Distensibility and pressure-flow relationship of the pulmonary circulation. II. Multibranched model

The contribution of distensibility and recruitment to the distinctive behavior of the pulmonary circulation is not known. To examine this question we developed a multibranched model in which an arterial vascular bed bifurcates sequentially up to 8 parallel channels that converge and reunite at the venous side to end in the left atrium. Eight resistors representing the capillary bed separate the arterial and venous beds. The elastic behavior of capillaries and extra-alveolar vessels was modeled after Fung and Sobin (Circ. Res. 30: 451-490, 1972) and Smith and Mitzner (J. Appl. Physiol. 48: 450-467, 1980), respectively. Forces acting on each component are modified and calculated individually, thus enabling the user to explore the effects of parallel and longitudinal heterogeneities in applied forces (e.g., gravity, vasomotor tone). Model predictions indicate that the contribution of distensibility to nonlinearities in the pressure-flow (P-F) and atrial-pulmonary arterial pressure (Pla-Ppa) relationships is substantial, whereas gravity-related recruitment contributes very little to these relationships. In addition, Pla-Ppa relationships, obtained at a constant flow, have no discriminating ability in identifying the presence or absence of a waterfall along the circulation. The P-F relationship is routinely shifted in a parallel fashion, within the physiological flow range, whenever extra forces (e.g., lung volume, tone) are applied uniformly at one or more branching levels, regardless of whether a waterfall is created. For a given applied force, the magnitude of parallel shift varies with proportion of the circulation subjected to the added force and with Pla.     

Prediction of maximum expiratory flow rate from area-transmural pressure curve of compressed airway.

The site of greatest airway deformation in dog lungs was located during maximum expiratory flow by use of tantalum bronchography, fiberoptic bronchoscopy, and airway pressure measurements. A series of area vs. transmural pressure curves for each of these segments of the airway was produced after stepwise changes in transmural pressure. Measurements of area were made using cinephotography to elucidate the effect of time on airway compliance. The maximum flow rate was calculated using the t = 0.1 s compliance curve of the airway. An equation was derived so that maximum flow (V) could be calculated from the area (A) and transmural pressure (Ptm) of the flow-limiting segment. This equation, V = K-A square root of Ptm, implied that if V were constant then A must vary as Ptm-1/2. It was demonstrated that the area-transmural pressure curve of the flow-limiting segment showed this relationship between A and Ptm and that the flow calculated from this equation and the data from the A-Ptm curve gave flows identical to those measured during maximum expiration. The phenomena of effort-independent flow and negative effort dependence are also explained in terms of the area-transmural pressure curve of the flow-limiting segment.     

Modeling expiratory flow from excised tracheal tube laws.

Flow limitation during forced exhalation and gas trapping during high-frequency ventilation are affected by upstream viscous losses and by the relationship between transmural pressure (Ptm) and cross-sectional area (A(tr)) of the airways, i.e., tube law (TL). Our objective was to test the validity of a simple lumped-parameter model of expiratory flow limitation, including the measured TL, static pressure recovery, and upstream viscous losses. To accomplish this objective, we assessed the TLs of various excised animal tracheae in controlled conditions of quasi-static (no flow) and steady forced expiratory flow. A(tr) was measured from digitized images of inner tracheal walls delineated by transillumination at an axial location defining the minimal area during forced expiratory flow. Tracheal TLs followed closely the exponential form proposed by Shapiro (A. H. Shapiro. J. Biomech. Eng. 99: 126-147, 1977) for elastic tubes: Ptm = K(p) [(A(tr)/A(tr0))(-n) - 1], where A(tr0) is A(tr) at Ptm = 0 and K(p) is a parametric factor related to the stiffness of the tube wall. Using these TLs, we found that the simple model of expiratory flow limitation described well the experimental data. Independent of upstream resistance, all tracheae with an exponent n < 2 experienced flow limitation, whereas a trachea with n > 2 did not. Upstream viscous losses, as expected, reduced maximal expiratory flow. The TL measured under steady-flow conditions was stiffer than that measured under expiratory no-flow conditions, only if a significant static pressure recovery from the choke point to atmosphere was assumed in the measurement.     

Sensitivity and specificity of the computational model for maximal expiratory flow

The computational model for forced expiratory flow from human lungs of Lambert and associates (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 52: 44-56, 1982) was used to investigate the sensitivity of maximal expiratory flow to lung properties. It was found that maximal flow is very sensitive to recoil pressure and airway areas but not very sensitive to lung volume, airway compliance, and airway length. Linear programming was used to show that a given air flow-pressure curves was compatible with a fairly wide range of airway properties. Additional data for maximal flow with a He-O2 mixture narrowed the range somewhat. It was shown that the flow-pressure curve contains more information about central than peripheral airways and that information about the latter is obtainable only from flows at recoils less than 2 cmH2O. Parameter ranges compatible with individual flow-pressure curves showed differences that demonstrated that such curves give some indication of individual central airway properties.     

Effect of variable parenchymal expansion on gas mixing

Using implanted radiopaque markers, Hubmayr et al. (J. Appl. Physiol. 54: 1048-1056, 1983) and Olson et al. (J. Appl. Physiol. 57: 1710-1714, 1984) detected a variability in the volume changes of regions defined by the markers in intact and excised dog lungs, respectively. In dogs lying prone and in excised lobes, there is virtually no large-scale spatial organization of the variability. We interpret these data as evidence of an intrinsic heterogeneity of parenchymal expansion. The effect of variability of parenchymal expansion on gas mixing is calculated. From a statistical model, we infer that the variability of volume changes observed by Olson et al. is a result of an underlying variability with a larger magnitude at a smaller scale and that the variability at the smaller scale is large enough to explain the inefficiency of mixing observed in single-breath oxygen tests on excised dog lobes.     

A method for analysis of pulmonary arterial and venous occlusion data.

Recently, we presented a compartmental model of the pulmonary vascular resistance (R) and compliance (C) distribution with the configuration C1R1C2R2C3 (J. Appl. Physiol. 70: 2126-2136, 1991). This model was used to interpret the pressure vs. time data obtained after the sudden occlusion of the arterial inflow (AO), venous outflow (VO), or both inflow and outflow (DO) from an isolated dog lung lobe. In the present study, we present a new approach to the data analysis in terms of this model that is relatively simple to carry out and more robust. The data used to estimate the R's and C's are the steady-state arterial [Pa(0)] and venous [Pv(0)] pressures, the flow rate (Q), the area (A2) encompassed by Pa(t) after AO and the equilibrium pressure (Pd) after DO, and the average slope (m) of the Pa(t) and Pv(t) curves after VO. The following formulas can then be used to calculate the 2 R's and 3 C's: [Pa(0) - Pv(0)]/Q = R1 + R2 = RT, R1C1 congruent to to A2/[Pa(0) - Pd], R1 congruent to [Pa(0) - Pd]/Q, Q/m = C1 + C2 + C3 = CT, and C2 = CT - (RTC1/R2).     

Effects of lung inflation on pulmonary arterial blood volume in intact dogs.

The isolated effects of alterations of lung inflation and transmural pulmonary arterial pressure (pressure difference between intravascular and pleural pressure) on pulmonary arterial blood volume (Vpa) were investigated in anesthetized intact dogs. Using transvenous phrenic nerve stimulation, changes in transmural pulmonary arterial pressure (Ptm) at a fixed transpulmonary pressure (Ptp) were produced by the Mueller maneuver, and increases in Ptp at relatively constant Ptm by a quasi-Valsalva maneuver. Also, both Ptm and Ptp were allowed to change during open airway lung inflation. Vpa was determined during these three maneuvers by multiplying pulmonary blood flow by pulmonary arterial mean transit time obtained by an ether plethysmographic method. During open airway lung inflation, mean (plus or minus SD) Ptp increased by 7.2 (plus or minus 3.7) cmH2O and Ptm by 4.3 (plus or minus 3.4) cmH2O for a mean increase in Vpa by 26.2 (plus or minus 10.7) ml. A pulmonary arterial compliance term (Delta Vpa/Delta Ptm) calculated from the Mueller maneuver was 3.9 ml/cmH2O and an interdependence term (Delta Vpa/Delta Ptp) calculated from the quasi-Valsalva maneuver was 2.5 ml/cmH2O for a 19% increase in lung volume, and 1.2 ml/cmH2O for an increase in lung volume from 19% to 35%. These findings indicate that in normal anesthetized dogs near FRC for a given change in Ptp and Ptm the latter results in a greater increase of Vpa.     

Very high pressures are required to cause stress failure of pulmonary capillaries in Thoroughbred racehorses

Birks, Eric K., Odile Mathieu-Costello, Zhenxing Fu, WalterS. Tyler, and John B. West. Very high pressures are required tocause stress failure of pulmonary capillaries in Thoroughbred racehorses. J. Appl. Physiol. 82(5):1584-1592, 1997.Thoroughbred horses develop extremely highpulmonary vascular pressures during galloping, all horses in trainingdevelop exercise-induced pulmonary hemorrhage, and we have shown thatthis is caused by stress failure of pulmonary capillaries. It is knownthat the capillary transmural pressure (Ptm) necessary for stressfailure is higher in dogs than in rabbits. The present study wasdesigned to determine this value in horses. The lungs from 15 Thoroughbred horses were perfused with autologous blood at Ptm values(midlung) of 25, 50, 75, 100 and 150 mmHg, and then perfusion fixed,and samples (dorsal and ventral, from caudal region) were examined byelectron microscopy. Few disruptions of capillary endothelium wereobserved at Ptm  75 mmHg, and 5.3 ± 2.2 and 4.3 ± 0.7 breaks/mm endothelium were found at 100 and 150 mmHg Ptm, respectively.Blood-gas barrier thickness did not change with Ptm. At low Ptm,interstitial thickness was greater than previously found in rabbits butnot in dogs. We conclude that the Ptm required to cause stress failureof pulmonary capillaries is between 75 and 100 mmHg and is greater inThoroughbred horses than in both rabbits and dogs.

     

Influence of lung volume on pulmonary microvascular pressure-volume characteristics.

The pressure-volume (P-V) characteristics of the lung microcirculation are important determinants of the pattern of pulmonary perfusion and of red and white cell transit times. Using diffuse light scattering, we measured capillary P-V loops in seven excised perfused dog lobes at four lung volumes, from functional residual capacity (FRC) to total lung capacity (TLC), over a wide range of vascular transmural pressures (Ptm). At Ptm 5 cmH(2)O, specific compliance of the microvasculature was 8.6%/cmH(2)O near FRC, decreasing to 2.7%/cmH(2)O as lung volume increased to TLC. At low lung volumes, the vasculature showed signs of strain stiffening (specific compliance fell as Ptm rose), but stiffening decreased as lung volume increased and was essentially absent at TLC. The P-V loops were smooth without sharp transitions, consistent with vascular distension as the primary mode of changes in vascular volume with changes in Ptm. Hysteresis was small (0.013) at all lung volumes, suggesting that, although surface tension may set basal capillary shape, it does not strongly affect capillary compliance.     

Model of oxygen transport and metabolism predicts effect of hyperoxia on canine muscle oxygen uptake dynamics.

Previous studies have shown that increased oxygen delivery, via increased convection or arterial oxygen content, does not speed the dynamics of oxygen uptake, Vo(2m), in dog muscle electrically stimulated at a submaximal metabolic rate. However, the dynamics of transport and metabolic processes that occur within working muscle in situ is typically unavailable in this experimental setting. To investigate factors affecting Vo(2m) dynamics at contraction onset, we combined dynamic experimental data across working muscle with a mechanistic model of oxygen transport and metabolism in muscle. The model is based on dynamic mass balances for O(2), ATP, and PCr. Model equations account for changes in cellular ATPase, oxidative phosphorylation, and creatine kinase fluxes in skeletal muscle during exercise, and cellular respiration depends on [ADP] and [O(2)]. Model simulations were conducted at different levels of arterial oxygen content and blood flow to quantify the effects of convection and diffusion of oxygen on the regulation of cellular respiration during step transitions from rest to isometric contraction in dog gastrocnemius muscle. Simulations of arteriovenous O(2) differences and (.)Vo(2m) dynamics were successfully compared with experimental data (Grassi B, Gladden LB, Samaja M, Stary CM, Hogan MC. J Appl Physiol 85: 1394-1403, 1998; and Grassi B, Gladden LB, Stary CM, Wagner PD, Hogan MC. J Appl Physiol 85: 1404-1412, 1998), thus demonstrating the validity of the model, as well as its predictive capability. The main findings of this study are: 1) the estimated dynamic response of oxygen utilization at contraction onset in muscle is faster than that of oxygen uptake; and 2) hyperoxia does not accelerate the dynamics of diffusion and consequently muscle oxygen uptake at contraction onset due to the hyperoxia-induced increase in oxygen stores. These in silico derived results cannot be obtained from experimental observations alone.     

Periodic flow at airway bifurcations. I. Development of steady pressure differences

In studies of large-amplitude periodic flows at an airway bifurcation, we found an appreciable steady-state pressure difference between the terminal units. To elucidate the fluid dynamic origins of such steady-state pressure differences, we studied single asymmetric bifurcation models with various area ratios and branching angles. The daughter ducts were identical in size and were terminated into identical elastic loads. Sinusoidal flow oscillations were applied at the parent duct so that the upstream Reynolds number ranged from 30 to 77,000 and the Womersley parameter from 2 to 30. The steady-state component (time averaged) of the pressure measured at the terminal with the smaller branching angle was found to be consistently higher than that at the other terminal. This steady-state pressure difference scaled approximately as a fixed fraction of the parent duct dynamic head. Guided by the results of flow-visualization studies, we modeled such behavior based on the temporal and spatial differences of head loss between the two branches of the bifurcation. Our results suggest that interlobar heterogeneity of mean alveolar-pressure observed in excised canine lungs during high frequency oscillation (Allen et al., J. Appl. Physiol. 62: 223-228, 1987) arises solely from fluid dynamic origins: differential head loss due to asymmetry of central airway branching structure.     

Anatomically based three-dimensional model of airways to simulate flow and particle transport using computational fluid dynamics.

We have studied gas flow and particle deposition in a realistic three-dimensional (3D) model of the bronchial tree, extending from the trachea to the segmental bronchi (7th airway generation for the most distal ones) using computational fluid dynamics. The model is based on the morphometrical data of Horsfield et al. (Horsfield K, Dart G, Olson DE, Filley GF, and Cumming G. J Appl Physiol 31: 207-217, 1971) and on bronchoscopic and computerized tomography images, which give the spatial 3D orientation of the curved ducts. It incorporates realistic angles of successive branching planes. Steady inspiratory flow varying between 50 and 500 cm(3)/s was simulated, as well as deposition of spherical aerosol particles (1-7 microm diameter, 1 g/cm(3) density). Flow simulations indicated nonfully developed flows in the branches due to their relative short lengths. Velocity flow profiles in the segmental bronchi, taken one diameter downstream of the bifurcation, were distorted compared with the flow in a simple curved tube, and wide patterns of secondary flow fields were observed. Both were due to the asymmetrical 3D configuration of the bifurcating network. Viscous pressure drop in the model was compared with results obtained by Pedley et al. (Pedley TJ, Schroter RC, and Sudlow MF. Respir Physiol 9: 387-405, 1970), which are shown to be a good first approximation. Particle deposition increased with particle size and was minimal for approximately 200 cm(3)/s inspiratory flow, but it was highly heterogeneous for branches of the same generation.     

Respiratory transfer impedances with pressure input at the mouth and chest

Two methods of measuring respiratory transfer impedance (Ztr) were compared in 14 normal subjects, from 4 to 30 Hz, 1) studying the relationship between transrespiratory pressure (Prs) and flow at the chest when varying pressure at the mouth (Ztrm) and 2) studying the relationship between Prs and flow at the mouth when varying pressure around the chest wall (Ztrw). The similarity of the two relationships was expected on the basis of a T-network model. Almost identical phase responses were obtained from the two methods. Pressure-flow ratios were slightly larger for Ztrw than for Ztrm, but differences did not exceed 2% on average in 11 of 14 subjects. When the data were analyzed with the six-coefficient model proposed by DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956), similar values were found for tissue compliance and tissue inertance but slightly different values for gaseous inertance in the airways (1.97 +/- 0.35 X 10(-2) cmH2O X l-1 X s2 for Ztrw vs. 1.73 +/- 0.26 for Ztrm; P less than 0.01). Similar results were also found for total respiratory resistance but with a slightly larger contribution of airway resistance for Ztrw (64 +/- 14 vs. 57 +/- 10%; P less than 0.05). As a practical conclusion it is recommended to measure Ztrw, which is technically much easier.     

High lung volume increases stress failure in pulmonary capillaries.

We previously showed that when pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to test whether stress failure occurred more frequently at high than at low lung volumes for the same Ptm. Lungs of anesthetized rabbits were inflated to a transpulmonary pressure of 20 cmH2O, perfused with autologous blood at 32.5 or 2.5 cmH2O Ptm, and fixed by intravascular perfusion. Samples were examined by both transmission and scanning electron microscopy. The results were compared with those of a previous study in which the lung was inflated to a transpulmonary pressure of 5 cmH2O. There was a large increase in the frequency of stress failure of the capillary walls at the higher lung volume. For example, at 32.5 cmH2O Ptm, the number of endothelial breaks per millimeter cell lining was 7.1 +/- 2.2 at the high lung volume compared with 0.7 +/- 0.4 at the low lung volume. The corresponding values for epithelium were 8.5 +/- 1.6 and 0.9 +/- 0.6. Both differences were significant (P less than 0.05). At 52.5 cmH2O Ptm, the results for endothelium were 20.7 +/- 7.6 (high volume) and 7.1 +/- 2.1 (low volume), and the corresponding results for epithelium were 32.8 +/- 11.9 and 11.4 +/- 3.7. At 32.5 cmH2O Ptm, the thickness of the blood-gas barrier was greater at the higher lung volume, consistent with the development of more interstitial edema. Ballooning of the epithelium caused by accumulation of edema fluid between the epithelial cell and its basement membrane was seen at 32.5 and 52.5 cmH2O Ptm. At high lung volume, the breaks tended to be narrower and fewer were oriented perpendicular to the axis of the pulmonary capillaries than at low lung volumes. Transmission and scanning electron microscopy measurements agreed well. Our findings provide a physiological mechanism for other studies showing increased capillary permeability at high states of lung inflation.     

Analysis of pharyngeal resistance and genioglossal EMG activity using a model of orifice flow.

A model of orifice flow has been used to analyze the relationships among pressure, flow, and genioglossal electromyographic activity in the human pharynx during inspiration. The orifice flow model permits one to assess the character of airflow (laminar or turbulent) and to estimate the cross-sectional area of the orifice from pressure and flow measurements. On the basis of other data (J. Appl. Physiol. 73: 584-590, 1992), this analysis suggests that pharyngeal airflow is turbulent. Furthermore the area of the pharynx appears to increase as flow increases, but the actual change in pharyngeal diameter necessary to fit the pressure-flow data is quite small (0.11-0.87 cm, depending on the assumptions in the model). The flow-related increase in orifice area can be attributed, in part, to the activation of the genioglossus muscle. However, other flow-related factors may also contribute to pharyngeal dilation as airflow increases. Different airway shapes (circular and elliptical) and orientations (major axis anteroposterior and lateral) were incorporated into the model calculations; these factors modify considerably the apparent efficiency of genioglossal electromyographic activity. Genioglossal muscle shortening increases pharyngeal area and reduces pharyngeal resistance more effectively when the pharynx is elliptical, with the long axis of the ellipse oriented laterally. Hence the genioglossus may operate at a significant mechanical disadvantage in those patients with obstructive sleep apnea with a small sagittally oriented pharyngeal lumen.     

Segmental barrier properties of the pulmonary microvascular bed.

We determined liquid flux across single pulmonary microvessels of dog, ferret, and rat by our split-drop technique (J. Appl. Physiol. 64: 2562-2567, 1988). Data are reported from 58 lungs excised under halothane or pentobarbital sodium anesthesia and then blood perfused. We stopped blood flow at known vascular pressures and then micropunctured microvessels to inject oil, which we split with albumin solution. From measurements of vessel diameter and split oil drop length, we calculated Jv, the liquid transport rate per unit surface area [x 10(-6) ml/(cm2.s)]. At constant vascular pressure, Jv was not significantly different after different periods of oil-endothelium contact and at different sites within a single vessel. From measurements of Jv at different vascular pressures, we determined Lp, the hydraulic conductivity [x 10(-7) ml/(cm2.s.cmH2O)], and Pzf, the zero filtration pressure. From determinations of Pzf at different albumin concentrations, we quantified sigma alb, the albumin reflection coefficient. Lp and Pzf did not differ among venules of the same lung. However, in venules, Lp was 40% higher and sigma alb 25% lower than in arterioles (P less than 0.01). We conclude that 1) micropuncture procedures incidental to our split-drop technique do not progressively deteriorate the experimental microvessel and 2) in lung, permeability is higher in venules than in arterioles.     

Effects of adenosine on pressure-flow relationships in an in vitro model of compartment syndrome

Shrier, Ian, Ari Baratz, and Sheldon Magder. Effects ofadenosine on pressure-flow relationships in an in vitro model ofcompartment syndrome. J. Appl.Physiol. 82(3): 755-759, 1997.Blood flow throughskeletal muscle is best modeled with a vascular waterfall at thearteriolar level. Under these conditions, flow is determined by thedifference between perfusion pressure (Pper) and the waterfall pressure(Pcrit), divided by the arterial resistance (Ra). By pump perfusing anisolated canine gastrocnemius muscle(n = 6) after it was placed within anairtight box, with and without adenosine infusion, we observed aninteraction between the pressure surrounding a muscle (as occurs incompartment syndrome) and baseline vascular tone. Wetitrated adenosine concentration to double baseline flow. We measuredPcrit and Ra at box pressures (Pbox), which resulted in 100 (Pbox = 0),90, 75, and 50% flow without adenosine; and 200, 180, 150, 100, and50% flow with adenosine. Without adenosine, each 10% decline in flowwas associated with a 5.7 mmHg increase in Pcrit(P < 0.01). With adenosine, the samedecrease in flow was associated with a 2.6-mmHg increase in Pcrit(P < 0.01). Values of Pcrit at 50%of flow were almost identical. Each 10% decrease in flow was alsoassociated with 2.2% increase in Ra with or without adenosine(P < 0.001). Ra decreased withadenosine infusion (P < 0.05), andthere was no interaction between adenosine and flow (P > 0.9). We conclude thatincreases in pressure surrounding a muscle limit flow primarily throughchanges in Pcrit with and without adenosine-induced vasodilation. Theinteraction between Pbox and adenosine with respect to Pcrit but not Rasuggests that Pbox affects the tone of the vessels responsible forPcrit but not Ra.

     

Ultrastructural appearances of pulmonary capillaries at high transmural pressures.

Electronmicroscopic appearances of pulmonary capillaries were studied in rabbit lungs perfused in situ when the capillary transmural pressure (Ptm) was systematically raised from 12.5 to 72.5 +/- 2.5 cmH2O. The animals were anesthetized and exsanguinated, and after the chest was opened, the pulmonary artery and left atrium were cannulated and attached to reservoirs. The lungs were perfused with autologous blood for 1 min, and this was followed by saline-dextran and then buffered glutaraldehyde to fix the lungs for electron microscopy. Normal appearances were seen at 12.5 cmH2O Ptm. At 52.5 and 72.5 cmH2O Ptm, striking discontinuities of the capillary endothelium and alveolar epithelium were seen. A few disruptions were seen at 32.5 cmH2O Ptm (mostly in one animal), but the number of breaks per millimeter cell lining increased markedly up to 72.5 cmH20 Ptm, where the mean frequency was 27.8 +/- 8.6 and 13.6 +/- 1.4 (SE) breaks/mm for endothelium and epithelium, respectively. In some instances, all layers of the blood-gas barrier were disrupted and erythrocytes could be seen moving into the alveolar spaces. In about half the endothelial and epithelial breaks, the basement membranes remained intact. The average break lengths for both endothelium and epithelium did not change significantly with pressure. The width of the blood-gas barrier increased at 52.5 and 72.5 cmH2O Ptm as a result of widening of the interstitium caused by edema. The cause of the disruptions is believed to be stress failure of the capillary wall. The results show that high capillary hydrostatic pressures cause major changes in the ultrastructure of the walls of the capillaries, leading to a high-permeability form of edema.     

Flow-induced vasodilation in the ferret lung

Chammas, Joseph H., David. A. Rickaby, Margarita Guarin,John H. Linehan, Christopher C. Hanger, and Christopher A. Dawson. Flow-induced vasodilation in the ferret lung. J. Appl. Physiol. 83(2): 495-502, 1997.To examinethe possibility that shear stress may be a pulmonary vasodilatorstimulus, we studied the effect of changing blood flow on the diametersof small pulmonary arteries in isolated perfused ferret lung lobes. Thearteries studied were in the ~0.3- to 1.3-mm-diameter range, and thediameters were measured by using microfocal X-ray imaging. Thediameters were measured at two flow rates, 10 and 40 ml/min, with theintravascular pressure in the measured vessels the same at the two flowrates as the result of venous pressure adjustment. The response to a change in flow was studied under both normoxic and hypoxic conditions. Hypoxia was used to elevate pulmonary arterial tone to increase thelikelihood of detecting a vasodilator response. Under normoxic conditions, changing flow had little effect on the arterial diameters, but under hypoxic conditions the arteries were consistently larger atthe higher flow than at the lower flow, even though the distending pressure was the same at the two flow rates. The results are consistent with the hypothesis that shear stress is a pulmonary vasodilator stimulus.

     

Compared responses of rat lungs to step volume changes and to sinusoidal forcing.

Lung pressure-volume hysteresis of cat lungs has been found by Hildebrandt (J. Appl. Physiol. 28, 365-372, 1970) to be 20-50% larger than predicted from stress adaptation data on the basis of a viscoelastic model. We have reinvestigated this phenomenon in isolated rat lungs with a different approach, in which the approximation inherent to using a model is avoided : Lung transfer function was derived from the digitally-computed Laplace transform of the pressure decay following a step volume change and used to predict lung pressure-flow relationship in the frequency domain. The latter was expressed in terms of lung effective resistance (Rlc) and effective elastance (Elc), and compared to the observed values (Rl and El) in the frequency range 0.01-0.5 Hz. The measurements were made in 5 lungs at a transpulmonary pressure (Pl) of 0.5 kPa and in 5 others at a Pl of 0.8 kPa. Rl was found to be 23-41% larger than Rlc at Pl = 0.5 and 29-51% larger at Pl = 0.8. El did not differ significantly from Elc at Pl = 0.5 but was 14-28% larger at Pl = 0.8. These results are in good agreement with previous findings. The differences between Rl and Rlc are proportional to the reciprocal of frequency and, thus, correspond to a rate-independent dissipation. They are consistent with a yield stress of 3-6 Pa.