Effect of airway and left atrial pressures on microcirculation of newborn lungs

To determine the effect of lung inflation and left atrial pressure on the hydrostatic pressure gradient for fluid flux across 20- to 60-microns-diam venules, we isolated and perfused the lungs from newborn rabbits, 7-14 days old. We used the micropuncture technique to measure venular pressures in some lungs and perivenular interstitial pressures in other lungs. For all lungs, we first measured venular or interstitial pressures at a constant airway pressure of 5 or 15 cmH2O with left atrial pressure greater than airway pressure (zone 3). For most lungs, we continued to measure venular or interstitial pressures as we lowered left atrial pressure below airway pressure (zone 2). Next, we inflated some lungs to whichever airway pressure had not been previously used, either 5 or 15 cmH2O, and repeated venular or interstitial pressures under one or both zonal conditions. We found that at constant blood flow a reduction of left atrial pressure below airway pressure always resulted in a reduction in venular pressure at both 5 and 15 cmH2O airway pressures. This suggests that the site of flow limitation in zone 2 was located upstream of venules. When left atrial pressure was constant relative to airway pressure, the transvascular gradient (venular-interstitial pressures) was greater at 15 cmH2O airway pressure than at 5 cmH2O airway pressure. These findings suggest that in newborn lungs edema formation would increase at high airway pressures only if left atrial pressure is elevated above airway pressure to maintain zone 3 conditions.     

Alveolar liquid pressure in excised edematous dog lung with increased static recoil

Alveolar liquid pressure (Pliq) was measured by micropipettes in conjunction with a servo-nulling pressure measuring system in isolated air-inflated edematous dog lungs. Pliq was measured in lungs either washed with a detergent (0.01% Triton X-100) or subjected to refrigeration for 2-3 days followed by ventilation for 3 h. At 55% of total lung capacity (TLC, the volume at a transpulmonary pressure (Ptp) of 25 cmH2O before treatment), in both the Triton-washed and the ventilated lung, Ptp increased from 5 to 11 cmH2O, whereas Pliq, decreased from -3 to -11 cmH2O relative to alveolar air pressure. Similar increases in Ptp and decreases in Pliq were obtained at higher lung volumes. Alveolar surface tension (T) was estimated from the Laplace equation for a spherical air-liquid interface, assuming that the radius of curvature varies as (volume)n, for -1/3 less than n less than 1/3. For uniform expansion of alveoli (n = 1/3), estimated T was 6 and 18 dyn/cm at 55 and 85% TLC, respectively, before treatment and increased to 23 and 40 dyn/cm following either Triton washing or ventilation. If pericapillary interstitial fluid pressure (Pi) equaled Pliq in edematous lungs, increases in T might reduce Pi and increase extravascular fluid accumulation in lungs made stiff by either Triton washing or cooling and ventilation using large tidal volumes.     

Sites of leakage in three models of acute lung injury

Fluid leaking from arterial and venous extra-alveolar vessels (EAV's) may account for up to 60% of the total transvascular fluid flux when edema occurs in the setting of normal vascular permeability. We determined if the permeability and relative contribution of EAV's was altered after inducing acute lung injury in rabbits by administering oleic acid (0.1 ml/kg) into the pulmonary artery, HCl (5 ml/kg of 0.1 N) into the trachea, or air emboli (0.03 ml.kg-1.min-1) into the right atrium for 90 min. Subsequently, the lungs were excised and continuously weighed while they were maintained in a warmed, humidified chamber with alveolar and pulmonary vascular pressures controlled and the lungs either ventilated or distended with 5% CO2 in air. The vascular system was filled with autologous blood and saline (1:1) to which papaverine (0.1 mg/ml) was added to inhibit vasospasm. Vascular pressures were referenced to the lung base. After a transient hydrostatic stress to maximize recruitment, vascular pressures were set at 5 cmH2O, and lungs were allowed to become isogravimetric (30-60 min). A fluid filtration coefficient (Kf) was determined by the use of a modification of the method of Drake and colleagues [Am. J. Physiol. 234 (Heart Circ. Physiol. 3): H266-H274, 1978]. EAV's were isolated by zoning techniques. In control preparations arterial and venous EAV's accounted for 26% (n = 9) and 38% (n = 11) of the total leakage, respectively. In all three models Kf increased two- to fourfold when the lungs were in zone 3 (alveolar vessels and arterial and venous EAV's contributing to the leakage).(ABSTRACT TRUNCATED AT 250 WORDS)     

Glycolysis is not required for fluid homeostasis in isolated rabbit lungs

We investigated whether glycolysis was necessary to maintain the integrity of vascular endothelial and alveolar epithelial barriers in continually weighed isolated rabbit lungs. Lungs were perfused with a cell-free buffered salt solution, and glycolysis was inhibited with a glucose analogue (alpha-methyl glucoside, alpha-MG) or one of two glycolysis inhibitors (iodoacetic acid, IAA, or NaF). Fluid filtration rates (FFR's, the change in lung weight/time) in response to a 7.5-min zone 3 hydrostatic stress (pulmonary arterial and venous pressures raised from 8 to 15 cmH2O, alveolar pressure kept constant at 4 cm on the deflation limb) were repeatedly measured for 120 min after which the lungs were lavaged. The total protein concentration was measured in the bronchoalveolar lavage fluid (BALP). Lactate production was measured to verify inhibition of glycolysis. Lower concentrations of IAA and alpha-MG eliminated lactate production but did not affect FFR or BALP. NaF also had no effect on the FFR or BALP. Only high concentrations of IAA increased FFR and BALP, seemingly by causing nonspecific membrane injury that was unrelated to its specific effects on glycolysis. The glycolytic pathway for energy production is not necessary to maintain the integrity of the pulmonary endothelial-epithelial barrier.     

Air interface and elastic recoil affect vascular resistance in three zones of rabbit lungs

We examined the effect of the air interface on pulmonary vascular resistance (PVR) in zones 1, 2, and 3 by comparing pressure-flow data of air- and liquid-filled isolated rabbit lungs. Lungs were perfused with Tyrode's solution osmotically balanced with 1% albumin and 4% dextran and containing the vasodilator papaverine (0.05 mg/ml). Lung volume was varied by negative pleural pressure form 0 to -25 cmH2O. Pulmonary artery (Ppa) and venous (Ppv) pressures were fixed at various levels relative to the lung base. Alveolar pressure (PA) was always zero, and perfusate flow was measured continuously. In zone 1 Ppa was -2.5 cmH2O and Ppv was -15 cmH2O. In zone 2 Ppa was 10 cmH2O and Ppv was -5 cmH2O. In zone 3 Ppa was 15 cmH2O and Ppv was 8 cmH2O. We found that in zone 1 the interface was essential for perfusion, but in zones 2 and 3 it had much lesser effects. In general, PVR depended almost uniquely (i.e., with small hysteresis) on transpulmonary pressure, whereas a large hysteresis existed between PVR and lung volume. PVR was high in collapsed and especially in atelectatic lungs, fell sharply with moderate inflation, and within the ranges of vascular pressure studied did not rise again toward total lung capacity. These results suggest that in zone 1 the interface maintains the patency of some alveolar vessels, probably in corners. The majority of alveolar septal vessels appears to be exposed directly to PA in zones 2 and 3, because at equal transpulmonary pressure the PVR is similar in the presence or absence of an interface.     

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.     

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)     

Flow characteristics of open vessels in zone 1 rabbit lungs

To describe the flow characteristics of vessels open in zone 1, we perfused isolated rabbit lungs with Tyrode's solution containing 1% albumin, 4% dextran, and papaverine (0.05 mg/ml). Lungs were expanded by negative pleural pressure (Ppl) of -10, -15, -20, and -25 cmH2O. Pulmonary arterial (Ppa) and venous (Ppv) pressures were varied relative to alveolar pressure (PA = 0) and measured 5-10 mm inside the pleura (i) and outside (o) of the lungs. With Ppa(o) at -2.5 cmH2O, we constructed pressure-flow (P-Q) curves at each Ppl by lowering Ppv(o) until Q reached a maximum, indicating fully developed zone 1 choke flow. Maximum flows were negligible until Ppl fell below -10 cmH2O, then increased rapidly at Ppl of -15 and -20 cmH2O, and at Ppl of -25 cmH2O reached about 15 ml.min-1.kg body wt-1. The Ppv(o) at which flow became nearly constant depended on degree of lung inflation and was 5-8 cmH2O more positive than Ppl. As Ppv(o) was lowered below Ppa(o), Ppv(i) remained equal to Ppv(o) until Ppv(i) became fixed at a pressure 2-3 cmH2O more positive than Ppl. At this point the choke flow was therefore located in veins near the pleural boundary. No evidence of choke flow (only ohmic resistance) was seen in the intrapulmonary segment of the vessels remaining open in zone 1. With Ppv(o) held roughly at Ppl, Q could be stopped by lowering Ppa(o), at which time Ppa(i) was several cmH2O above Ppv(i), showing that intrapulmonary vessel closure had occurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Indirect estimate of perimicrovascular pressure rise in edema in isolated zone 1 lung

To determine how liquid accumulation affects extra-alveolar perimicrovascular interstitial pressure, we measured filtration rate under zone 1 conditions (25 cmH2O alveolar pressure, 20 or 10 cmH2O vascular pressure) in isolated dog lung lobes in which all vessels were filled with autologous plasma. In the base-line condition, starting with normal extra-alveolar water content, filtration rate decreased by about one-half over 1 h as edema liquid slowly accumulated. We repeated each experiment after inducing edema (up to 100% lung weight gain). The absolute values and time course of filtration in the edema condition did not differ from base-line, i.e., the edema did not affect the time course of filtration. To compute the maximal initial and maximal change in extra-alveolar perimicrovascular pressure that occurred over each 1-h filtration study, we first assumed that the reflection coefficient is 0 in the Starling equation, then calculated perimicrovascular pressure and filtration coefficient from two equations with two unknowns. The mean filtration coefficient in 10 lobes is 0.063 g/(min X cmH2O X 100 g wet wt), and the initial perimicrovascular pressure is 3.9 cmH2O, rising by 4-7 cmH2O at 1 h. Finally we tested low protein perfusates and found the filtration rate was higher. We calculated an overall reflection coefficient = 0.44, a decrease in the initial perimicrovascular pressure to 1.9 cmH2O and a slightly lower increase after 1 h of edema formation, 2.2-6.6 cmH2O.     

Lymph flow from edematous dog lungs

We measured the flow rate (QLV) from cannulated lung lymph vessels in anesthetized dogs. Low-resistance lymph cannulas were used and the vessels were cannulated at the lung hilus. When we increased left atrial pressure to 42.9 +/- 5.7 (SD) cmH2O (base line = 6.6 +/- 4.6 cmH2O), the lungs became edematous and QLV increased from a base line of 20.4 +/- 21.5 microliters/min to 388 +/- 185 microliters/min. QLV plateaued at the higher level. We also measured the relationship between lymph flow rate and the height of the outflow end of the lymph cannula. From this relationship, determined at the end of the period of elevated left atrial pressure, we calculated the effective resistance and pressure driving lymph from the lungs. We also cannulated lymph vessels in the downstream direction and estimated the effective resistance and pressure opposing flow into the part of the lymphatic system between the lung hilus and the veins (extrapulmonary lymph vessels). We found that the effective resistance of the extrapulmonary part of the lymph system (0.042 +/- 0.030 (SD) cmH2O X min X microliter-1) was large compared with the resistance of the lymph vessels from the lungs (0.026 +/- 0.027). These data indicate that the resistance of the extrapulmonary part of the lung lymph system limits the maximum flow of lymph from edematous lungs.     

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.     

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.     

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.     

Mechanics of edematous lungs.

Using the parenchymal marker technique, we measured pressure (P)-volume (P-V) curves of regions with volumes of approximately 1 cm3 in the dependent caudal lobes of oleic acid-injured dog lungs, during a very slow inflation from P = 0 to P = 30 cmH2O. The regional P-V curves are strongly sigmoidal. Regional volume, as a fraction of volume at total lung capacity, remains constant at 0.4-0.5 for airway P values from 0 to approximately 20 cmH2O and then increases rapidly, but continuously, to 1 at P = approximately 25 cmH2O. A model of parenchymal mechanics was modified to include the effects of elevated surface tension and fluid in the alveolar spaces. P-V curves calculated from the model are similar to the measured P-V curves. At lower lung volumes, P increases rapidly with lung volume as the air-fluid interface penetrates the mouth of the alveolus. At a value of P = approximately 20 cmH2O, the air-fluid interface is inside the alveolus and the lung is compliant, like an air-filled lung with constant surface tension. We conclude that the properties of the P-V curve of edematous lungs, particularly the knee in the P-V curve, are the result of the mechanics of parenchyma with constant surface tension and partially fluid-filled alveoli, not the result of abrupt opening of airways or atelectatic parenchyma.     

Alveolar fluid reabsorption is impaired by increased left atrial pressures in rats

Cardiogenic pulmonary edema results from increased hydrostatic pressures across the pulmonary circulation. We studied active Na(+) transport and alveolar fluid reabsorption in isolated perfused rat lungs exposed to increasing levels of left atrial pressure (LAP; 0--20 cmH(2)O) for 60 min. Active Na(+) transport and fluid reabsorption did not change when LAP was increased to 5 and 10 cmH(2)O compared with that in the control group (0 cmH(2)O; 0.50 +/- 0.02 ml/h). However, alveolar fluid reabsorption decreased by approximately 50% in rat lungs in which the LAP was raised to 15 cmH(2)O (0.25 +/- 0.03 ml/h). The passive movement of small solutes ((22)Na(+) and [(3)H]mannitol) and large solutes (FITC-albumin) increased progressively in rats exposed to higher LAP. There was no significant edema in lungs with a LAP of 15 cmH(2)O when all active Na(+) transport was inhibited by hypothermia or amiloride (10(-4) M) and ouabain (5 x 10(-4) M). However, when LAP was increased to 20 cmH(2)O, there was a significant influx of fluid (-0.69 +/- 0.10 ml/h), precluding the ability to assess the rate of fluid reabsorption. In additional studies, LAP was decreased from 15 to 0 cmH(2)O in the second and third hours of the experimental protocol, which resulted in normalization of lung permeability to solutes and alveolar fluid reabsorption. These data suggest that in an increased LAP model, the changes in clearance and permeability are transient, reversible, and directly related to high pulmonary circulation pressures.     

Stress adaptation and low-frequency impedance of rat lungs

At transpulmonary pressures (Ptp) of 7-12 cmH2O, pressure-volume hysteresis of isolated cat lungs has been found to be 20-50% larger than predicted from their amount of stress adaptation (J. Hildebrandt, J. Appl. Physiol. 28: 365-372, 1970). This behavior is inconsistent with linear viscoelasticity and has been interpreted in terms of plastoelasticity. We have reinvestigated this phenomenon in isolated lungs from 12 Wistar rats by measuring 1) the changes in Ptp after 0.5-ml step volume changes (initial Ptp of 5 cmH2O) and 2) their response to sinusoidal pressure forcing from 0.01 to 0.67 Hz (2 cmH2O peak to peak, mean Ptp of 6 cmH2O). Stress adaptation curves were found to fit approximately Hildebrandt's logarithmic model [delta Ptp/delta V = A - B.log(t)] from 0.2 to 100 s, where delta V is the step volume change, A and B are coefficients, and t is time. A and B averaged 1.06 +/- 0.11 and 0.173 +/- 0.019 cmH2O/ml, respectively, with minor differences between stress relaxation and stress recovery curves. The response to sinusoidal forcing was characterized by the effective resistance (Re) and elastance (EL). Re decreased from 2.48 +/- 0.41 cmH2O.ml-1.s at 0.01 Hz to 0.18 +/- 0.03 cmH2O.ml-1.s at 0.5 Hz, and EL increased from 0.99 +/- 0.10 to 1.26 +/- 0.20 cmH2O/ml on the same frequency range. These data were analyzed with the frequency-domain version of the same model, complemented by a Newtonian resistance (R) to account for airway resistance: Re = R + B/ (9.2f) and EL = A + 0.25B + B . log 2 pi f, where f is the frequency.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alveolar air-tissue interface and nuclear magnetic resonance behavior of lung

Inflated lungs are characterized by a short nuclear magnetic resonance (NMR) free induction decay (rapid disappearance of NMR signal), likely due to internal (tissue-induced) magnetic field inhomogeneity produced by the alveolar air-tissue interface. This phenomenon can also be detected using temporally symmetric and asymmetric NMR spin-echo sequences; these sequences generate a pair of NMR images from which a difference signal (delta) is obtained (reflecting the signal from lung water experiencing the air-tissue interface effect). We measured delta in normal excised rat lungs at inflation pressures of 0-30 cmH2O for asymmetry times (a) of 1-6 ms. Delta was low in degassed lungs and increased markedly with alveolar opening when measured at a = 6 ms (delta 6 ms); delta 6 ms varied little during the rest of the inflation-deflation cycle. Delta 1 ms (a = 1 ms) did not vary significantly on inflation and deflation. Measurements of delta at a = 3 and 5 ms generally lay between those of delta 1 ms and delta 6 ms. These findings, which are consistent with theoretical predictions, suggest that measurements of delta at appropriate asymmetry times are particularly sensitive to alveolar opening and may provide a means of distinguishing alveolar recruitment from alveolar distension in the pressure-volume behavior of the lung.     

Heterogeneity of mean alveolar pressure during high-frequency oscillations

Mean alveolar pressure may exceed mean airway pressure during high-frequency oscillations (HFO). To assess the magnitude of this effect and its regional heterogeneity, we studied six excised dog lungs during HFO [frequency (f) 2-32 Hz; tidal volume (VT) 5-80 ml] at transpulmonary pressures (PL) of 6, 10, and 25 cmH2O. We measured mean pressure at the airway opening (Pao), trachea (Ptr), and four alveolar locations (PA) using alveolar capsules. Pao was measured at the oscillator pump, wherein the peak dynamic head was less than 0.2 cmH2O. Since the dynamic head was negligible here, and since these were excised lungs, Pao thus represented true applied transpulmonary pressure. Ptr increasingly underestimated Pao as f and VT increased, with Pao - Ptr approaching 8 cmH2O. PA (averaged over all locations) and Pao were nearly equal at all PL's, f's, and VT's, except at PL of 6, f 32 Hz, and VT 80 ml, where (PA - Pao) was 3 cmH2O. Remarkably, mean pressure in the base exceeded that in the apex increasingly as f and VT increased, the difference approaching 3 cmH2O at high f and VT. We conclude that, although global alveolar overdistension assessed by PA - Pao is small during HFO under these conditions, larger regional heterogeneity in PA's exists that may be a consequence of airway branching angle asymmetry and/or regional flow distribution.     

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.