Filtration profile in isolated zone 1 and zone 3 dog lungs at constant high alveolar pressure

We measured the rate of liquid filtration in isolated dog lung lobes inflated to a constant alveolar pressure of 25 cmH2O and with all open vessels filled with plasma. We measured lung weight gain at vascular pressures ranging from 5 to 40 cmH2O relative to pleural pressure. We confirmed that under zone 1 conditions the "arterial" and "venous" extra-alveolar segments have essentially the same filtration characteristics. Using the combined extra-alveolar vascular system, we determined when recruitment of filtration surface area occurred as we increased vascular pressure from 0 to 40 cmH2O. Based on an abrupt increase in filtration rate as vascular pressure approached the zone 1/3 boundary, we infer that a sudden recruitment of exchange surface area occurred at that point. Based on the slopes of the zone 1 and zone 3 filtration profiles, we conclude that extra-alveolar vascular segments contribute approximately 25% of total to filtration in the lung under zone 3 conditions, although the exact vessels filtering under zone 1 conditions have yet to be determined. Our analysis of the data supports the concept that there is a difference in the perimicrovascular pressure around alveolar and extra-alveolar vessels, which in part may account for the apparent high filtration fraction apportioned to extra-alveolar vessels.     

Extra-alveolar vessel fluid filtration coefficients in excised and in situ canine lobes

We continuously weighed fully distended excised or in situ canine lobes to estimate the fluid filtration coefficient (Kf) of the arterial and venous extra-alveolar vessels compared with that of the entire pulmonary circulation. Alveolar pressure was held constant at 25 cmH2O after full inflation. In the in situ lobes, the bronchial circulation was interrupted by embolization. Kf was estimated by two methods (Drake and Goldberg). Extra-alveolar vessels were isolated from alveolar vessels by embolizing enough 37- to 74-micron polystyrene beads into the lobar artery or vein to completely stop flow. In excised lobes, Kf's of the entire pulmonary circulation by the Drake and Goldberg methods were 0.122 +/- 0.041 (mean +/- SD) and 0.210 +/- 0.080 ml X min-1 X mmHg-1 X 100 g lung-1, respectively. Embolization was not found to increase the Kf's. The mean Kf's of the arterial extra-alveolar vessels were 0.068 +/- 0.014 (Drake) and 0.069 +/- 0.014 (Goldberg) (24 and 33% of the Kf's for the total pulmonary circulation). The mean Kf's of the venous extra-alveolar vessels were similar [0.046 +/- 0.020 (Drake) and 0.065 +/- 0.036 (Goldberg) or 33 and 35% of the Kf's for the total circulation]. No significant difference was found between the extra-alveolar vessel Kf's of in situ vs. excised lobes. These results suggest that when alveolar pressure, lung volume, and pulmonary vascular pressures are high, approximately one-third of the total fluid filtration comes from each of the three compartments.     

Growth rate of perivascular cuffs in liquid-inflated dog lung lobes

In the early stages of pulmonary edema, excess liquid leaving the pulmonary exchange vessels accumulates in the peribronchovascular interstitium where it forms large peribronchovascular cuffs. The peribronchovascular interstitium therefore acts as a reservoir to protect the air spaces from alveolar flooding. The rate of liquid accumulation and the liquid storage capacity of the cuffs determine how quickly alveolar flooding is likely to follow once edema formation has begun. To measure the rate and capacity of interstitial filling we inflated 11 isolated degassed dog lung lobes with liquid to an inflation pressure of 14 cmH2O (total lung capacity) for 1-300 min, then froze the lobes in liquid N2. We made photographs of 20 randomly selected 12 X 8-mm cross sections from each lobe and measured cuff volume from the photographs by point-counting. We found that cuff volume increased from 2.2% of air-space volume after 1 min of inflation to 9.3% after 300 min. To measure the driving pressure responsible for cuff formation we used micropipettes to measure subpleural interstitial liquid pressure at the hilum of three additional lobes. With liquid inflation pressure set to 14 cmH2O interstitial pressure rose exponentially to 11.5 cmH2O. Interstitial compliance calculated from our volume and pressure measurements equaled 0.09 ml X cmH2O-1 X g wet wt-1, a value similar to that measured in air-inflated lungs. Goldberg [Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H189-H198, 1980] has likened interstitial filling to the charging of a capacitor, a process that follows a monoexponential time course.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of dehydration on interstitial pressures in the isolated dog lung

We have determined the effect of dehydration on regional lung interstitial pressures. We stopped blood flow in the isolated blood-perfused lobe of dog lung at vascular pressure of approximately 4 cmH2O. Then we recorded interstitial pressures by micropuncture at alveolar junctions (Pjct), in perimicrovascular adventitia (Padv), and at the hilum (Phil). After base-line measurements, we ventilated the lobes with dry gas to decrease extravascular lung water content by 14 +/- 5%. In one group (n = 10), at constant inflation pressure of 7 cmH2O, Pjct was 0.2 +/- 0.8 and Padv was -1.5 +/- 0.6 cmH2O. After dehydration the pressures fell to -5.0 +/- 1.0 and -5.3 +/- 1.3 cmH2O, respectively (P less than 0.01), and the junction-to-advential gradient (Pjct-Padv) was abolished. In a second group (n = 6) a combination of dehydration and lung expansion with inflation pressure of 15 cmH2O further decreased Pjct and Padv to -7.3 +/- 0.7 and -7.1 +/- 0.7 cmH2O, respectively. Phil followed changes in Padv. Interstitial compliance was 0.6 at the junctions, 0.8 in adventitia, and 0.9 ml.cmH2O-1.100 g-1 wet lung at the hilum. We conclude, that perialveolar interstitial pressures may provide an important mechanism for prevention of lung dehydration.     

Effects of inspiratory resistance loading on lung fluid balance in awake sheep

Because pulmonary edema has been associated clinically with airway obstruction, we sought to determine whether decreased intrathoracic pressure, created by selective inspiratory obstruction, would affect lung fluid balance. We reasoned that if decreased intrathoracic pressure caused an increase in the transvascular hydrostatic pressure gradient, then lung lymph flow would increase and the lymph-to-plasma protein concentration ratio (L/P) would decrease. We performed experiments in six awake sheep with chronic lung lymph cannulas. After a base-line period, we added an inspiratory load (20 cmH2O) and allowed normal expiration at atmospheric pressure. Inspiratory loading was associated with a 12-cmH2O decrease in mean central airway pressure. Mean left atrial pressure fell 11 cmH2O, and mean pulmonary arterial pressure was unchanged; calculated microvascular pressure decreased 8 cmH2O. The changes that occurred in lung lymph were characteristic of those seen after other causes of increased transvascular hydrostatic gradient, such as increased intravascular pressure. Lung lymph flow increased twice base line, and L/P decreased. We conclude that inspiratory loading is associated with an increase in the pulmonary transvascular hydrostatic gradient, possibly by causing a greater fall in interstitial perimicrovascular pressure than in microvascular pressure.     

Continuity of arterial and venous extra-alveolar interstitium in excised rabbit lungs

We studied the interdependence of arterial and venous extra-alveolar vessel (EAV) leakage on the rate of pulmonary vascular fluid filtration (measured as the change in lung weight over time). Edema was produced in continually weighed, excised rabbit lungs kept in zone 1 (alveolar pressure = 25 cmH2O) by increasing pulmonary arterial (Ppa) and/or venous (Ppv) pressure from 5 to 20 cmH2O (relative to the lung base) and continuing this hydrostatic stress for 3-5 h. Raising Ppa and Ppv simultaneously produced a lower filtration rate than the sum of the filtration rates obtained when Ppa and Ppv were raised separately, while the lung gained from 20 to 95% of its initial weight. When vascular pressure was elevated in either EAV segment, fluid filtration always decreased rapidly as the lung gained up to 30-45% of its initial weight. Filtration then decreased more slowly. The lungs became isogravimetric at 60 and 85% weight gain when the Ppa or Ppv was elevated, respectively; when Ppa and Ppv were raised simultaneously substantial fluid filtration continued even after 140% weight gain. We conclude that the arterial and venous EAV's share a common interstitium in the zone 1 condition, this interstitium cannot be represented as a single compartment with a fixed resistance and compliance, and arterial and venous EAV leakage influences leakage from the other segment.     

Extra-alveolar veins are contiguous with, and leak fluid into, periarterial cuffs in rabbit lungs.

We previously observed physiological evidence that arterial and venous extra-alveolar vessels shared a common interstitial space. The purpose of the present investigation was to determine the site of this continuity to improve our understanding of interstitial fluid movement in the lung. Orange G and Evans blue dyes were added to the arterial and venous reservoirs, respectively, of excised rabbit lungs as they were placed 20 cmH2O into zone 1 (pulmonary arterial and venous pressures = 5 cmH2O, alveolar pressure = 25 cmH2O). After 10 s or 4 h the lungs were fixed by immersion in liquid N2, freeze-dried, cut into 5-mm serial slices, and examined by light macroscopy. Serial sections of 0.25-0.5 mm were subsequently examined by scanning electron microscopy. In the animals subjected to the zone 1 stress for 4 h, arterial and venous extra-alveolar vessels were surrounded by cuffs of edema. The edema ratio (cuff area divided by vessel lumen area) was greater around arteries than veins and decreased with increasing vessel size. Periarterial cuffs usually contained orange dye and frequently contained both orange and blue dye. Lymphatics containing orange or blue dye were frequently seen in periarterial cuffs. Scanning electron microscopy demonstrated that extra-alveolar veins of approximately 100 microns diameter were anatomically contiguous with arterial extra-alveolar vessel cuffs. In rabbit lungs, both arterial and venous extra-alveolar vessels (and/or alveolar corner vessels) leak fluid into perivascular cuffs surrounding arterial extra-alveolar vessels, and lymphatics located in the periarterial cuff contain fluid that originates from both the arterial and venous extra-alveolar vessels.     

Lung edema increases transvascular filtration rate but not filtration coefficient

To determine whether the accelerated rate of lobe weight gain during severe pulmonary edema is attributed to increased permeability of the microvascular barrier or a loss of tissue forces opposing filtration, the effect of edema on capillary filtration coefficient (Kf,C), interstitial compliance (Ci), and the volume of fluid filtered after a step increase in microvascular pressure (delta Vi) were determined in eight isolated left lower lobes of dog lungs perfused at 37 degrees C with autologous blood. After attaining a base-line isogravimetric state, the capillary pressure (Pc) was increased in successive steps of 2, 5, and 10 cmH2O. This sequence of vascular pressure increases was repeated three times. Edema accumulation was expressed as weight gained as a percent of initial lobe weight (% delta Wt), and Kf,C was measured by time 0 extrapolation of the weight gain curve. An exponential rate constant for the decrease in the rate of weight gain with time (K) was calculated for each curve. Ci was then calculated by assuming that the capillary wall and interstitium constitute a resistance-capacitance network. Kf,C was not increased by edema formation in any group. Between mild (% delta Wt less than 30%) and severe edema states (% delta Wt greater than 50%) respective mean Ci increased significantly from 3.54 to 9.12 ml.cmH2O-1.100 g-1, K decreased from 0.089 to 0.036 min-1, and delta Vi increased from 1.28 to 2.4 ml.cmH2O-1.100 g-1. The delta Vi during each Pc increase was highly correlated with Kf,C and Ci when used together as independent variables (r = 0.99) but less well correlated when used separately.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interstitial fluid pressure gradient measured by micropuncture in excised dog lung

We have directly measured lung interstitial fluid pressure at sites of fluid filtration by micropuncturing excised left lower lobes of dog lung. We blood-perfused each lobe after cannulating its artery, vein, and bronchus to produce a desired amount of edema. Then, to stop further edema, we air-embolized the lobe. Holding the lobe at a constant airway pressure of 5 cmH2O, we measured interstitial fluid pressure using beveled glass micropipettes and the servo-null method. In 31 lobes, divided into 6 groups according to severity of edema, we micropunctured the subpleural interstitium in alveolar wall junctions, in adventitia around 50-micron venules, and in the hilum. In all groups an interstitial fluid pressure gradient existed from the junctions to the hilum. Junctional, adventitial, and hilar pressures, which were (relative to pleural pressure) 1.3 +/- 0.2, 0.3 +/- 0.5, and -1.8 +/- 0.2 cmH2O, respectively, in nonedematous lobes, rose with edema to plateau at 4.1 +/- 0.4, 2.0 +/- 0.2, and 0.4 +/- 0.3 cmH2O, respectively. We also measured junctional and adventitial pressures near the base and apex in each of 10 lobes. The pressures were identical, indicating no vertical interstitial fluid pressure gradient in uniformly expanded nonedematous lobes which lack a vertical pleural pressure gradient. In edematous lobes basal pressure exceeded apical but the pressure difference was entirely attributable to greater basal edema. We conclude that the presence of an alveolohilar gradient of lung interstitial fluid pressure, without a base-apex gradient, represents the mechanism for driving fluid flow from alveoli toward the hilum.     

Interaction of chemical and high vascular pressure injury in isolated canine lung

Because both chemical and mechanical insults to the lung may occur concomitantly with trauma, we hypothesized that the pressure threshold for vascular pressure-induced (mechanical) injury would be decreased after a chemical insult to the lung. Normal isolated canine lung lobes (N, n = 14) and those injured with either airway acid instillation (AAI, n = 18) or intravascular oleic acid (OA, n = 25) were exposed to short (5-min) periods of elevated venous pressure (HiPv) ranging from 19 to 130 cmH2O. Before the HiPv stress, the capillary filtration coefficient (Kf,c) was 0.12 +/- 0.01, 0.27 +/- 0.03, and 0.31 +/- 0.02 ml.min-1.cmH2O-1 x 100 g-1 and the isogravimetric capillary pressure (Pc,i) was 9.2 +/- 0.3, 6.8 +/- 0.5, and 6.5 +/- 0.3 cmH2O in N, AAI, and OA lungs, respectively. However, the pattern of response to HiPv was similar in all groups: Kf,c was no different from the pre-HiPv value when the peak venous pressure (Pv) remained less than 55 cmH2O, but it increased reversibly when peak Pv exceeded 55 cmH2O (P less than 0.05). The reflection coefficient (sigma) for total proteins measured after pressure exposure averaged 0.60 +/- 0.03, 0.32 +/- 0.04, and 0.37 +/- 0.09 for N, AAI, and OA lobes respectively. However, in contrast to the result expected if pore stretching had occurred at high pressure, in all groups the sigma measured during the HiPv stress when Pv exceeded 55 cmH2O was significantly larger than that measured during the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lung expansion and the perialveolar interstitial pressure gradient

We have determined the combined effects of lung expansion and increased extravascular lung water (EVLW) on the perialveolar interstitial pressure gradient. In the isolated perfused lobe of dog lung, we measured interstitial pressures by micropuncture at alveolar junctions (Pjct) and in adventitia of 30- to 50-microns microvessels (Padv) with stopped blood flow at vascular pressure of 3-5 cmH2O. We induced edema by raising vascular pressures. In nonedematous lobes (n = 6, EVLW = 3.1 +/- 0.3 g/g dry wt) at alveolar pressure of 7 cmH2O, Pjct averaged 0.5 +/- 0.8 (SD) cmH2O and the Pjct-Padv gradient averaged 0.9 +/- 0.5 cmH2O. After increase of alveolar pressure to 23 cmH2O the gradient was abolished in nonedematous lobes, did not change in moderately edematous lobes (n = 9, EVLW = 4.9 +/- 0.6 g/g dry wt), and increased in severely edematous lobes (n = 6, EVLW = 7.6 +/- 1.4 g/g dry wt). Perialveolar interstitial compliance decreased with increase of alveolar pressure. We conclude that increase of lung volume may reduce perialveolar interstitial liquid clearance by abolishing the Pjct-Padv gradient in nonedematous lungs and by compressing interstitial liquid channels in edematous lungs.     

Micropuncture measurement of alveolar liquid pressure in excised dog lung lobes

We have investigated the mechanism of alveolar liquid filling in pulmonary edema. We excised, degassed, and intrabronchially filled 14 dog lung lobes from nine dogs with 75, 150, 225, or 350 ml of 5% albumin solution, and then air inflated the lobes to a constant airway pressure of 25 cmH2O. By use of micropipettes, we punctured subpleural alveoli to measure alveolar liquid pressure by the servo-null technique. Alveolar liquid pressure was constant in all lobes despite differences in lobe liquid volume and averaged 10.6 +/- 1.3 cmH2O. Thus, in all lobes a constant pressure drop of 14.4 cmH2O existed from airway to alveolar liquid across the air-liquid interface. We attribute this finding, on the basis of the Laplace equation, to an air-liquid interface of constant radius in all the lobes. In fact, we calculated from the Laplace equation an air-liquid interface radius which equalled morphological estimates of alveolar radius. We conclude that in the steady state, alveoli that contained liquid have a constant radius of curvature of the air-liquid interface possibly because they are always completely liquid filled.     

Promethazine or DPPD pretreatment attenuates oleic acid-induced injury in isolated canine lungs

Oleic acid causes pulmonary edema by increasing capillary endothelial permeability, although the mechanism of this action is uncertain. We tested the hypothesis that the damage is an oxidant injury initiated by oleic acid, using isolated blood-perfused canine lung lobes. The lobes were dilated with papaverine and perfused in zone III with a constant airway pressure of 3 cmH2O. Changes in isogravimetric capillary pressure (Pc,i) and capillary filtration coefficient (Kf,C) were used as indices of alterations in microvascular permeability in lungs treated with silicone fluid (n = 3), oleic acid (n = 11), oleic acid after pretreatment with the antioxidants promethazine HCl (n = 11) or N,N'-diphenyl-p-phenylenediamine (DPPD; n = 4), or oleic acid following pretreatment with methylprednisolone (n = 4). Kf,C averaged 0.21 +/- 0.02 ml X min-1 X cmH2O-1 X 100 g-1 in control and increased to 0.55 +/- 0.05 and 0.47 +/- 0.05 when measured 20 and 180 min after the administration of oleic acid. When oleic acid was infused into lungs pretreated with promethazine, Kf,C increased to only 0.38 +/- 0.05 ml X min-1 X cmH2O-1 X 100 g-1 after 20 min and had returned to control levels by 180 min. Pretreatment with DPPD, but not methylprednisolone, similarly attenuated the increase in Kf,C following oleic acid. Silicone fluid had no effect on Kf,C. That oleic acid increases vascular permeability was also evidenced by a fall (P less than 0.05) in Pc,i from control when measured at 180 min in every group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Venous occlusion pressure and vascular permeability in the dog lung after air embolization

Pulmonary edema has frequently been associated with air embolization of the lung. In the present study the hemodynamic effects of air emboli (AE) were studied in the isolated mechanically ventilated canine right lower lung lobe (RLL), pump perfused at a constant blood flow. Air was infused via the pulmonary artery (n = 7) at 0.6 ml/min until pulmonary arterial pressure (Pa) rose 250%. While Pa rose from 12.4 +/- 0.6 to 44.6 +/- 2.0 (SE) cmH2O (P less than 0.05), venous occlusion pressure remained constant (7.0 +/- 0.5 to 6.8 +/- 0.6 cmH2O; P greater than 0.05). Lobar vascular resistance (RT) increased from 2.8 +/- 0.3 to 12.1 +/- 0.2 Torr.ml-1.min.10(-2) (P less than 0.05), whereas the venous occlusion technique used to determine the segmental distribution of vascular resistance indicated the increase in RT was confined to vessels upstream to the veins. Control lobes (n = 7) administered saline at a similar rate showed no significant hemodynamic changes. As an index of microvascular injury the pulmonary filtration coefficient (Kf) was obtained by sequential elevations of lobar vascular pressures. The Kf was 0.11 +/- 0.01 and 0.07 +/- 0.01 ml.min-1.Torr-1.100 g RLL-1 in AE and control lobes, respectively (P less than 0.05). Despite a higher Kf in AE lobes, total lobe weight gains did not differ and airway fluid was not seen in the AE group. Although air embolization caused an increase in upstream resistance and vascular permeability, venous occlusion pressure did not increase, and marked edema did not occur.     

Filtration coefficient obtained by stepwise pressure elevation in isolated dog lung

The base-line capillary filtration coefficient (Kf) obtained from rates of lobe weight gain during stepwise vascular pressure elevation is reported to be threefold greater in isolated than in intact dog lung. To further evaluate the stepwise pressure elevation technique, we obtained Kf in control and oleic acid-injured isolated lung. The left lower lung lobe was removed, placed on a balance, ventilated, and pump perfused with autogenous blood. Saline (n = 6) or oleic acid (n = 6) was infused, and rate of lobe weight gain was obtained during stepwise pressure elevation. Kf averaged 0.071 +/- 0.012 and 0.243 +/- 0.027 ml X min-1 X Torr-1 X 100 g-1 in the control and injured lobes, respectively. Stepwise pressure elevation can yield a base-line Kf in isolated lung similar to Kf's obtained from this and other gravimetric methods in intact and isolated lung. Furthermore, Kf increased severalfold following lung injury with oleic acid. The stepwise pressure elevation technique for Kf determination in isolated lung can be a useful tool for quantitating changes in vascular permeability.     

Pulmonary hemodynamics and gas exchange properties during progressive edema

In this investigation we have studied the effect of increments of pulmonary edema on pulmonary hemodynamics, and physiological and hemodynamic shunt in an isolated lung preparation. Hemodynamic shunt was defined by the slope of the relationship between pulmonary arterial and airway pressures; when the slope decreases, there is a greater degree of shunt. Cardiovascular changes were analyzed using a Starling resistor model of the pulmonary circulation where the effective downstream pressure to flow as seen from the pulmonary artery exceeds the pulmonary venous outflow pressure. This effective downstream pressure is referred to as the critical pressure (Pc), and at low lung inflation the locus of this critical pressure is in extra-alveolar vessels. With 3-4 h of progressive edema to an average of 185% initial lobe weight we found a progressive rise in pulmonary arterial pressure (Ppa) from 12.1 to 21.5 cmH2O. About one-third of this increase in Ppa resulted from an increased Pc and the remainder resulted from an increased resistance upstream from the locus of Pc. These results are consistent with the hypothesis that the interstitial accumulation of fluid creates enough of an increase in interstitial pressure to compress extra-alveolar vessels. There was no significant correlation between the amount of edema and the measured physiologic shunt, but the hemodynamic shunt showed a highly significant correlation. The hemodynamic shunt theoretically measures the extent of obstructed airways and may be a useful index of the degree of pulmonary edema.     

Parenchymal interdependence and airway response to methacholine in excised dog lobes

The objective of this investigation was to determine the minimum transpulmonary pressure (PL) at which the forces of interdependence between the airways and the lung parenchyma can prevent airway closure in response to maximal stimulation of the airways in excised canine lobes. We first present an analysis of the relationship between PL and the transmural pressure (Ptm) that airway smooth muscle must generate to close the airways. This analysis predicts that airway closure can occur at PL less than or equal to 10 cmH2O with maximal airway stimulation. We tested this prediction in eight excised canine lobes by nebulizing 50% methacholine into the airways while the lobe was held at constant PL values ranging from 25 to 5 cmH2O. Airway closure was assessed by comparing changes in alveolar pressure (measured by an alveolar capsule technique) and pressure at the airway opening during low-amplitude oscillations in lobar volume. Airway closure occurred in two of the eight lobes at PL = 10 cmH2O; in an additional five it occurred at PL = 7.5 cmH2O. We conclude that the forces of parenchymal interdependence per se are not sufficient to prevent airway closure at PL less than or equal to 7.5 cmH2O in excised canine lobes.     

Osmotic reflection coefficient for total plasma protein in lung microvessels

The osmotic reflection coefficient (sigma) for total plasma proteins was estimated in 11 isolated blood-perfused canine lungs. Sigma's were determined by first measuring the capillary filtration coefficient (Kf,C in ml X min-1 X 100g-1 X cmH2O-1) using increased hydrostatic pressures and time 0 extrapolation of the slope of the weight gain curve. Kf,C averaged 0.19 +/- 0.05 (mean +/- SD) for 14 separate determinations in the 11 lungs. Following a Kf,C determination, the isogravimetric capillary pressure (Pc,i) was determined and averaged 9.9 +/- 0.5 cmH2O for all controls reported in this study. Then the blood colloids in the perfusate were either diluted or concentrated. The lung either gained or lost weight, respectively, and an initial slope of the weight gain curve (delta W/delta t)0 was estimated. The change in plasma protein colloid osmotic pressure (delta IIP) was measured using a membrane osmometer. The measured delta IIP was related to the effective colloid osmotic pressure (delta IIM) by delta IIM = (delta W/delta t)0/Kf,C = sigma delta IIP. Using this relationship, sigma averaged 0.65 +/- 0.06, and the least-squares linear regression equation relating Pc,i and the measured IIP was Pc,i = -3.1 + 0.67 IIP. The mean estimate of sigma (0.65) for total plasma proteins is similar to that reported for dog lung using lymphatic protein flux analyses, although lower than estimates made in skeletal muscle using the present methods (approximately 0.95).     

Segmental vascular resistances and compliances in dog lung

The segmental distribution of vascular resistances and compliances were evaluated in isolated blood perfused lung lobes using arterial, venous, and double-occlusion pressures and were compared with filtration midpoint capillary pressures (Pc,f). We separated total vascular resistance (RT) and compliance (CT) into large artery (Ra, Ca), large vein (Rv, Cv), and microvascular compartments (Rmc, Cmc) at base-line and increased vascular pressures and during infusions of histamine, serotonin, and norepinephrine. In control lobes, double-occlusion pressure (Pdo) closely approximated Pc,f at all vascular pressures. Pre- and postcapillary resistance were approximately equal when referenced to either Pc,f or Pdo. Although Rmc comprised 42% of RT and Cmc constituted 76% of CT, a twofold increase in base-line Pc,f caused RT to decrease to 67% and Rmc/RT to 29% of control values, whereas CT decreased to 87% and Cmc/CT decreased to 88% of control values over the same Pc,f range. Mean static CT was 2.25 +/- 0.09 ml X cmH2O-1. 100 g-1, whereas dynamic CT was 1.54 +/- 0.08 ml X cmH2O-1. 100 g-1, or only 68% of static vascular compliance. Drug infusions increased mean RT from 4.2- to 5.3-fold and significantly decreased both static and dynamic CT. Although all vascular segments were constricted, histamine affected primarily large veins, serotonin increased Ra greater than Rv, and norepinephrine constricted upstream and downstream vessels about equally. Increased Pc,f in the presence of these drugs decreased RT significantly in every case primarily through attenuation of the drug vasoconstrictor effect on Rmc and decreased CT primarily due to a decrease in Cmc, but increased Cmc/(Ca + Cv). Thus the microvascular compartment appears to be the major site of both fluid filtration and vascular compliance and contributes significantly to total vascular resistance. Drug infusions constricted large and small vessel compartments as defined here, but increased Pc,f attenuated microvascular vasoconstriction and to a lesser extent large vessel vasoconstriction resulting in a reduced microvascular resistance in both drug-treated and control lobes. This effect can be attributed to recruitment and/or distension of microvessels and distension of larger vessels.     

Fast-phase transvascular fluid flux and the Fahraeus effect

Transvascular fluid flux was induced in six isolated blood-perfused canine lobes by increasing and decreasing hydrostatic inflow pressure (Pi). Fluid flux was followed against the change in concentration of an impermeable tracer (Blue Dextran) measured directly with a colorimetric device. The time course of fluid flux was biphasic with an initial fast transient followed by a slow phase. Hematocrit changes unrelated to fluid flux occurred due to the Fahraeus effect, and their contribution to the total color signal was subtracted to determine the rate of fast fluid flux (Qf). Qf was related to Pi to derive fast-phase conductance (Kf). Slow-phase Kf was calculated from the constant rate of change of lobe weight. For a mean change in Pi of 7 cmH2O, 40% of the color signal was due to fluid flux. Fast- and slow-phase Kf's were 0.86 +/- 0.15 and 0.27 +/- 0.05 ml X min-1. cmH2O-1 X 100 g dry wt-1. The fast-phase Kf is smaller than that reported for plasma-perfused lobes. Possible explanations discussed are the nature of the perfusate, the mechanical properties of the interstitium, and the slow rate of rise of the driving pressure at the filtration site on the basis of a distributed model of pulmonary vascular compliance.