracer is predicted to be very low in most experiments. Thus the lack of a tracer such as HRP on the abluminal side of the junctional strand and in the tissue is not as strong evidence against the presence of a cleft pathway as suggested previously. The model does provide the basis for the design of experiments to locate both the principal molecular sieve and breaks in the junctional strand from the standing gradient on the luminal side of the junctional strand. An important experimental variable is the pressure in the vessel lumen which can be varied between 0 and 30 cm H2O to change the contributions of diffusive and convective transport to transcapillary exchange through he interendothelial cleft. This approach will also allow the testing of models for transcapillary pathways for large molecules by measuring the distribution of fluorescent traces across the microvessel wall and in the tissue surrounding the microvessel using confocal microscopy.

Algorithms↗
PubMedDate not supplied

Microvascular thermal equilibration in rat cremaster muscle.

A new experimental approach was developed to obtain the first direct measurements of the axial countercurrent thermal equilibration in a microvascular tissue preparation using high resolution infrared thermography. Detailed surface temperature measurements were obtained for an exteriorized rat cremaster muscle in which pharmacological vasoactive agents were used to change the local blood flow Peclet number from 1 to 14 in the feeding artery. Under normal conditions, only the 1A arteries (> 70 microns diameter) showed thermal nonequilibration with the surrounding tissue. The theoretical model developed by Zhu and Weinbaum (28) for a two-dimensional tissue preparation with arbitrarily embedded countercurrent vessels was modified to include axial conduction and the presence of the supporting glass slide. This modified model was used to interpret the experimental results and to relate the surface temperature profiles to the bulk temperature profiles in the countercurrent artery and vein and the local average tissue temperature in the cross-sectional plane. Surface temperature profiles transverse to the vessel axis are shown to depend significantly on the tissue inlet temperature. The eigenfunction for the axial thermal equilibration depends primarily on the blood flow Peclet number and the environmental convective coefficient. The theoretical results predict that when rho(ar)*Pe is less than 1 mm (the range in our experiments), axial conduction is the dominant mode of axial thermal equilibration. For 1 < rho(ar)*PE < 3 mm, countercurrent blood flow becomes comparable to axial conduction, whereas, when rho(ar)*Pe > 3 mm, countercurrent blood flow is the dominant mode of axial thermal equilibration. Therefore, for rho(ar)*Pe > 3 mm the axial equilibration length is proportional to the blood flow Peclet number, as predicted previously by Zhu and Weinbaum in a study in which axial conduction was neglected. It also is shown that the axial decay of the tissue temperature at low perfusion rates can be described by a simple one-dimensional Weinbaum-Jiji equation with a newly derived conduction shape factor.

Abdominal Muscles↗
PubMedDate not supplied

Electrical signal transmission in a bone cell network: the influence of a discrete gap junction.

A refined electrical cable model is formulated to investigate the role of a discrete gap junction in the intracellular transmission of electrical signals in an electrically coupled system of osteocytes and osteoblasts in an osteon. The model also examines the influence of the ratio q between the membrane's electrical time constant and the characteristic time of pore fluid pressure, the circular, cylindrical geometry of the osteon, and key simplifying assumptions in our earlier continuous cable model (see Zhang, D., S. C. Cowin, and S. Weinbaum. Electrical signal transmission and gap junction regulation in a bone cell network: A cable model for an osteon. Ann. Biomed. Eng. 25:379-396, 1997). Using this refined model, it is shown that (1) the intracellular potential amplitude at the osteoblastic end of the osteonal cable retains the character of a combination of a low-pass and a high-pass filter as the corner frequency varies in the physiological range; (2) the presence of a discrete gap junction near a resting osteoblast can lead to significant modulation of the intracellular potential and current in the osteoblast for measured values of the gap junction coupling strength; and (3) the circular, cylindrical geometry of the osteon is well simulated by the beam analogy used in Zhang et al.

Animals↗