Perialveolar interstitial resistance and compliance in isolated rat lung

We have developed a method to characterize fluid transport through the perialveolar interstitium using micropuncture techniques. In 10 experiments we established isolated perfused rat lung preparations. The lungs were initially isogravimetric at 10 cmH2O arterial pressure, 2 cmH2O venous pressure, and 5 cmH2O alveolar pressure. Perialveolar interstitial pressure was determined by micropuncture at alveolar junctions by use of the servo-null technique. Simultaneously a second micropipette was placed in an alveolar junction 20-40 microns away, and a bolus of albumin solution (3.5 g/100 ml) was injected. The resulting pressure transient was recorded for injection durations of 1 and 4 s in nonedematous lungs. The measurements were repeated after gross edema formation induced by elevated perfusion pressure. We model the interstitium as a homogeneous linearly poroelastic material and assume the initial pressure distribution due to the injection to be Gaussian. The pressure decay is inversely proportional to time, with time constant T, where T is a measure of the ratio of interstitial tissue stiffness to interstitial resistance to fluid flow. A linear regression was performed on the reciprocal of the pressure for the decaying portion of the transients to determine T. Comparing pressure transients in nonedematous and edematous lungs, we found that T was 4.0 +/- 1.4 and 1.4 +/- 0.6 s, respectively. We have shown that fluid transport through the pulmonary interstitium on a local level is sensitive to changes in interstitial stiffness and resistance. These results are consistent with the decreased stiffness and resistance in the perialveolar interstitium that accompany increased hydration.     

Gas dispersion in volume-cycled tube flow. I. Theory.

A mathematical theory is derived for the dispersion of a contaminant bolus introduced into a fully developed volume-cycled oscillatory pipe flow. The convection-diffusion equation is solved for a tracer gas bolus by expressing the local concentration field as a series expansion of derivatives of the area-averaged concentration. The local, as well as the area-averaged, concentration is determined for a uniform initial slug or Gaussian bolus. The effect of various flow parameters such as Womersley parameter, Schmidt number, and tidal volume is investigated. The overall dispersion is characterized by a time-averaged effective diffusion coefficient, which for long duration coincides with previous dispersion theories based on a constant linear axial concentration profile. The effective diffusion coefficient can be determined from the local time history of concentration, independent of the spatial location or the initial tracer bolus. Furthermore the local peaks of the concentration-time curve follow a decaying curve dictated by the time-averaged effective diffusion coefficient. Thus the theory is directly applicable for dispersion measurements in oscillatory tube flows, a basis for the pulmonary airways application, as shown by Gaver et al. (J. Appl. Physiol. 72: 321-331, 1992).     

Steady-state pleural fluid flow and pressure and the effects of lung buoyancy

Both theoretical and experimental studies of pleural fluid dynamics and lung buoyancy during steady-state, apneic conditions are presented. The theory shows that steady-state, top-to-bottom pleural-liquid flow creates a pressure distribution that opposes lung buoyancy. These two forces may balance, permitting dynamic lung floating, but when they do not, pleural-pleural contact is required. The animal experiments examine pleural-liquid pressure distributions in response to simulated reduced gravity, achieved by lung inflation with perfluorocarbon liquid as compared to air. The resulting decrease in lung buoyancy modifies the force balance in the pleural fluid, which is reflected in its vertical pressure gradient. The data and model show that the decrease in buoyancy with perfluorocarbon inflation causes the vertical pressure gradient to approach hydrostatic. In the microgravity analogue, the pleural pressures would be toward a more uniform distribution, consistent with ventilation studies during space flight. The pleural liquid turnover predicted by the model is computed and found to be comparable to experimental values from the literature. The model provides the flow field, which can be used to develop a full transport theory for molecular and cellular constituents that are found in pleural fluid.     

Pulsatile blood flow and oxygen transport past a circular cylinder

The fundamental study of blood flow past a circular cylinder filled with an oxygen source is investigated as a building block for an artificial lung. The Casson constitutive equation is used to describe the shear-thinning and yield stress properties of blood. The presence of hemoglobin is also considered. Far from the cylinder, a pulsatile blood flow in the x direction is prescribed, represented by a time periodic (sinusoidal) component superimposed on a steady velocity. The dimensionless parameters of interest for the characterization of the flow and transport are the steady Reynolds number (Re), Womersley parameter (alpha), pulsation amplitude (A), and the Schmidt number (Sc). The Hill equation is used to describe the saturation curve of hemoglobin with oxygen. Two different feed-gas mixtures were considered: pure O(2) and air. The flow and concentration fields were computed for Re=5, 10, and 40, 0< or =A< or =0.75, alpha=0.25, 0.4, and Schmidt number, Sc=1000. The Casson fluid properties result in reduced recirculations (when present) downstream of the cylinder as compared to a Newtonian fluid. These vortices oscillate in size and strength as A and alpha are varied. Hemoglobin enhances mass transport and is especially important for an air feed which is dominated by oxyhemoglobin dispersion near the cylinder. For a pure O(2) feed, oxygen transport in the plasma dominates near the cylinder. Maximum oxygen transport is achieved by operating near steady flow (small A) for both feed-gas mixtures. The time averaged Sherwood number, Sh, is found to be largely influenced by the steady Reynolds number, increasing as Re increases and decreasing with A. Little change is observed with varying alpha for the ranges investigated. The effect of pulsatility on Sh is greater at larger Re. Increasing Re aids transport, but yields a higher cylinder drag force and shear stresses on the cylinder surface which are potentially undesirable.     

Pulsatile flow and mass transport over an array of cylinders: gas transfer in a cardiac-driven artificial lung

The pulsatile flow and gas transport of a Newtonian passive fluid across an array of cylindrical microfibers are numerically investigated. It is related to an implantable, artificial lung where the blood flow is driven by the right heart. The fibers are modeled as either squared or staggered arrays. The pulsatile flow inputs considered in this study are a steady flow with a sinusoidal perturbation and a cardiac flow. The aims of this study are twofold: identifying favorable array geometry/spacing and system conditions that enhance gas transport; and providing pressure drop data that indicate the degree of flow resistance or the demand on the right heart in driving the flow through the fiber bundle. The results show that pulsatile flow improves the gas transfer to the fluid compared to steady flow. The degree of enhancement is found to be significant when the oscillation frequency is large, when the void fraction of the fiber bundle is decreased, and when the Reynolds number is increased; the use of a cardiac flow input can also improve gas transfer. In terms of array geometry, the staggered array gives both a better gas transfer per fiber (for relatively large void fraction) and a smaller pressure drop (for all cases). For most cases shown, an increase in gas transfer is accompanied by a higher pressure drop required to power the flow through the device.     

Particle capture into the lung made simple?

Understanding the impact distribution of particles entering the human respiratory system is of primary importance as it concerns not only atmospheric pollutants or dusts of various kinds but also the efficiency of aerosol therapy and drug delivery. To model this process, current approaches consist of increasingly complex computations of the aerodynamics and particle capture phenomena, performed in geometries trying to mimic lungs in a more and more realistic manner for as many airway generations as possible. Their capture results from the complex interplay between the details of the aerodynamic streamlines and the particle drag mechanics in the resulting flow. In contrast, the present work proposes a major simplification valid for most airway generations at quiet breathing. Within this context, focusing on particle escape rather than capture reveals a simpler structure in the entire process. When gravity can be neglected, we show by computing the escape rates in various model geometries that, although still complicated, the escape process can be depicted as a multiplicative escape cascade in which each elementary step is associated with a single bifurcation. As a net result, understanding of the particle capture may not require computing particle deposition in the entire lung structure but can be abbreviated in some regions using our simpler approach of successive computations in single realistic bifurcations. Introducing gravity back into our model, we show that this multiplicative model can still be successfully applied on up to nine generations, depending on particle type and breathing conditions.     

Spectral content of forced expiratory wheezes during air, He, and SF6 breathing in normal humans.

The effect of gas density on the spectral content of forced expiratory wheezes was studied in the search for additional information on the mechanism of generation of respiratory wheezes. Five normal adults performed forced vital capacity maneuvers through four or five orifice resistors (0.4-1.92 cm ID) after breathing air, 80% He-20% O2, or 80% SF6-20% O2. Tracheal lung sounds, flow, volume, and airway opening (Pao) and esophageal (Pes) pressures were measured during duplicate runs for each orifice and gas. Wheezes were detected in running spectra of lung sounds by use of a frequency domain peak detection algorithm. The wheeze spectrograms were presented along side expiratory flow rate and transpulmonary pressure (Ptp = Pao - Pes) as function of volume. The frequencies and patterns of wheeze spectrograms were evaluated for gas density effects. We found that air, He, and SF6 had similar wheeze spectrograms. Both wheeze frequency and patterns (as function of volume) did not exhibit consistent changes with gas density. Speech tone, however, was substantially affected in the usual pattern. These observations support the hypothesis that airway wall vibratory motion, rather than gas phase oscillations, is the source of acoustic energy of wheezes.     

Pulsatile blood flow and gas exchange across a cylindrical fiber array

The pulsatile blood flow and gas transport of oxygen and carbon dioxide through a cylindrical array of microfibers are numerically simulated. Blood is modeled as a homogeneous Casson fluid, and hemoglobin molecules in blood are assumed to be in local equilibrium with oxygen and carbon dioxide. It is shown that flow pulsatility enhances gas transport and the amount of gas exchange is sensitive to the blood flow field across the fibers. The steady Sherwood number dependence on Reynolds number was shown to have a linear relation consistent with experimental findings. For most cases, an enhancement in gas transport is accompanied with an increase in flow resistance. Maximum local shear stress is provided as a possible indicator of thrombosis, and the computed shear stress is shown to be below the threshold value for thrombosis formation for all cases evaluated.     

Effects of inertia and gravity on liquid plug splitting at a bifurcation

Liquid plugs may form in pulmonary airways during the process of liquid instillation or removal in many clinical treatments. During inspiration the plug may split at airway bifurcations and lead to a nonuniform final liquid distribution, which can adversely affect treatment outcomes. In this paper, a combination of bench top experimental and theoretical studies is presented to study the effects of inertia and gravity on plug splitting in an airway bifurcation model to simulate the liquid distributions in large airways. The splitting ratio, Rs, is defined as the ratio of the plug volume entering the upper (gravitationally opposed) daughter tube to the lower (gravitationally favored) one. Rs is measured as a function of parent tube Reynolds number, Rep; gravitational orientations for roll angle, phi, and pitch angle, gamma; parent plug length LP; and the presence of pre-existing plug blockages in downstream daughter tubes. Results show that increasing Rep causes more homogeneous splitting. A critical Reynolds number Rec is found to exist so that when Rep < or = Rec, Rs = 0, i.e., no liquid enters the upper daughter tube. Rec increases while Rs decreases with increasing the gravitational effect, i.e., increasing phi and gamma. When a blockage exists in the lower daughter, Rec is only found at phi = 60 deg in the range of Rep studied, and the resulting total mass ratio can be as high as 6, which also asymptotes to a finite value for different phi as Rep increases. Inertia is further demonstrated to cause more homogeneous plug splitting from a comparison study of Rs versus Cap (another characteristic speed) for three liquids: water, glycerin, and LB-400X. A theoretical model based on entrance flow for the plug in the daughters is developed and predicts Rs versus Rep. The frictional pressure drop, as a part of the total pressure drop, is estimated by two fitting parameters and shows a linear relationship with Rep. The theory provides a good prediction on liquid plug splitting and well simulates the liquid distributions in the large airways of human lungs.