Search PubMed⌕ Search

Biomedical subjects

W J Federspiel

Publications and source records attributed to W J Federspiel.

At least 19 recordsLinked to original sources

Validation of a model for flow-dependent carbon dioxide exchange in artificial lungs.

The exchange rate of CO2 in artificial lungs depends on the sweep gas flow rate. Control of the amount of CO2 removed by an artificial lung requires quantitative knowledge of the flow dependence. A simple model of the dependence of CO2 exchange on sweep gas flow rate in artificial lungs has been previously presented (1). For a given partial pressure of CO2 in the blood phase, sweep gas flow rate, and CO2 exchange rate, the model indicates how close the CO2 exchange rate is to the maximum level attainable by the artificial lung. The focus of this study was to validate the model experimentally by testing 2 commercial artificial lungs in an in vitro test loop. The CO2 exchange rate for each artificial lung was measured over a range of sweep gas flow rates. Linear regression was used to fit the data to the model and estimate the maximum possible CO2 exchange rate and the average water-side PCO2 (PCO2w). The difference between the measured and regressed values of PCO2w was used as an indicator of the ability of the model to quantitatively predict the dependence of CO2 exchange on gas flow rate. This difference was less than 5% for each experiment, indicating that the model can be used to guide control of CO2 exchange rates in artificial lungs.

Algorithms↗

Experimental evaluation of a model for oxygen exchange in a pulsating intravascular artificial lung.

Intravascular oxygenation and carbon dioxide removal remains a potentially attractive means for respiratory support in patients with acute or chronic respiratory failure. Our group has been developing an intravascular hollow fiber artificial lung that uses a pulsating balloon located within the fiber bundle to augment gas transfer. We previously reported on a simple compartmental model for simulating O2 exchange in pulsating intravascular artificial lungs. In this study we evaluate the O2 exchange model with gas exchange and PO2 measurements performed on an idealized intravascular artificial lung (IIVAL) tested in a water perfusion loop. The IIVAL has well-defined bundle geometry and can be operated in balloon pulsation mode, or a steady perfusion mode for determining the mass transfer correlation required by the model. The O2 exchange rates and compartmental O2 tensions measured with balloon pulsation in the IIVAL are within 10% of model predictions for flow and pulsation conditions relevant to intravascular oxygenation. The experiments confirmed that a significant buildup of PO2 occurs within the fiber bundle, which reduces the O2 exchange rate. The agreement between experiments and predictions suggests that the model captures the cardinal processes dictating gas transfer in pulsating intravascular artificial lungs.

Humans↗

Effect of intraluminal thrombus thickness and bulge diameter on the oxygen diffusion in abdominal aortic aneurysm.

The intraluminal thrombus (ILT) commonly found within abdominal aortic aneurysm (AAA) may serve as a barrier to oxygen diffusion from the lumen to the inner layers of the aortic wall. The purpose of this work was to address this hypothesis and to assess the effects of AAA bulge diameter (dAAA) and ILT thickness (delta) on the oxygen flow. A hypothetical, three-dimensional, axisymmetric model of AAA containing ILT was created for computational analysis. Commercial software was utilized to estimate the volume flow of O2 per cell, which resulted in zero oxygen tension at the AAA wall. Solutions were generated by holding one of the two parameters fixed while varying the other. The supply of O2 to the AAA wall increases slightly and linearly with dAAA for a fixed delta. This slight increase is due to the enlarged area through which diffusion of O2 may take place. The supply of O2 was found to decrease quickly with increasing delta for a fixed dAAA due to the increased resistance to O2 transport by the ILT layer. The presence of even a thin, 3 mm ILT layer causes a diminished O2 supply (less than 4 x 10(-10) mumol/min/cell). Normally functioning smooth muscle cells require a supply of 21 x 10(-10) mumol/min/cell. Thus, our analysis serves to support our hypothesis that the presence of ILT alters the normal pattern of O2 supply to the AAA wall. This may lead to hypoxic cell dysfunction in the AAA wall, which may further lead to wall weakening and increased potential for rupture.

Animals↗

Sweep gas flowrate and CO2 exchange in artificial lungs.

A simple analysis and graphic result are presented for characterizing the dependence of CO2 exchange on the sweep gas (ventilating gas) flowrate in artificial lungs. The analysis requires no knowledge of the device-specific mass transfer characteristics of an artificial lung, nor does it require detailed mathematical modeling or computer simulation. Rather, it uses appropriate normalization to establish generic features of the gas flow dependency of CO2 exchange that are applicable to all artificial lung devices. Principal results are that the transition from relatively gas flow-sensitive to gas flow-insensitive CO2 exchange occurs at sweep gas flowrates of approximately 40-60 times the CO2 exchange rate. Achieving a CO2 exchange rate within 85% of maximal (for a given oxygenator and blood-side conditions) requires a sweep gas flowrate of no less than approximately 50 times the nominal CO2 exchange rate. When the sweep gas flowrate is less than 20 times the CO2 exchange rate, CO2 exchange is highly gas flow dependent and less than one-half the maximal possible rate.

Artificial Organs↗

Model experiments on measuring flow in microvessels using tracers.

Most techniques for measuring plasma or red cell flow velocity within microvessels rely on determining the transit time of a tracer to transverse the distance between two monitoring sites within a vessel. In principle, proper transit time determinations require flow-weighted sampling of the tracer at monitoring sites. In practical application of the tracer technique, however, trace sampling at monitoring sites is not flow-weighted but is area-weighted, and hence elapsed transient time can only be estimated from tracer data. We previously showed theoretically (Microvasc. Res. 40, 394-411, 1990) that the flow velocity determined under these conditions can differ appreciably from the actual mean flow velocity of the carrier fluid within the microvessel. Nevertheless, trace mean flow velocity does approach that of the fluid when tracer velocity is measured past a finite distance from the microvessel entrance. In this study, we examined the tracer measurement of flow experimentally using a physical model. We perfused single glass microvessels and simple fabricated microvessel networks with distilled water at physiological flow rates. Mean tracer velocity (Vd) was determined at several axial locations within the microvessels using injected Evans blue dye. At each location Vd was determined in a manner consistent with usual application of the tracer flow measurement technique. Actual mean flow velocity (Va) was determined from the measured effluent flow rates discharged from each microvessel. Our experimental results confirm the existence of an appreciable velocity measurement error (VME) associated with the tracer technique. The VME behavior was consistent with our original theoretical analysis. Vd was significantly smaller than Va within a finite length of vessel near the entrance, but approached and became equal to Va past this length. Furthermore, even under conditions where the VME was negligible at the end of a parent microvessel, a new and appreciable VME arose within the connecting downstream daughter microvessels. These results underscore that tracer mean flow velocity as obtained in normal implementation of the tracer technique can differ from that for the fluid itself within a microvascular network.

Blood Flow Velocity↗

Morphometric model for pulmonary diffusing capacity. I. Membrane diffusing capacity.

The pulmonary diffusing capacity is related to the quantitative design characteristics of the pulmonary gas exchanger. The current model for estimating DLO2 from morphometric data breaks the diffusion path for O2 into four steps, three of which represent the membrane part of DLO2. A critique of this model on the basis of newer evidence leads to a modification of the model where the path from the alveolar surface to the erythrocyte membrane is considered as a single step. The structural determinant of this model for DMO2 is the ratio of effective diffusion surface to effective total barrier thickness. The effective surface is formulated as a fraction of the alveolar surface area, the most robust measure of lung design, whereas the effective barrier thickness is the harmonic mean distance--or mean proximity--between alveolar surface and erythrocyte surface. The methods for obtaining the morphometric measurements are discussed. The results show that the new morphometric estimates of DMO2 are 33% lower than those obtained with the old model, resulting in a reduction of the estimates of DLO2 by 10-20%.

Animals↗

Influence of bifurcations on forced oscillations in an airway model.

Forced oscillations is a technique to determine respiratory input impedance from small amplitude sinusoidal pressure excursions introduced at the airway opening. Models used to predict respiratory input impedance typically ignore the direct effect of bifurcations on the flow, and treat airway branches as individual straight tubes placed appropriately in parallel and series. The flow within the individual tubes is assumed equivalent to that which would occur in infinitely long tubes. In this study we examined the influence of bifurcations on impedance for conditions of the forced oscillatory technique. We measured input impedance using forced oscillations in straight tubes and in an anatomically-relevant, four generation physical model of a human airway network. The input impedance measured experimentally compared well to that obtained theoretically using model predictions. The predictive scheme was based on appropriate parallel and series combinations of theoretically computed individual tube impedances, which were computed from solutions to oscillatory flow of a compressible gas in an infinitely long rigid tube. The agreement between experimental measurements and predictions indicates that bifurcations play a relatively minor direct role on the flow impedance for conditions of the forced oscillations technique. These results are explained in terms of the small tidal volumes used, whereby the axial distance traveled by a fluid particle during an oscillation cycle is appreciably smaller than branch segment lengths. Accordingly, only a small fraction of fluid particles travel through the bifurcation region, and the remainder experience an environment approaching flow in an infinite straight tube. The relevance of the study to the prediction of impedances in the human lung during forced oscillations is discussed.

Airway Resistance↗

Use of tracers to measure flow within single microvessels.

Most techniques for making quantitative measurements of flow within single microvessels rely on tracers which are injected upstream of the microvessel and monitored noninvasively (e.g., optical densitometry) at selected sites along the microvessel. This study examines theoretically the measurement of average flow velocity (v) within individual microvessels from tracer flow data at monitoring sites. Starting with a fundamental convection-diffusion equation, the theory considers tracers which can distribute across both plasma and red cell phases. An integral analysis indicates that v = delta zeta/delta tau, where delta zeta is the distance between monitoring sites, and delta tau is the tracer transit or "residence" time needed to traverse that distance. The residence time which arises explicitly requires measurement of the flow-weighted average tracer concentration at each monitoring site. Because noninvasive tracer measurements provide indices of the unweighted average tracer concentration, a velocity measurement error, delta(zeta), arises, delta(zeta) is quantified in relation to the axial location of the measurement site, the velocity profile, the tracer Peclet number, and the radial distribution of tracer at the vessel inlet. delta(zeta) does not vanish when tracer enters a microvessel with a radially uniform concentration profile, but does vanish past a critical distance, Lc, from the microvessel entrance. The critical distance can be estimated using Lc/d = 0.05(vd)/D (d. vessel diameter; v, average flow velocity; D, tracer diffusivity). Accordingly, tracer data can be used to quantify flow velocity within a microvessel provided the microvessel length allows for monitoring tracer flow beyond the estimated Lc value. This study serves as a necessary precursor to analyses of plasma-phase tracers used to measure microvascular plasma flow.

Blood Flow Velocity↗

Pulmonary diffusing capacity: implications of two-phase blood flow in capillaries.

The classical view of oxygen (O2) uptake in pulmonary capillaries assumes implicitly that capillary blood can be regarded as a continuous homogeneous hemoglobin solution. In this study a theoretical model was used to examine the role played by the particulate (two-phase) nature of blood on pulmonary oxygen exchange. Red cells were modelled as discrete hemoglobin (Hb) containing spheres flowing in single file suspension through a cylindrical capillary surrounded by a uniform annulus of alveolar tissue. The model accounted for the free diffusion of O2 from alveolar air space through tissue and plasma, free and Hb facilitated diffusion of O2 inside red cells, and the intracellular kinetics of O2-Hb binding. Oxygen uptake was driven by a specified O2 tension at the alveolar surface. The computed pulmonary diffusing capacity (DLO2) decreased with increasing spacing (Ls) between red cells. The reduction in DLO2 with increasing Ls was marshalled more by a reduction in membrane diffusing capacity (DMO2), than by the reduction in erythrocyte diffusing capacity (DeO2). The dependence of DMO2 on cell spacing stemmed from the manner in which O2 flowed across the alveolar surface into the discrete sinks (red cells) within the capillaries. The degree to which Ls influenced DMO2 was dependent on tissue and plasma layer thickness relative to red cell dimensions. The results indicate that the functional area of the alveolo-capillary membrane for O2 exchange depends on the red cell content of capillaries. Thus, DMO2 is not dictated solely by the morphology of the exchange apparatus (and physical parameters), but has functional determinants as well.

Capillaries↗

Axial dispersion in respiratory bronchioles and alveolar ducts.

The mixing of gases in the pulmonary acinus was characterized by analyzing axial gas dispersion during steady flow in models of respiratory bronchioles and alveolar ducts. An analysis (method of moments) developed for addressing dispersion in porous media was used to derive an integral expression for the axial dispersion coefficient (D*). Evaluation of D* required solving the Navier-Stokes equations for the flow field and a convection-diffusion type equation arising from the analysis. D* was strongly dependent on alveolar volume per central duct volume, the aperture size through which the alveoli communicate with the central duct, and the Péclet number (Pe). At smaller Pe (flow rate) D* was substantially smaller than the molecular diffusion coefficient, whereas at larger Pe (flow rate) D* was much greater than the Taylor-Aris result for flow-enhanced dispersion in straight tubes. Also, flow-enhanced dispersion became appreciable at smaller Pe than indicated by the Taylor-Aris result. These behaviors transcend both the lower and upper limits established previously for gas mixing in the pulmonary acinus.

Animals↗

A theoretical analysis of the effect of the particulate nature of blood on oxygen release in capillaries.

A theoretical model is developed to investigate the role played by the particulate (two-phase) nature of blood on oxygen (O2) release in capillary-size vessels. Red cells flowing in single-file suspension through capillaries are modelled as evenly spaced, hemoglobin (Hb)-containing circular particles in a rectangular channel (two-dimensional case) or axisymmetric spheres in a circular tube (three-dimensional case). The model includes the free and Hb-facilitated transport of O2 and Hb-O2 kinetics inside the particles, diffusion of free O2 in the suspending phase, and a specified O2 tension at the capillary wall that drives the release of O2 from the particles as they traverse the capillary. The results are expressed in the form of a capillary mass transfer coefficient, an inverse resistance, that relates the spatial average flux of O2 out of the capillary to a driving force for O2 release. The results indicate that this coefficient depends significantly on particle spacing and clearance (channel size relative to particle size) but not significantly on the O2 tension at the capillary wall nor the eccentricity of the particles in the channel. It is also found that the capillary mass transfer coefficient can be several times smaller (more resistance) than that for a continuous Hb solution releasing O2. As a physiological application of the coefficients obtained, they are combined with a Krogh-type model for tissue, and the resulting analysis suggests that the fraction of total O2 transport resistance that resides inside the capillary is influenced significantly by the discrete nature of blood and can account for 30 to 70% of the total resistance to O2 transport from blood to tissue.

Biological Transport, Active↗

A model study of intracellular oxygen gradients in a myoglobin-containing skeletal muscle fiber.

A theoretical two-dimensional model is used to investigate oxygen gradients in a red skeletal muscle fiber. The model describes the steady state, free and myoglobin-facilitated diffusion of oxygen into a respiring cylindrical muscle fiber cross section. The oxygen tension at the sarcolemma is assumed to vary along the sarcolemma as an approximation to the discrete capillary oxygen supply around the fiber. Maximal oxygen gradients are studied by considering parameters relevant to a maximally-respiring red muscle fiber. The model predicts that angular variations in the oxygen tension imposed at the sarcolemma due to the discrete capillary sources do not penetrate deeply into the fiber over a range of physiological values for myoglobin concentration, diffusion coefficients, number of surrounding capillaries, and oxygen tension level at the sarcolemma. Also, the oxygen tension in the core of the fiber is determined by the average oxygen tension at the sarcolemma. The drop in oxygen tension from fiber periphery to core, however, does depend significantly on the myoglobin concentration, the oxygen tension level at the sarcolemma, and the oxygen and myoglobin diffusivities. This dependence is summarized by calculating the minimum average sarcolemmal oxygen tension for maximal respiration without the development of an intracellular anoxic region. For a myoglobin-rich muscle fiber (0.5 mM myoglobin), the model predicts that maximal oxygen consumption can proceed with a relatively flat (less than 5 mm Hg) oxygen tension drop from fiber periphery to core over a large range for diffusion coefficients.

Animals↗

Oxygen delivery from red cells.

This paper deals with the theoretical analysis of the unloading of oxygen from a red cell. A scale analysis of the governing transport equations shows that the solutions have a boundary layer structure near the red-cell membrane. The boundary layer is a region of chemical nonequilibrium, and it owes its existence to the fact that the kinetic time scales are shorter than the diffusion time scales in the red cell. The presence of the boundary layer allows an analytical solution to be obtained by the method of matched asymptotic expansions. A very useful result from the analysis is a simple, lumped-parameter description of the oxygen delivery from a red cell. The accuracy of the lumped-parameter description has been verified by comparing its predictions with results obtained by numerical integration of the full equations for a one-dimensional slab. As an application, we calculate minimum oxygen unloading times for red cells.

Biological Transport, Active↗