Vascular pressure effects on lung edema formation after glass bead embolism

The canine lung lobe was embolized with 100-micron glass beads before lobectomy and blood anticoagulation. The lobe was isolated, ventilated, and pump-perfused with blood at an arterial pressure (Pa) of about 50 (high pressure, HP, n = 9) or 25 Torr (low pressure, LP, n = 9). Rus/PVR, the ratio of upstream (Rus) to total lobar vascular resistance (PVR), was determined by venous occlusion and the isogravimetric capillary pressure technique. The capillary filtration coefficient (Kf), an index of vascular permeability, was obtained from rate of lobe weight gain during stepwise capillary pressure (Pc) elevation. The embolized lobes became more edematous than nonembolized controls, (C, n = 11), (P less than 0.05), with Kf values of 0.20 +/- 0.04, 0.25 +/- 0.06, and 0.07 +/- 0.01 ml X min-1 X Torr-1 X 100 X g-1 in LP, HP, and C, respectively (P less than 0.05). The greater Rus/PVR in embolized lobes (P less than 0.05) protected the microvessels and, although Pc was greater in HP than in controls (P less than 0.05), Pc did not differ between HP and LP (P greater than 0.05). Although indexes of permeability did not differ between embolized groups (P greater than 0.05), HP became more edematous than LP (P less than 0.05). The greater edema in HP did not appear due to a greater imbalance of Starling forces across the microvessel wall or to vascular recruitment. At constant Pc and venous pressure, elevating Pa from 25 to 50 Torr in embolized lobes resulted in greater edema to suggest fluid filtration from precapillary vessels.     

Filtration coefficient obtained by stepwise pressure elevation in isolated dog lung

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

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

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

Effect of elevated vascular pressure transients on protein permeability in the lung

Neurogenic pulmonary edema (NPE) may develop in individuals with head trauma or seizures and is generally thought to have a hydrostatic basis in the severe degree of pulmonary hypertension that occurs. Recently, it has been suggested that vascular pressures may rise to levels that damage the vessels, leaving the patient at risk for further edema development. The objective of this study was to determine if pulmonary vascular protein permeability is increased in a canine isolated perfused left lower lung lobe (LLL) preparation by pressure transients that may occur in NPE. Venous pressure (Pv) was transiently raised to values ranging from 8 to 102 Torr in 19 LLL. One Pv transient was studied per LLL. After Pv was returned to normal, the osmotic reflection coefficient (sigma d) for total proteins was determined by the hematocrit-protein double indicator technique. No reduction in sigma d was observed until microvascular pressure exceeded 70 Torr. The average sigma d for the 11 LLL in which the peak microvascular pressure was less than 70 Torr was 0.74 +/- 0.03 (SE). Above this level sigma d fell linearly with increasing Pv, with a value of 0.26 being observed after the highest Pv transient. These results suggest that protein permeability may increase in patients with NPE who develop very large increases in pulmonary vascular pressures but may not be a universal occurrence in this disorder.     

Relationship of fluid filtration to lung vascular pressure during edema

Effect of edema on the relationship between rate of fluid filtration and vascular pressure was studied in ventilated isolated dog lung lobes blood-perfused at constant flow. Constant rate of lobe weight gain (S), representing transvascular fluid flux, was obtained at different venous pressures (Pv) as Pv was increased stepwise from 2 to 40 and then similarly decreased from 40 to 2 Torr (n = 6). In another group (n = 6), edema was maximized by reversing the sequence of Pv change; S was obtained during similar Pv steps as Pv was decreased from 40 to 2 and then returned to 40 Torr. In both groups, delta S was disproportionately greater for delta Pv at higher Pv's, with S vs. Pv fit by an exponential curve (P less than 0.001). The exponential relationship was independent of lung hydration inasmuch as greater edema on the second limb of Pv change did not alter the curve (P greater than 0.05). At 144% weight gain, interstitial compliance was 55.5 +/- 26.8 ml.100 g-1.Torr-1 (n = 10). Interstitial pressure reportedly remains constant, i.e., fails to increase to further buffer fluid filtration, after transition of the lung interstitium from low to high compliance at approximately 40% lung weight gain. If so, then the exponential S vs. Pv relationship observed in the present study at elevated interstitial compliance does not appear related to tissue pressure-buffering effects.     

Effect of hemolysis on reflection coefficient determined by endogenous blood indicators

The osmotic reflection coefficient (sigma) can be estimated from the increases in hematocrit and plasma protein concentration that result from fluid filtration occurring in an isolated perfused organ. We determined what effect perfusion pump-induced hemolysis has on the value of sigma determined by this technique in both the isolated canine left lower lung lobe (LLL) and forelimb by comparing estimates of sigma obtained before and after correction for hemolysis. Hemolysis was corrected by using the slopes of the relationships between hematocrit and plasma hemoglobin concentration and between the plasma protein and hemoglobin concentrations to correct hematocrit and protein concentration to a state of zero hemolysis. Uncorrected estimates of sigma in the LLL were 1.19 +/- 0.14 (SE) at a venous pressure (Pv) of 12 Torr (n = 7) and 0.90 +/- 0.02 at a Pv of 19 Torr (n = 6). Both sets of LLL's yielded sigma values of 0.77 +/- 0.03 after hemolysis correction. In the forelimb (n = 5), uncorrected and corrected estimates of sigma of 0.99 +/- 0.03 and 0.85 +/- 0.01, respectively, were obtained. The latter values were similar to sigma's (0.88 +/- 0.01) determined by lymph analysis in five additional forelimbs. We conclude that hemolysis results in overestimates of sigma. After hemolysis correction, this technique yields similar results to those obtained from lymph analysis for the forelimb and from published values for the LLL.     

Pulmonary vascular reactivity and permeability to alveolar hypoxia in the dog

Hemodynamics and vascular permeability were studied during acute alveolar hypoxia in isolated canine lung lobes perfused at constant flow with autogenous blood. Hypoxia was induced in the presence (COI + Hypox, n = 6) or absence (Hypox, n = 6) of cyclooxygenase inhibition (COI) with indomethacin or meclofenamate. Hypoxic ventilation reduced blood PO2 from 143 to 25-29 Torr without a change in PCO2. During hypoxia a capillary filtration coefficient (Kf) was obtained gravimetrically as an index of vascular permeability to water. In COI + Hypox, pulmonary arterial pressure (Pa) increased from 11.5 +/- 0.7, post-COI normoxia, to a peak of 22.1 +/- 2.3 during hypoxia (P less than 0.01) without a change in capillary pressure (Pc). In contrast, hypoxia changed neither Pa nor Pc in Hypox relative to an untreated normoxic control group (Normox, n = 6, P greater than 0.05). Kfs (means +/- SE in ml.min-1.Torr-1.100 g-1) for Normox (0.070 +/- 0.014), Hypox (0.082 +/- 0.024), and COI + Hypox (0.057 +/- 0.017) did not differ from one another (P greater than 0.05). Although COI markedly enhanced the pressor response to acute alveolar hypoxia, hypoxia increased neither Pc nor vascular permeability regardless of COI.     

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

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

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.     

Effect of changing vascular volume on measurement of protein reflection coefficient in ischemic lungs

In ischemic organs, the protein reflection coefficient (sigma) can be estimated by measuring blood hematocrit (Hct) and protein after increasing static vascular pressure (P(v)). Our original equation for sigma (J Appl Physiol 73: 2616-2622, 1992) assumed a constant vascular volume during convective fluid flux (). In this study, we 1) quantified the rate of vascular volume change (dV/dt) still present in ischemic single ferret lungs after 20 min of P(v) = 30 Torr and 2) developed an equation for sigma that allowed a finite dV/dt. In 25 lungs, we estimated the dV/dt after 20 min at P(v) = 30 Torr by subtracting from the rate of lung weight gain (W(L)). The relationship between (0.15 +/- 0.02 ml/min) and W(L) (0.24 +/- 0.02 g/min) was significant (R = 0.66, P < 0.001), but the slope was <1 (0.41 +/- 0.10, P < 0.05). dV/dt (0.10 +/- 0.02 ml/min) was similar in magnitude to at 20 min. The modified equation for sigma revealed that a finite dV/dt caused the original sigma measurement to underestimate true sigma. A low sigma, high, high baseline Hct, and long filtration time enhanced the error. The error was small, however, and could be minimized by adjusting experimental parameters.     

Separate effects of ischemia and reperfusion on vascular permeability in ventilated ferret lungs.

In systemic organs, ischemia-reperfusion injury is thought to occur during reperfusion, when oxygen is reintroduced to hypoxic ischemic tissue. In contrast, the ventilated lung may be more susceptible to injury during ischemia, before reperfusion, because oxygen tension will be high during ischemia and decrease with reperfusion. To evaluate this possibility, we compared the effects of hyperoxic ischemia alone and hyperoxic ischemia with normoxic reperfusion on vascular permeability in isolated ferret lungs. Permeability was estimated by measurement of filtration coefficient (Kf) and osmotic reflection coefficient for albumin (sigma alb), using methods that did not require reperfusion to make these measurements. Kf and sigma alb in control lungs (n = 5), which were ventilated with 14% O2-5% CO2 after minimal (15 +/- 1 min) ischemia, averaged 0.033 +/- 0.004 g.min-1.mmHg-1.100 g-1 and 0.69 +/- 0.07, respectively. These values did not differ from those reported in normal in vivo lungs of other species. The effects of short (54 +/- 9 min, n = 10) and long (180 min, n = 7) ischemia were evaluated in lungs ventilated with 95% O2-5% CO2. Kf and sigma alb did not change after short ischemia (Kf = 0.051 +/- 0.006 g.min-1.mmHg-1.100 g-1, sigma alb = 0.69 +/- 0.07) but increased significantly after long ischemia (Kf = 0.233 +/- 0.049 g.min-1 x mmHg-1 x 100 g-1, sigma alb = 0.36 +/- 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Phorbol myristate acetate-induced injury of isolated perfused rat lungs: neutrophil dependence

The effect of leukocyte depletion on acute lung injury produced by intravenous or intratracheal phorbol myristate acetate (PMA) administration was studied in isolated perfused rat lungs. Vascular endothelial permeability was assessed by use of the capillary filtration coefficient (Kf,c). A predicted pulmonary capillary pressure (Ppc,p) was calculated from measurements of postcapillary resistances. These parameters were measured before and 90 min after the administration of PMA, either intratracheally or intravascularly. When blood elements were present both intratracheal and intravascular PMA caused an increased Kf,c [0.27 +/- 0.02 vs. 0.99 +/- 0.22 and 0.25 +/- 0.05 vs. 0.64 +/- 0.15 (SE) ml.min-1.cmH2O-1.100 g-1, respectively; P less than 0.05] and an increased Ppc,p (8.3 +/- 0.4 vs. 74.7 +/- 18.3 and 8.7 +/- 0.8 vs. 74.2 +/- 25.1 cmH2O, respectively; P less than 0.05). Removal of circulating leukocytes abolished the increased Kf,c when PMA was given intratracheally (0.35 +/- 0.06 vs. 0.23 +/- 0.07 ml.min-1.cmH2O-1.100 g-1) or intravascularly (0.39 +/- 0.07 vs. 0.33 +/- 0.07 ml.min-1.cmH2O-1.100 g-1). In the absence of neutrophils, Ppc,p slightly increased with intratracheal PMA, from 6.9 +/- 0.5 to 10.5 +/- 1.1 cmH2O (P less than 0.05), but was unchanged at 90 min with intravascular PMA. Depletion of circulating neutrophils with an antineutrophil serum failed to block the Kf,c change with intratracheal PMA (from 0.24 +/- 0.03 to 0.42 +/- 0.09 ml.min-1.cmH2O-1.100 g-1; P less than 0.05). Ppc,p also increased from 6.9 +/- 0.6 to 19.8 +/- 6.7 cmH2O (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fast-phase transvascular fluid flux and the Fahraeus effect

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

Lung endothelial and epithelial permeability after platelet-activating factor

We investigated whether platelet-activating factor (PAF) increased epithelial or endothelial permeability in isolated-perfused rabbit lungs. PAF was either injected into the pulmonary artery or instilled into the airway of lungs perfused with Tyrode's solution containing 1% bovine serum albumin. The effect of adding neutrophils or platelets to the perfusate was also tested. Perfusion was maintained 20-40 min after adding PAF and then a fluid filtration coefficient (Kf) was determined to assess vascular permeability. At the end of each experiment, one lung was lavaged, and the lavagate protein concentration (BALP) was determined. Wet weight-to-dry weight ratios (W/D) were determined on the other lung. PAF added to the vascular space increased peak pulmonary arterial pressure (Ppa) from 13.5 +/- 3.1 (mean +/- SE) to 24.2 +/- 3.3 cmH2O (P less than 0.05). The effect was amplified by platelets [Ppa to 70.8 +/- 8.0 cmH2O (P less than 0.05)] but not by neutrophils [Ppa to 22.0 +/- 1.4 cmH2O (P less than 0.05)]. Minimal changes in Ppa were observed after instilling PAF into the airway. The Kf, W/D, and BALP of untreated lungs were not increased by injecting PAF into the vasculature or into the air space. The effect of PAF on Kf, W/D, and BALP was unaltered by adding platelets or neutrophils to the perfusate. PAF increases intravascular pressure (at a constant rate of perfusion) but does not increase epithelial or endothelial permeability in isolated-perfused rabbit lungs.     

Increased lung vascular permeability after arachidonic acid and hydrostatic challenge

Arachidonic acid (AA) metabolites are known to be potent vasoactive substances in the pulmonary circulation, whereas their influence on lung vascular permeability is still uncertain. We investigated the effect of AA bolus injection on the capillary filtration coefficient (Kf,C) of isolated rabbit lungs, recirculatingly perfused with Krebs-Henseleit albumin (1%) buffer. Kf,C was measured using repetitive sudden venous pressure elevations (7.5 Torr) and time zero extrapolation of the slope of the weight gain curve. It ranged from 1.3 to 2.4 cm3 X s-1 X Torr-1 X g-1 X 10(-4) in control lungs. Pulmonary arterial injection of AA (100 microM; in presence of 20 microM indomethacin to suppress pulmonary arterial pressure rise) during an acute hydrostatic challenge, but not at zero venous pressure, caused a greater than 10-fold increase in Kf,C. Vascular compliance was not altered. Additional experiments, performed under zero-flow conditions to avoid any ambiguity in microvascular pressure, corroborated the severalfold increase in vascular permeability, detectable within 3 min after AA application during acute hydrostatic challenge.     

Canine pulmonary filtration coefficient calculated from optical, radioisotope, and weight measurements.

Three independent methods were used to estimate filtration coefficient (Kf) in isolated dog lungs perfused with low-hematocrit (Hct) blood. Pulmonary vascular pressure was increased by 12-23 cmH2O to induce fluid filtration. Average Kf (ml.min-1 x cmH2O-1 x 100 g dry wt-1) for six lungs was 0.26 +/- 0.05 (SE) with use of equations describing conservation of optically measured protein labeled with indocyanine green. Good agreement was found when a simplified version of the multiequation theory was applied to the data (0.24 +/- 0.05). Both optical estimates were lower than those predicted by constant slope (0.55 +/- 0.07) or extrapolation (1.20 +/- 0.15) techniques, which are based on changes in total lung weight. Subsequent studies in five dog lungs investigated whether the higher Kf from weight analyses could be caused by prolonged pulmonary vascular filling. We found that 51Cr-labeled red blood cells (RBCs), monitored over the lung, continued to accumulate for 30 min after vascular pressure elevations of 9-16 cmH2O.Kf was determined by subtracting computed vascular filling from total weight change (0.28 +/- 0.06) and by perfusate Hct changes determined from radiolabeled RBCs (0.23 +/- 0.04). These values were similar to those obtained from analysis of optical data with the complete model (0.30 +/- 0.06), the simplified version (0.26 +/- 0.05), and from optically determined perfusate Hct (0.16 +/- 0.03). However, constant slope (0.47 +/- 0.04) and extrapolation (0.57 +/- 0.07) computations of Kf were higher than estimates from the other methods. Our studies indicate that prolonged blood volume changes may accompany vascular pressure elevations and produce overestimates of Kf with standard weight measurement techniques. However, Kf computed from optical measurements is independent of pulmonary blood volume changes.     

Estimation of the pulmonary microvascular reflection coefficient to protein in dogs

We used a new technique to estimate the pulmonary microvascular membrane reflection coefficient to plasma protein (sigma d) in anesthetized dogs. In five animals we continuously weighed the lower left lung lobe and used a left atrial balloon to increase the pulmonary microvascular pressure (Pc). We determined the relationship between the rate of edema formation (S) and Pc and estimated the fluid filtration coefficient (Kf) as delta S/delta Pc. From the S vs. Pc relationship and Kf, we estimated the Pc at which S/Kf = 10 mmHg for each dog. This pressure (P10) was 38.0 +/- 5.8 (SD) mmHg, and the plasma protein osmotic pressure (pi c) was 14.9 +/- 3.7 mmHg. In five additional dogs in which we decreased pi c to 2.9 +/- 1.7 mmHg, P10 = 27.2 +/- 2.6 mmHg. The P10 vs. pi c regression line fit to the data from all 10 dogs was P10 = 0.92 pi c +/- 24.4 mmHg (r = 0.88). We estimated sigma d from the slope of the regression line as sigma d = square root of delta P10/delta pi c. With this technique, we estimated that, with 95% probability, sigma d lies between 0.72 and unity. This is higher than most previous sigma d estimates.     

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

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

Simultaneous measurement of fluid and protein permeability in isolated rabbit lungs during edema.

Fluid conductance and protein permeability have been studied in isolated perfused lung models of pulmonary edema. However, previous studies have not investigated changes of both fluid conductance and protein permeability in the same isolated lung preparation after injury. Arachidonic acid (AA) metabolites are involved in the inflammatory processes that lead to the development of pulmonary edema. The hemodynamic effects of AA have been well established; however, controversy exists concerning the ability of AA to alter the permeability of the pulmonary microvasculature to fluid and protein. The purpose of this study was to simultaneously determine whether transvascular fluid conductance and protein permeability are increased in isolated perfused rabbit lungs with pulmonary edema induced by AA. Indomethacin (80 microM) was added to the perfusate to inhibit the hemodynamic effects of AA and produce a pressure-independent model of pulmonary edema. Fluid conductance was assessed by determination of the capillary filtration coefficient (Kf), and protein permeability was evaluated by measurement of 125I-albumin clearance. The injection of AA (3 mg/200 ml of perfusate) into the pulmonary arterial catheter resulted in an increase in lung weight over the remaining 30-min experimental period. Kf (microliter.s-1 x cmH2O-1 x g dry lung-1) was increased (P < 0.05) in AA-treated lungs at 10 and 30 min post-AA injection when compared with control lungs and baseline values (determined 10 min before AA injection). Albumin clearance was also greater (P < 0.05) in lungs that received AA. 125I-albumin clearance was measured at different rates of fluid flux produced by elevation of venous pressure.(ABSTRACT TRUNCATED AT 250 WORDS)