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.     

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.     

Influence of lung volume and alveolar pressure on reverse pulmonary venous blood flow.

We have reported that left atrial blood refluxes through the pulmonary veins to gas-exchanging tissue after pulmonary artery ligation. This reverse pulmonary venous flow (Qrpv) was observed only when lung volume was changed by ventilation. This was believed to drive Qrpv by alternately distending and compressing the alveolar and extra-alveolar vessels. Because lung and pulmonary vascular compliances change with lung volume, we studied the effect of positive end-expiratory pressure (PEEP) on the magnitude of Qrpv during constant-volume ventilation. In prone anesthetized goats (n = 8), using the right lung to maintain normal blood gases, we ligated the pulmonary and bronchial arterial inflow to the left lung and ventilated each lung separately. A solution of SF6, an inert gas, was infused into the left atrium. SF6 clearance from the left lung was determined by the Fick principle at 0, 5, 10, and 15 and again at 0 cmH2O PEEP and was used to measure Qrpv. Left atrial pressure remained nearly constant at 20 cmH2O because the increasing levels of PEEP were applied to the left lung only. Qrpv was three- to fourfold greater at 10 and 15 than at 0 cmH2O PEEP. At these higher levels of PEEP, there were greater excursions in alveolar pressure for the same ventilatory volume. We believe that larger excursions in transpulmonary pressure during tidal ventilation at higher levels of PEEP, which compressed alveolar vessels, resulted in the reflux of greater volumes of left atrial blood, through relatively noncompliant extra-alveolar veins into alveolar corner vessels, and more compliant extra-alveolar arteries.     

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.     

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.     

Vascular segmental permeabilities at high peak inflation pressure in isolated rat lungs

The response of segmental filtration coefficients (Kf) to high peak inflation pressure (PIP) injury was determined in isolated perfused rat lungs. Total (K f,t ), arterial (K f,a ), and venous (K f,v ) filtration coefficients were measured under baseline conditions and after ventilation with 40-45 cmH(2)O PIP. K f,a and K f,v were measured under zone I conditions by increasing airway pressure to 25-27 cmH(2)O. The microvascular segment K f (K f,mv ) was then calculated by: K f,mv = K f,t - K f,a - K f,v. The baseline K f,t was 0.090 +/- 0.022 ml. min(-1). cm H2O(-1). 100 g(-1) and segmentally distributed 18% arterial, 41% venous, and 41% microvascular. After high PIP injury, K f,t increased by 680%, whereas K f,a, K f,v, and K f,mv increased by 398, 589, and 975%, respectively. Pretreatment with 50 microM gadolinium chloride prevented the high PIP-induced increase in K f in all vascular segments. These data imply a lower hydraulic conductance for microvascular endothelium due to its large surface area and a gadolinium-sensitive high-PIP injury, produced in both alveolar and extra-alveolar vessel segments.     

Effect of lung inflation on fluid flux in zone 1 lungs

Because of conflicting data in the literature, we studied the effect of positive-pressure inflation on transvascular fluid filtration in zone 1 lungs. Lungs from New Zealand White rabbits (n = 10) were excised, perfused with saline and autologous whole blood (1:1), ventilated, and continuously weighed. Pulmonary arterial and venous pressures (Pvas) were referenced to the most dependent part of the lung. A change in vascular volume (delta Vvas) and a fluid filtration rate (FFR) were calculated from the change in lung weight that occurred from 0 to 30 s and from 3 to 5 and 5 to 10 min, respectively, after changing alveolar pressure (PA). FFR's and delta Vvas's were measured with Pvas equal to 2 or 10 cmH2O and PA changing from 15 to 30 cmH2O when the lungs were normal and after they were made edematous. When Pvas = 2 cmH2O, increasing PA increased the Vvas and the FFR in both normal and edematous lungs. However, when Pvas = 10 cmH2O, increasing PA only slightly changed the Vvas and reduced the FFR in the normal lungs, and decreased Vvas and markedly decreased the FFR in the presence of edema. Inflating zone 1 lungs by positive pressure has an effect on transvascular fluid flux that depends on the Pvas. The results suggest that the sites of leakage in zone 1 also vary depending on Pvas and PA.     

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.     

Lung microvascular pressure profile measured by micropuncture in anesthetized dogs

We have micropunctured the lung in the open thorax of 17 anesthetized dogs to measure microvascular pressure. After intravenous pentobarbital sodium (25 mg/kg), we exposed the left lung through a wide left thoracotomy, which required rib excision. Through a double-lumen endotracheal tube, we ventilated the right lung to maintain normal blood gases and pH while we held the left lung motionless at an inflation pressure of 5 cmH2O. To reduce motion on the surface of the left lower lobe, we resected the left upper lobe, placed a Plexiglas baffle between the lobe and the heart, and held the lobe surface in a suction ring. In accordance with procedures we have previously described, we micropunctured subpleural vessels to measure microvascular pressure. At base line when alveolar pressure exceeded left atrial pressure (zone 2 conditions), 21, 38, and 41% of the total pressure drop occurred, respectively, in the arterial, microvascular, and venous segments. When we raised left atrial pressure above alveolar pressure (zone 3 conditions), the corresponding pressure drops were 30, 55, and 20% of total. The blood flow in the superficial layer of the lung averaged 15% less than the flow in the deeper layers as measured by distribution of 99mTc-albumin macroaggregates. We conclude that the intact and the isolated lung preparations in dog exhibit similar distributions of subpleural microvascular pressure.     

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.     

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)     

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.     

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.     

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)     

Effect of lung inflation on lung blood volume and pulmonary venous flow

Phasic changes in lung blood volume (LBV) during the respiratory cycle may play an important role in the genesis of the respiratory wave in arterial pressure, or pulsus paradoxus. To better understand the effects of lung inflation on LBV, we studied the effect of changes in transpulmonary pressure (delta Ptp) on pulmonary venous flow (Qv) in eight isolated canine lungs with constant inflow. Inflation when the zone 2 condition was predominant resulted in transient decreases in Qv associated with increases in LBV. In contrast, inflation when the zone 3 condition was predominant resulted in transient increases in Qv associated with decreases in LBV. These findings are consistent with a model of the pulmonary vasculature that consists of alveolar and extra-alveolar vessels. Blood may be expelled from alveolar vessels but is retained in extra-alveolar vessels with each inflation. The net effect on LBV and thus on Qv is dependent on the zone conditions that predominate during inflation, with alveolar or extra-alveolar effects being greater when the zone 3 or zone 2 conditions predominate, respectively. Lung inflation may therefore result in either transiently augmented or diminished Qv. Phasic changes in left ventricular preload may therefore depend on the zone conditions of the lungs during the respiratory cycle. This may be an important modulator of respiratory variations in cardiac output and blood pressure.     

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)     

Effect of zonal conditions and posture on pulmonary blood flow distribution to subpleural and interior lung.

Observations made on vessels seen directly beneath the pleura may not accurately reflect what occurs in vessels located deeper in the interior of the lung. We quantified flow to subpleural and deeper, interior regions under zone 1 or 2 conditions in excised (n = 5) and in vivo (n = 6) rabbit lungs, in the head-up or inverted position. After infusion of radiolabeled microspheres, lungs were dried at alveolar pressure of 25 cmH(2)O and sliced in 1-cm sections along the gravitational plane and in three planes in the dorsal-ventral axis. Regions located <1 mm from the pleural surface were dissected away from the remaining tissue. In both zonal conditions, 1) weight-normalized flow to the interior exceeded that found in subpleural regions; and 2) flow followed the gravitational gradient, with the correlation varying with the scale of measurement. We conclude that flow through subpleural vessels is less than that which occurs deeper in the interior, but the regional distributions of flow and the effects of zonal conditions are similar in the two regions.     

Hypoxia and angiotensin II infusion redistribute lung blood flow in lambs

To assess the effects of alveolar hypoxia and angiotensin II infusion on distribution of blood flow to the lung we performed perfusion lung scans on anesthetized mechanically ventilated lambs. Scans were obtained by injecting 1-2 mCi of technetium-labeled albumin macroaggregates as the lambs were ventilated with air, with 10-14% O2 in N2, or with air while receiving angiotensin II intravenously. We found that both alveolar hypoxia and infusion of angiotensin II increased pulmonary vascular resistance and redistributed blood flow from the mid and lower lung regions towards the upper posterior region of the lung. We assessed the effects of angiotensin II infusion on filtration pressure in six lambs by measuring the rate of lung lymph flow and the protein concentration of samples of lung lymph. We found that angiotensin II infusion increased pulmonary arterial pressure 50%, lung lymph flow 90%, and decreased the concentration of protein in lymph relative to plasma. These results are identical to those seen when filtration pressure increases during alveolar hypoxia. We conclude that alveolar hypoxia and angiotensin II infusion both increase fluid filtration in the lung by increasing filtration pressure. The increase in filtration pressure may be the result of a redistribution of blood flow in the lung with relative overperfusion of vessels in some areas and transmission of the elevated pulmonary arterial pressure to fluid-exchanging sites in those vessels.