Longitudinal distribution of vascular compliance in the canine lung

With an isolated perfused canine lung, the compliance of pulmonary circulation was measured and partitioned into components corresponding to alveolar and extra-alveolar compartments. When the lungs were in zone 3, changes in outflow pressure (delta Po) affected all portions of the vasculature causing a change in lung blood volume (delta V). Thus the ratio delta V/delta Po in zone 3 represented the compliance of the entire pulmonary circulation (Cp) plus that of the left atrium (Cla). When the lungs were in zone 2, changes in Po affected only the extra-alveolar vessels that were downstream from the site of critical closure in the alveolar vessels. Thus the ratio delta V/delta Po with forward flow in zone 2 represented the compliance of the venous extra-alveolar vessels (Cv) plus Cla. With reverse flow in zone 2, delta V/delta Po represented the compliance of the arterial extra-alveolar vessels (Ca). The compliance of the alveolar compartment (Calv) was calculated from the difference between Cp and the sum of Ca + Cv. When Po was 6-11 mmHg, Cp was 0.393 +/- 0.0380 (SE) ml X mmHg-1 X kg-1 with forward perfusion and 0.263 +/- 0.0206 (SE) ml X mmHg-1 X kg-1 with reverse perfusion. Calv was 79 and 68% of Cp with forward and reverse perfusion, respectively. When Po was raised to 16-21 mmHg, Cp decreased to 0.225 +/- 0.0235 (SE) ml X mmHg-1 X kg-1 and 0.183 +/- 0.0133 (SE) ml X mmHg-1 X kg-1 with forward and reverse perfusion, respectively. Calv also decreased but remained the largest contributor to Cp. We conclude that the major site of pulmonary vascular compliance in the canine lung is the alveolar compartment, with minor contributions from the arterial and venous extra-alveolar segments.     

Locus of hypoxic vasoconstriction in isolated ferret lungs

To determine whether hypoxic pulmonary vasoconstriction (HPV) occurs mainly in alveolar or extra-alveolar vessels in ferrets, we used two groups of isolated lungs perfused with autologous blood and a constant left atrial pressure (-5 Torr). In the first group, flow (Q) was held constant at 50, 100, and 150 ml.kg-1 X min-1, and changes in pulmonary arterial pressure (Ppa) were recorded as alveolar pressure (Palv) was lowered from 25 to 0 Torr during control [inspired partial pressure of O2 (PIO2) = 200 Torr] and hypoxic (PIO2 = 25 Torr) conditions. From these data, pressure-flow relationships were constructed at several levels of Palv. In the control state, lung inflation did not affect the slope of the pressure-flow relationships (delta Ppa/delta Q), but caused the extrapolated pressure-axis intercept (Ppa0), representing the mean backpressure to flow, to increase when Palv was greater than or equal to 5 Torr. Hypoxia increased delta Ppa/delta Q and Ppa0 at all levels of Palv. In contrast to its effects under control condition, lung inflation during hypoxia caused a progressive decrease in delta Ppa/delta Q, and did not alter Ppa0 until Palv was greater than or equal to 10 Torr. In the second group of experiments flow was maintained at 100 ml.kg-1 X min-1, and changes in lung blood volume (LBV) were recorded as Palv was varied between 20 and 0 Torr. In the control state, inflation increased LBV over the entire range of Palv. In the hypoxic state inflation decreased LBV until Palv reached 8 Torr; at Palv 8-20 Torr, inflation increased LBV.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Hydraulic conductance of lung endothelial phenotypes and Starling safety factors against edema

Recent permeability studies comparing endothelial cell phenotypes derived from alveolar and extra-alveolar vessels have significant implications for interpreting the mechanisms of fluid homeostasis in the intact lung. These studies indicate that confluent monolayers of rat pulmonary microvascular endothelial cells had a hydraulic conductance (L(p)) that was only 5% and a transendothelial flux rate for 72-kDa dextran only 9% of values determined for rat pulmonary artery endothelial cell monolayers. On the basis of previous studies partitioning the filtration coefficients between alveolar and extra-alveolar vascular segments in rat lungs and previous studies of lymph albumin fluxes and permeability, the contribution of the alveolar capillary segment to total albumin flux in lymph was estimated to be less than 10%. In addition, the Starling safety factors against the edema calculated for the alveolar capillaries are quite different from those estimated for whole lung. Estimates of the edema safety factor due to increased filtration across the alveolar capillary wall based on the low L(p) indicate it is quantitatively the greatest safety factor, although it would be a minor safety factor for extra-alveolar vessels. Also, a markedly higher effective protein osmotic absorptive force for plasma proteins must occur in the capillaries relative to extra-alveolar vessels. The lower L(p) for alveolar capillaries also has implications for the sequence of hydrostatic edema formation, and it also may have a role in preventing exercise-induced alveolar flooding.     

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.     

Influence of vascular distending pressure on regional flows in isolated perfused dog lungs

To confirm the regional differences in vascular pressure vs. flow properties of lung regions that have been documented in zone 2 conditions [pulmonary venous pressure (Ppv) less than alveolar pressure], regional distending pressure vs. flow curves in zone 3 were generated by use of isolated blood-perfused dog lungs (3 right and 5 left lungs). Each lung was kept inflated at constant inflation pressure (approximately 50% of full inflation volume) while radioactively labeled microspheres were injected at different settings of Ppv. To achieve maximal vascular distension, Ppv was increased to approximately 30 cmH2O above alveolar pressure for the first injection. Subsequent injections were made at successively lower Ppv's. The difference between pulmonary arterial pressure and Ppv was kept constant for all injections. As was found in zone 2 conditions, there were differences in the regional distending pressure vs. flow curves among lung regions. To document the regional variability in the curves, the distribution of flow at a regional Ppv of 30 cmH2O above alveolar pressure was analyzed. There was a statistically significant linear gradient in this flow distribution from dorsal to ventral regions of the lungs but no consistent gradient in the caudad to cephalad direction. These results indicate that, even in near-maximally distended vessels, the dorsal regions of isolated perfused dog lungs have lower intrinsic vascular resistance compared with ventral regions.     

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.     

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)     

Effects of lung volume and alveolar surface tension on pulmonary vascular resistance

Utilizing the arterial and venous occlusion technique, the effects of lung inflation and deflation on the resistance of alveolar and extraalveolar vessels were measured in the dog in an isolated left lower lobe preparation. The lobe was inflated and deflated slowly (45 s) at constant speed. Two volumes at equal alveolar pressure (Palv = 9.9 +/- 0.6 mmHg) and two pressures (13.8 +/- 0.8 mmHg, inflation; 4.8 +/- 0.5 mmHg, deflation) at equal volumes during inflation and deflation were studied. The total vascular pressure drop was divided into three segments: arterial (delta Pa), middle (delta Pm), and venous (delta Pv). During inflation and deflation the changes in pulmonary arterial pressure were primarily due to changes in the resistance of the alveolar vessels. At equal Palv (9.9 mmHg), delta Pm was 10.3 +/- 1.2 mmHg during deflation compared with 6.8 +/- 1.1 mmHg during inflation. At equal lung volume, delta Pm was 10.2 +/- 1.5 mmHg during inflation (Palv = 13.8 mmHg) and 5.0 +/- 0.7 mmHg during deflation (Palv = 4.8 mmHg). These measurements suggest that the alveolar pressure was transmitted more effectively to the alveolar vessels during deflation due to a lower alveolar surface tension. It was estimated that at midlung volume, the perimicrovascular pressure was 3.5-3.8 mmHg greater during deflation than during inflation.     

Three-dimensional reconstruction of alveoli in the rat lung for pressure-volume relationships

To determine alveolar pressure-volume relationships, alveolar three-dimensional reconstructions were prepared from lungs fixed by vascular perfusion at various points on the pressure-volume curve. Lungs from male Sprague-Dawley rats were fixed by perfusion through the pulmonary artery following a pressure-volume maneuver to the desired pressure point on either the inflation or deflation curve. Tissue samples from lungs were serially sectioned for determination of the volume fraction of alveoli and alveolar ducts and reconstruction of alveoli. Alveoli from lungs fixed at 5 cmH2O on the deflation curve (approximating functional residual volume) had a volume of 173 X 10(3) microns3, a surface area of 11,529 microns2, a mouth opening diameter of 72.7 microns, and a mean caliper diameter of 91.8 micron (SE). Alveolar shape changes during deflation from total lung capacity to residual volume was first (30 to 10 cmH2O) associated with little change in the diameter of the alveoli (102.7 +/- 2.4 to 100.3 +/- 3.3 microns). In the range overlapping normal breathing (10 to 0 cmH2O) there was a substantial decrease in diameter (100.3 +/- 3.3 to 43.3 +/- 2.3 microns). These measurements and others made on the relative changes in the dimensions of the alveolus suggest that the elastic network, particularly around the alveolar ducts, are predominant in determining lung behavior near the volume expansion limits of the lung while the elastic and surface tension properties of the alveoli are predominant in the volume range around functional residual capacity.     

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.     

Influence of lung volume and left atrial pressure on reverse pulmonary venous blood flow

Infarction of the lung is uncommon even when both the pulmonary and the bronchial blood supplies are interrupted. We studied the possibility that a tidal reverse pulmonary venous flow is driven by the alternating distension and compression of alveolar and extra-alveolar vessels with the lung volume changes of breathing and also that a pulsatile reverse flow is caused by left atrial pressure transients. We infused SF6, a relatively insoluble inert gas, into the left atrium of anesthetized goats in which we had interrupted the left pulmonary artery and the bronchial circulation. SF6 was measured in the left lung exhalate as a reflection of the reverse pulmonary venous flow. No SF6 was exhaled when the pulmonary veins were occluded. SF6 was exhaled in increasing amounts as left atrial pressure, tidal volume, and ventilatory rates rose during mechanical ventilation. SF6 was not excreted when we increased left atrial pressure transients by causing mitral insufficiency in the absence of lung volume changes (continuous flow ventilation). Markers injected into the left atrial blood reached the alveolar capillaries. We conclude that reverse pulmonary venous flow is driven by tidal ventilation but not by left atrial pressure transients. It reaches the alveoli and could nourish the alveolar tissues when there is no inflow of arterial blood.     

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.     

Flow through zone 1 lungs utilizes alveolar corner vessels

We have previously observed flows equivalent to 15% of the resting cardiac output of rabbits occurring through isolated lungs that were completely in zone 1. To distinguish between alveolar corner vessels and alveolar septal vessels as a possible zone 1 pathway, we made in vivo microscopic observations of the subpleural alveolar capillaries in five anesthetized dogs. Videomicroscopic recordings were made via a transparent thoracic window with the animal in the right lateral position. From recordings of the uppermost surface of the left lung, alveolar septal and corner vessels were classified depending on whether they were located within or between alveoli, respectively. Observations were made with various levels of positive end-expiratory pressure (PEEP) applied only to the left lung via a double-lumen endotracheal tube. Consistent with convention, flow through septal vessels stopped when PEEP was raised to the mean pulmonary arterial pressure (the zone 1-zone 2 border). However, flow through alveolar corner vessels continued until PEEP was 8-16 cmH2O greater than mean pulmonary arterial pressure (8-16 cm into zone 1). These direct observations support the idea that alveolar corner vessels rather than patent septal vessels provide the pathway for blood flow under zone 1 conditions.     

Hemoglobin and red blood cells alter the response of expired nitric oxide to mechanical forces

Expired nitric oxide (NO(e)) varies with hemodynamic or ventilatory perturbations, possibly due to shear stress- or stretch-stimulated NO production. Since hemoglobin (Hb) binds NO, NO(e) changes may reflect changes in blood volume and flow. To determine the role of blood and mechanical forces, we measured NO(e) in anesthetized rabbits, as well as rabbit lungs perfused with buffer, red blood cells (RBCs) or Hb following changes in flow, venous pressure (P(v)), and positive end-expiratory pressure (PEEP). In buffer-perfused lungs decreases in flow and P(v) reduced NO(e), but NO(e) rose when RBCs and Hb were present. These findings are consistent with changes in vascular NO production, whose detection is obscured in blood-perfused lungs by the more dominant effect of Hb NO scavenging. PEEP decreased NO(e) in all perfused lungs but increased NO(e) in live rabbits. The NO(e) fall with PEEP in isolated lungs is consistent with flow redistribution from alveolar septal capillaries to extra-alveolar vessels and decreased surface area or a direct, stretch-mediated depression of lung epithelial NO production. In live rabbits, increased NO(e) may reflect blood flow reduction and decreased Hb NO scavenging and/or autonomic responses that increase NO production. We conclude that blood and systemic responses render it difficult to use NO(e) changes as an accurate measure of lung tissue NO production.     

Micropuncture pressure in small arteries or veins of perfused rabbit lungs

Until now, direct micropuncture measurements of vascular pressure in lung have been limited to small vessels less than 100 microns on the pleural surface. On the other hand, direct pressure measurements using small catheters (less than 1-mm OD) in pulmonary vessels have been limited to those greater than 1.2 mm. We measured pressure in intermediate-sized microvessels (300-700 microns) using the micropuncture method in isolated perfused rabbit lungs. These microvessels are located 2 or 3 mm beneath the pleura. We exposed them by microsurgery and punctured the relatively thick-walled vessels with specially configured micropipettes. We exposed one pulmonary microvessel in each rabbit lung by microsurgery on the left middle lobe. In 15 rabbit lungs we measured pressure in a total of six small arteries (275- to 470-microns diam) and nine small veins (300- to 700-microns diam) under high zone 3 conditions, near the zone 2/3 boundary. We found approximately 35% of the total pulmonary vascular pressure drop in arteries greater than 275-microns diam and 7% in veins greater than 300-microns diam. In veins greater than 500-microns diam, there was no measurable pressure drop. After the measurements, we froze the lung and confirmed that there was no detectable interstitial or alveolar edema in the cross sections of the punctured site. Our data are compatible with those of other investigators who have used isolated perfused rabbit lungs under similar experimental conditions.     

Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation.

Pulmonary microvascular and alveolar epithelial permeability were evaluated in vivo by scintigraphic imaging during lung distension. A zone of alveolar flooding was made by instilling a solution containing 99mTc-albumin in a bronchus. Alveolar epithelial permeability was estimated from the rate at which this tracer left the lungs. Microvascular permeability was simultaneously estimated measuring the accumulation of (111)In-transferrin in lungs. Four levels of lung distension (corresponding to 15, 20, 25, and 30 cmH2O end-inspiratory airway pressure) were studied during mechanical ventilation. Computed tomography scans showed that the zone of alveolar flooding underwent the same distension as the contralateral lung during inflation with gas. Increasing lung tissue stretch by ventilation at high airway pressure immediately increased microvascular, but also alveolar epithelial, permeability to proteins. The same end-inspiratory pressure threshold (between 20 and 25 cmH2O) was observed for epithelial and endothelial permeability changes, which corresponded to a tidal volume between 13.7 +/- 4.69 and 22.2 +/- 2.12 ml/kg body wt. Whereas protein flux from plasma to alveolar space ((111)In-transferrin lung-to-heart ratio slope) was constant over 120 min, the rate at which 99mTc-albumin left air spaces decreased with time. This pattern can be explained by changes in alveolar permeability with time or by a compartment model including an intermediate interstitial space.     

Alveolar vessel behavior in the zone 2 lung inferred from indicator-dilution data

To gain insight into the changes occurring in alveolar vessels when alveolar pressure exceeds venous pressure at the downstream end of the alveolar vessels (zone 2), we compared the uptake of serotonin and the extravascular volume accessible to 3HOH (Qev) under zone 2 and 3 conditions in isolated dog lung lobes. We also examined the influence of occluding some of the small pulmonary arteries with 58- to 548-micron-diam beads on the serotonin uptake and Qev. We found that, with the bead embolization, both the serotonin uptake and the Qev were reduced, whereas the change from zone 3 to 2 reduced serotonin uptake but did not change Qev. A plausible explanation for these observations is that the beads occluded vessels that were relatively large compared with those in which significant transvascular 3HOH exchange and serotonin uptake take place. Perfusion ceased in the collection of capillaries normally served by the obstructed arteries. Thus the extravascular water and the serotonin uptake sites downstream from the obstructions were not accessible to the indicators during the short time interval of the indicator passage through the lung. On the other hand, the change from zone 3 to zone 2 resulted in the collapse of small individual capillary segments within the alveolar vessel bed. Since the serotonin does not readily diffuse from the vessels through the tissue, it could not reach the endothelial cells of the collapsed capillaries. However, since the distances for diffusion between collapsed capillaries and neighboring perfused capillaries were small, the more highly diffusible 3HOH had access to the same Qev under both zone 2 and 3 conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in strength of lung inflation reflex during prolonged inflation.

Recovery from respiratory inhibition produced by the lung inflation reflex was studied in anesthetized dogs, paralyzed and ventilated with a respiratory pump. During constant ventilation the lungs were periodically inflated using positive end-expiratory pressure, while the respiratory motor output was monitored in the phrenic nerve. Inhibition of the phrenic discharge was followed by gradual recovery throughout 8-min inflation periods despite constant blood gases. Recording afferent potentials in a vagus nerve indicated that adaptation of pulmonary stretch receptors contributed to the initial recovery of the phrenic discharge, but this recovery continued after the receptor discharge had stabilized. The phrenic discharge also recovered after initial inhibition in two situations which avoided stretch receptor adaptation: a) when the stretch receptor discharge from the separate lungs was alternated in an overlapping manner by asynchronous pulmonary ventilation, and b) during continuous electrical stimulation of a vagus nerve. Phrenic activity was temporarily increased above its control value after periods of lung inflation, asynchronous ventilation and vagal stimulation. It is concluded that the lung inflation reflex gradually attenuates during prolonged stimulation due to both stretch receptor adaptation and changes within the central pathways.