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Oxygenation improves in patients with adult respiratory distress syndrome and in animals with oleic acid-induced lung injury when they are turned from the supine to the prone position. Dependent and nondependent pleural pressures (Ppl) were measured in six pigs ventilated in the supine and prone positions before and after volume infusion (VI). Before VI the mean +/- SEM AaPO2 difference was 26 +/- 8 mm Hg when the animals were supine and 10 +/- 2 mm Hg when they were prone (p > 0.05). After VI the AaPO2 was 64 +/- 6 mm Hg when the animals were supine (p < 0.05) and 43 +/- 7 mm Hg when they were prone (p < 0.05). VI increased the Ppl gradient from 0.53 +/- 0.1 to 0.71 +/- 0.1 cm H2O/cm when the animals were supine (p < 0.05) and from 0.17 +/- 0.1 to 0.27 +/- 0.1 cm H2O/cm when they were prone (p < 0.05). Dependent Ppl at FRC was much less positive when the animals were prone versus supine (0.9 +/- 0.3 versus 3.0 +/- 0.5 cm H2O, p < 0.05), suggesting that the airways in these dependent regions would narrow and/or close and that ventilation to these regions would diminish as a result of VI.

Unilateral pulmonary artery obstruction (PAO) for 24–48 h, followed by reperfusion, results in pulmonary edema and lung inflammation. We hypothesized that lung injury actually occurred during the period of PAO but, because of low microvascular pressures during the period of occlusion, was not detected until perfusion was reestablished. To test this hypothesis, we studied 14 rabbits divided into three groups: group I rabbits underwent sham occlusion of the left pulmonary artery for 24 h; group II rabbits underwent PAO but were not reperfused; and group III rabbits were subjected to PAO and then reperfused for 4 h. The fluid filtration coefficient measured during a zone 3 no-flow hydrostatic stress (pulmonary arterial pressure = pulmonary venous pressure, both greater than alveolar pressure) in group I lungs was less than that of lungs in either group II or III [0.52 +/- 0.02 (SE) ml.min-1.cmH2O.100 g wet wt-1 vs. 0.94 +/- 0.11 and 0.86 +/- 0.13 for groups II and III, respectively, P less than 0.05]. The wet-to-dry weight ratio of the left lung measured after the zone 3 stress was applied for 20 min was 6.90 +/- 0.09 in group I rabbits and 9.21 +/- 0.75 and 11.75 +/- 0.44 in groups II and III, respectively (P less than 0.05). Radiolabeled microspheres demonstrated that flow to the left lung was diminished after the period of PAO (38 +/- 4, 9 +/- 5, and 2 +/- 1% of cardiac output in groups I, II, and III, respectively; P less than 0.05 for group I vs. groups II and III).(ABSTRACT TRUNCATED AT 250 WORDS)

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)

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)

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.

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.

Leukotrienes (LTs) C4 and D4 are vasoconstrictors and are thought to increase both systemic and pulmonary vascular permeability. However, we and others have observed that LTC4 and LTD4 cause pulmonary vasoconstriction but do not increase the fluid filtration coefficient of excised guinea pig lungs perfused with a cell-depleted perfusate. To determine what vascular segments were exposed to an LT-induced increase in intravascular hydrostatic pressure we measured pulmonary arterial (Ppa), pulmonary arterial occlusion (Po,a), venous (Po,v) and double occlusion (Pdo) pressures in isolated guinea pig lungs perfused with a cell-depleted buffered salt solution before and after injecting 4 micrograms of LTB4, LTC4, or LTD4 into the pulmonary artery. All three LTs increased airway pressures and also increased Ppa, Po,a, and Pdo. Histamine (15 micrograms) as well as serotonin (20 or 200 micrograms) had the same effect. In excised rabbit lungs, histamine and serotonin increased only Ppa, and Po,a. LTC4 had no vasoactivity. There are marked species variations with regard to the activity and site of action of histamine, serotonin, and LTC4 on the pulmonary circulation.