Noninvasive measures of radiolabeled dextran transport in in situ rabbit lung.

UNLABELLED: Dextrans are nontoxic and can be obtained in a wide variety of molecular weights. The purpose of this study was to label 6-kDa and 40-kDa dextrans with gamma- (99mTc) and positron- (18F) emitting radioisotopes and monitor their transport across the pulmonary microvascular barrier. METHODS: External scan measurements for radiolabeled uncharged dextrans, albumin and red blood cells were obtained in eight blood-perfused in situ rabbit lung preparations. After 3 hr of external scanning, the lungs were removed for postmortem and extravascular distribution volume calculations. Extravascular distribution volumes were obtained in six additional rabbits following 4 hr of dextran perfusion to compare the effect of time. The normalized slope index (NSI), a measure of transvascular transport rate, was calculated for each diffusible tracer. RESULTS: The mean NSI for albumin (0.001676 +/- 0.000537 min-1) was significantly lower than NSI for the 40-kDa dextran (0.002303 +/- 0.0005426 min-1) as well as the 6-kDa dextran (0.004312 +/- 0.001134 min-1). The difference between the 6-kDa and the 40-kDa dextrans was also significant. After 4 hr of equilibration, distribution volumes were not significantly different than those obtained at 3 hr. CONCLUSION: Dextrans can be radiolabeled with gamma and positron emitters and small dextrans traverse the lung microvascular barrier more rapidly than albumin. Our results suggest that the use of small dextrans rather than albumin can reduce scan times in clinical applications and minimize motion artifact associated with the noninvasive gamma detection method.

Comparison of the pulmonary dysfunction caused by cardiogenic and noncardiogenic pulmonary edema.

We designed a series of experiments to compare the pulmonary dysfunction observed in models of cardiogenic and noncardiogenic pulmonary edema in chronically instrumented awake sheep. Cardiogenic pulmonary edema was induced by inflating the balloon of a Foley catheter surgically positioned in the mitral valve orifice causing increased left atrial pressure (increases PLA). Noncardiogenic pulmonary edema was induced by intravenous infusion of Perilla ketone (PK). Calculated microvascular pressure remained constant during PK infusion but increased from 9.4 +/- 0.7 to 42.8 +/- 2.4 cm H2O during increases PLA. Comparable increases in lung lymph flow (QL) were observed in the two protocols (five to seven times baseline). Pulmonary edema as quantified by chest radiograph scores increased from 0 (normal) to 2.9 +/- 0.5 and 3.4 +/- 0.1 in the PK and increases PLA groups, respectively. Room air alveolar to arterial oxygen pressure difference (P[A-a]O2) increased from 24 +/- 3 to 46 +/- 7 mm Hg in the PK group and from 23 +/- 4 to 56 +/- 6 mm Hg in the increases PLA group. Dynamic compliance of the lungs (Cdyn) expressed as the percentage of the baseline value decreased to 53 +/- 7 and 50 +/- 7% in the PK and increases PLA groups, respectively. Resistance to airflow across the lungs (RL) increased from 2.5 +/- 0.6 to 3.3 +/- 0.8 cm H2O.L-1.sec-1 in the PK group and from 1.4 +/- 0.3 to 4.2 +/- 1.1 in the increases PLA group. Significant correlations were observed between changes in the severity of pulmonary edema observed on chest radiographs, Cdyn, delta P(A-a)O2, and QL in both the increases PLA groups. We conclude that similar degrees of pulmonary edema, regardless of the mechanism, are associated with similar changes in QL, Cdyn, and delta P(A-a)O2. Hydrostatic pulmonary edema appeared to cause greater changes in RL than that resulting from increased microvascular permeability.

Modeling flux of free and protein-bound radioisotopes into the pulmonary interstitium.

Several groups of investigators are using external detection of radiolabeled protein to study the flux of protein from plasma into the pulmonary interstitium. A basic assumption for these studies has been that the unbound (free) tracer concentration is small and insignificant. The purpose of this study is to evaluate how free tracer influences the determination of normalized slope index. A five-compartment model for the lung was used with transport equations for both unbound and bound nuclide flux. Parameters of the unbound and bound transport equations were varied to evaluate the sensitivity of normalized slope index to each parameter. The model was also compared with published protein flux data to investigate the validity of the transport model. Application of the model to external scan data provides a sensitive method for evaluating the flux of bound and unbound tracers into the pulmonary interstitium. We conclude that because the distribution volume for unbound tracer is large with respect to protein distribution volume, even a small amount of unbound tracer (2-5%) can create large errors in the determination of normalized slope index.

Effects of air embolism on sheep lung fluid volumes.

Changes in lung fluid volumes and hyaluronan clearance were measured in six awake sheep during increased microvascular permeability induced by pulmonary air embolism (AE). After a 1- to 2-h baseline, filtered room air was infused through a proximal port of a Swan-Ganz catheter for 2 h at a rate sufficient to double pulmonary vascular resistance. The air infusion was discontinued, and the sheep were monitored for an additional 2 h (recovery). Lung lymph flow and protein flux increased during air infusion and continued to increase during recovery. During AE, lymph-to-plasma ratio for albumin decreased while lymph-to-plasma ratio for large protein remained the same. This would suggest that both microvascular pressure and microvascular permeability increase during AE. Protein clearance increased similarly for all protein sizes during AE and recovery. After 2 h of recovery, interstitial and extravascular volumes were elevated with no change in cellular volume. The volume of the interstitium available to albumin was more than twice control. The fraction of the interstitium that excludes albumin was calculated to be 0.32 +/- 0.04, with a 51% reduction in absolute excluded volume 2 h after AE. Clearance of hyaluronan by the lymphatics (normalized to baseline) increased 6- to 10-fold during and after AE. It was estimated that < 2% of the total hyaluronan in the lung would be cleared in 24 h under baseline conditions. This amount increased to approximately 11% under AE conditions and approximately 15% under recovery conditions. Changes in lung fluid volumes and protein clearance indicate increased microvascular permeability 2 h after AE.(ABSTRACT TRUNCATED AT 250 WORDS)

Fluid balance in sheep lungs before and after extracorporeal perfusion.

Lung fluid balance was studied in sheep under the following conditions: 1) unanesthetized, standing in a metabolic cage; 2) anesthetized, in a supine position; 3) 1 h after extracorporeal perfusion; and 4) either 4-6 h after extracorporeal perfusion (i.e., control experiments) or 1.5 h after left atrial pressure was increased by 15 cmH2O. Lung lymph flow rate (QL), plasma and lymph concentrations for nine protein fractions, urea permeability-surface area product (PS), urea effective diffusivity (D1/2S), and extravascular lung water (VE) were measured under each condition. Bloodless wet and dry lung weights were measured at the end of each experiment. QL increased and lymph-to-plasma concentration ratio for total proteins (L/P) decreased after the sheep were anesthetized and placed in a supine position. This possibly resulted from an increase in microvascular pressure induced by anesthesia and/or reorientation of the lungs. PS, D1/2S, and VE decreased, indicating a decrease in perfused surface area associated with a decreased cardiac output or alteration in lung orientation. After 90 min of extracorporeal perfusion, no significant differences were found in QL, PS, and D1/2S compared with those measured during the anesthetized period. No changes in PS or D1/2S could be detected after an average of 4.2 h of extracorporeal perfusion. The average bloodless wet-to-dry lung weight ratio [(W-D)/D] was 3.77 +/- 0.12, well within the range for normal sheep lungs. An increase in venous pressure of 15 cmH2O produced a response similar to that observed in the unanesthetized sheep lung lymph preparation: QL increased, L/P decreased, PS and D1/2S did not increase, and VE and (W-D)/D increased slightly.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary vascular resistance distribution and recruitment of microvascular surface area.

To test the hypothesis that the distribution of hemodynamic resistance is involved in the control of pulmonary capillary surface area, we measured permeability-surface area product (PS) and longitudinal resistance distribution (LRD) as functions of perfusion rate in isolated rabbit lungs under zone II conditions (n = 10) and through the zone II-III transition (n = 4). PS, considered to be indicative of functioning capillary surface area, was measured with the aid of the diffusion-limited tracer [14C]propanediol, whereas LRD was determined using a viscous bolus technique. LRD was seen to change character with increasing flow and increasing PS/surface area, becoming bimodal with low central resistance as full capillary recruitment was approached in zone III. Effects of hypoxic ventilation were studied in zone II in five lungs; it was found that hypoxia altered the LRD and eradicated the normoxic dependence of PS/surface area on perfusion rate. It was concluded that LRD is involved in the determination of functioning capillary surface area.

Evaluation of perilla ketone-induced unilateral lung injury using external gamma scanning.

We used a modified external gamma scanning technique to quantitate right and left lung permeability changes to iodinated sheep albumin before and after perilla ketone (PK)-mediated unilateral lung injury in seven anesthetized sheep. Three portable gamma scintillation probes containing 2-in. NaI crystals detected radioactivities of 51Cr-labeled red blood cells and 125I-labeled albumin over the right and left lungs and blood, respectively. Radioactivities were monitored for 1 h before and 3 h after infusion of 25 mg/kg PK into a single lung. Calculation of normalized slope index (NSI) (Roselli and Riddle, J. Appl. Physiol. 67: 2343-2350, 1989) over the 30-min interval before PK and over the 60- to 90-min interval after PK for each lung revealed a four- to five-fold NSI increase in lungs receiving PK (0.00237 +/- 0.00065 to 0.0109 +/- 0.0016 min-1) and no increase in contralateral control lungs (0.00214 +/- 0.00065 to 0.00201 +/- 0.00032 min-1). Observed changes in NSI were consistent with postmortem evaluations of each lung. Lungs receiving PK had significantly higher wet-to-dry lung weight ratios and extravascular lung water volumes than contralateral control lungs. Measured bloodless wet-to-dry lung weight ratios were 5.68 +/- 0.39 and 3.27 +/- 0.27 (P < 0.05) for PK and control lungs, respectively.

Comparison of labeled propanediol and urea as markers of lung vascular injury.

The purpose of these studies was a comparison of [14C]urea (U) and 1,3-[14C]propanediol (Pr) as measures of lung vascular permeability-surface area (PS) under base-line conditions and after lung injury caused by alloxan infusion in isolated perfused dog lungs. Indicator mixtures of 125I-albumin, 51Cr-red blood cells, 3HOH, and U or Pr were injected under base-line conditions, after 1.2 g of alloxan, and after an additional 0.8 g of alloxan. Indicator-dilution curves were analyzed from sampled outflow blood to provide PS, the square root of effective extravascular diffusivity multiplied by exchange surface area (D1/2S), and extravascular lung water (EVLW) from the tracer mean transit times (VW). Results show that alloxan increases PS and D1/2S for U, D1/2S for Pr, and VW and EVLW by desiccation. All indicator-dilution parameters correlate significantly with alloxan dose. Interpretation of Pr transport suggests that materials with lipid and hydrophilic pathways might be used in conjunction with U to minimize the effects of surface area changes and increase the sensitivity of these tracers to permeability alteration. In addition Pr may be a useful alternative to U as a marker of vascular damage.

Evaluating flux of labeled albumin into the pulmonary interstitium of sheep lungs.

A noninvasive method was used to measure the movement of 131I-labeled albumin across the pulmonary microvascular barrier of a blood-perfused in situ sheep lung lymph preparation. After injection of labeled albumin into the blood, external measurements of gamma activity were taken for 2 h. The interstitial concentrations were calculated by applying the external activities and sampled lung lymph concentrations to a mass transport model. For the external activities and lymph activities to yield the same quantitative results, two modifications were necessary. First, lymph concentrations were corrected for transport delay from the lymphatic system. Second, externally detected radioactivity had to be corrected for the contribution of unbound nuclide. Application of a mathematical model to the data indicated the extravascular distribution volume for albumin was 79% of the pulmonary blood volume, and the extravascular distribution volume for radiolabeled iodide was 4.42 times greater than the pulmonary blood volume. The permeability-surface area product for iodide in the lung was estimated to be 0.274 ml.min-1.g blood-free dry lung wt-1. The transport delay in the lymphatic system was approximately 30-45 min and represented a volume of 1.44-2.80 ml.

Effects of Perilla ketone on the in situ sheep lung.

We studied the effects of three different doses (15, 20, and 25 mg/kg) of Perilla ketone (PK) on the blood-perfused in situ sheep lung while obtaining external measurements of lung transvascular protein flux. Lymph flow and lymphatic protein clearance increased significantly after all doses of PK. Severe pulmonary edema was confirmed by high postmortem wet-to-dry lung weight ratios and increased extravascular lung water from multiple indicator-dilution studies. Urea permeability-surface area product and effective diffusivity from multiple indicator-dilution studies also increased after PK infusion. Because we observed no evidence of increased capillary pressure or increased microvascular surface area after PK, we conclude that PK significantly increased pulmonary microvascular permeability. Certain aspects of the in situ PK response appeared to be dose dependent. The lungs responded rather quickly to high doses of PK, but an apparent latency period was noted with low doses of PK. Postmortem wet-to-dry lung weight ratios were always high but did not suggest dose dependence. However, times of postmortem measurements were not the same for all doses of PK. The external scan technique appeared to be sensitive to changes that occurred in the lung after PK. Externally detected albumin interstitial-to-plasma mass (mass I/P) ratios were substantially higher after PK than during control in situ studies. In some experiments, final mass I/P ratios increased above 4 approximately 2.0 h after PK compared with control values of 0.2 and 0.4. A delay time between injection and change in mass I/P slope was also observed, which decreased with increasing dose of PK. PK causes a permeability injury in the in situ sheep lung and provides a useful model for studying the sensitivity of permeability measurement techniques such as the external gamma-ray detection method.

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.

Measurement of lung fluid volumes and albumin exclusion in sheep.

A radioactive tracer technique was used to determine interstitial diethylenetriaminepentaacetic acid (DTPA) and albumin distribution volume in sheep lungs. 125I- and/or 131I-labeled albumin were injected intravenously and allowed to equilibrate for 24 h. 99mTc-labeled DTPA and 51Cr-labeled erythrocytes were injected and allowed to equilibrate (2 h and 15 min, respectively) before a lethal dose of thiamylal sodium. Two biopsies (1-3 g) were taken from each lung and the remaining tissue was homogenized for wet-to-dry lung weight and volume calculations. Estimates of distribution volumes from whole lung homogenized samples were statistically smaller than biopsy samples for extravascular water, interstitial 99mTc-DTPA, and interstitial albumin. The mean fraction of the interstitium (Fe), which excludes albumin, was 0.68 +/- 0.04 for whole lung samples compared with 0.62 +/- 0.03 for biopsy samples. Hematocrit may explain the consistent difference. To make the Fe for biopsy samples match that for homogenized samples, a mean hematocrit, which was 82% of large vessel hematocrit, was required. Excluded volume fraction for exogenous sheep albumin was compared with that of exogenous human albumin in two sheep, and no difference was found at 24 h.

Optical measurement of isolated canine lung filtration coefficients after alloxan infusion.

In this study, lung filtration coefficient (Kfc) was measured in eight isolated canine lung preparations by using three methods: standard gravimetric (Std), blood-corrected gravimetric (BC), and optical. The lungs were held in zone III conditions and were subjected to an average venous pressure increase of 8.79 +/- 0.93 (mean +/- SD) cmH2O. The permeability of the lungs was increased with an infusion of alloxan (75 mg/kg). The resulting Kfc values (in milliliters . min-1 . cmH2O-1 . 100 g dry lung weight-1) measured by using Std and BC gravimetric techniques before vs. after alloxan infusion were statistically different: Std, 0.527 +/- 0.290 vs. 1. 966 +/- 0.283; BC, 0.313 +/- 0.290 vs. 1.384 +/- 0.290. However, the optical technique did not show any statistical difference between pre- and postinjury with alloxan, 0.280 +/- 0.305 vs. 0.483 +/- 0. 297, respectively. The alloxan injury, quantified by using multiple-indicator techniques, showed an increase in permeability and a corresponding decrease in reflection coefficient for albumin (sigmaf). Because the optical method measures the product of Kfc and sigmaf, this study shows that albumin should not be used as an intravascular optical filtration marker when permeability is elevated. However, the optical technique, along with another means of measuring Kfc (such as BC), can be used to calculate the sigmaf of a tracer (in this study, sigmaf of 0.894 at baseline and 0.348 after injury). Another important finding of this study was that the ratio of baseline-to-injury Kfc values was not statistically different for Std and BC techniques, indicating that the percent contribution of slow blood-volume increases does not change because of injury.

Effects of flow heterogeneity on the measurement of capillary exchange in the lung.

The effects of flow heterogeneity on the measurement of transcapillary escape of small molecules for perfused in situ sheep lungs were evaluated. Lungs were studied at five flows (1.5-5.0 l/min) ranging from zone 1 to zone 3 conditions. At each flow, multiple indicator-dilution curves were collected using 14C-labeled urea (U) or butanediol (B) as the diffusing tracer, and radiolabeled 15-microns microspheres were injected. The lungs were removed, dried, sectioned, weighed, and counted for microsphere radioactivity. Flow heterogeneity expressed as relative dispersion, decreased with increasing flow, from 0.838 +/- 0.179 (mean +/- SD, n = 8) to 0.447 +/- 0.119 (n = 6). We applied homogeneous flow models of capillary exchange to compute permeability-surface area product (PS) and a related parameter, D1/2S, for diffusing tracers. (D is effective diffusivity of capillary exchange.) PS and D1/2S increased to a maximum with increasing flow, but the ratio of D1/2SU to D1/2SB remained constant. A new model incorporating flow heterogeneity and recruitment (the variable recruitment model) was used. The variable recruitment model described the effects of flow on capillary recruitment, but incorporating heterogeneity into the computation did not alter D1/2S values from those computed assuming homogeneous flow.

Optical measurement of isolated canine lung filtration coefficients at normal hematocrits.

In this study, lung filtration coefficient (Kfc) values were measured in eight isolated canine lung preparations at normal hematocrit values using three methods: gravimetric, blood-corrected gravimetric, and optical. The lungs were kept in zone 3 conditions and subjected to an average venous pressure increase of 10.24 +/- 0.27 (SE) cmH2O. The resulting Kfc (ml . min-1 . cmH2O-1 . 100 g dry lung wt-1) measured with the gravimetric technique was 0.420 +/- 0.017, which was statistically different from the Kfc measured by the blood-corrected gravimetric method (0.273 +/- 0.018) or the product of the reflection coefficient (sigmaf) and Kfc measured optically (0. 272 +/- 0.018). The optical method involved the use of a Cellco filter cartridge to separate red blood cells from plasma, which allowed measurement of the concentration of the tracer in plasma at normal hematocrits (34 +/- 1.5). The permeability-surface area product was measured using radioactive multiple indicator-dilution methods before, during, and after venous pressure elevations. Results showed that the surface area of the lung did not change significantly during the measurement of Kfc. These studies suggest that sigmafKfc can be measured optically at normal hematocrits, that this measurement is not influenced by blood volume changes that occur during the measurement, and that the optical sigmafKfc agrees with the Kfc obtained via the blood-corrected gravimetric method.

Regional measurements of pulmonary edema by using magnetic resonance imaging.

A three-dimensional magnetic resonance imaging (MRI) method to measure pulmonary edema and lung microvascular barrier permeability was developed and compared with conventional methods in nine mongrel dogs. MRIs were obtained covering the entire lungs. Injury was induced by injection of oleic acid (0.021-0.048 ml/kg) into a jugular catheter. Imaging followed for 0.75-2 h. Extravascular lung water and permeability-related parameters were measured from multiple-indicator dilution curves. Edema was measured as magnetic resonance signal-to-noise ratio (SNR). Postinjury wet-to-dry lung weight ratio was 5.30 +/- 0.38 (n = 9). Extravascular lung water increased from 2.03 +/- 1.11 to 3.00 +/- 1.45 ml/g (n = 9, P < 0.01). Indicator dilution studies yielded parameters characterizing capillary exchange of urea and butanediol: the product of the square root of equivalent diffusivity of escape from the capillary and capillary surface area (D1/2S) and the capillary permeability-surface area product (PS). The ratio of D1/2S for urea to D1/2S for butanediol increased from 0.583 +/- 0.027 to 0.852 +/- 0.154 (n = 9, P < 0.05). Whole lung SNR at baseline, before injury, correlated with D1/2S and PS ratios (both P < 0.02). By using rate of SNR change, the mismatch of transcapillary filtration flow and lymph clearance was estimated to be 0.2-1.8 ml/min. The filtration coefficient was estimated from these values. Results indicate that pulmonary edema formation during oleic acid injury can be imaged regionally and quantified globally, and the results suggest possible regional quantification by using three-dimensional MRI.

Laser system for measuring small changes in plasma tracer concentrations.

The authors developed a laser-diode system that can be used for on-line optical concentration measurements in physiologic systems. Previous optical systems applied to whole blood have been hampered by artifacts introduced by red blood cells (RBCs). The system introduced here uses a commercially available filter cartridge to separate RBCs from plasma before plasma concentration measurements are made at a single wavelength. The filtering characteristics of the Cellco filter cartridge (#4007-10, German-town, MD) were adequate for use in the on-line measurement system. The response time of the filter cartridge was less than 40 seconds, and the sieving characteristics of the filter for macromolecules were excellent, with filtrate-to-plasma albumin ratios of 0.98 +/- 0.11 for studies in sheep and 0.94 +/- 0.15 for studies in dogs. The 635-nm laser diode system developed was shown to be more sensitive than the spectrophotometer used in previous studies (Klaesner et al., Annals of Biomedical Engineering, 1994; 22, 660-73). The new system was used to measure the product of filtration coefficient (Kfc) and reflection coefficient for albumin (delta f) in an isolated canine lung preparation. The delta fKfc values [mL/(cmH2O.min.100 g dry lung weight)] measured with the laser diode system (0.33 +/- 0.22) compared favorably with the delta fKfc obtained using a spectrophotometer (0.27 +/- 0.20) and with the Kfc obtained using the blood-corrected gravimetric method (0.32 +/- 0.23). Thus, this new optical system was shown to accurately measure plasma concentration changes in whole blood for physiologic levels of Kfc. The same system can be used with different optical tracers and different source wavelengths to make optical plasma concentration measurements for other physiologic applications.

Quantification of lung microvascular injury with ultrasound.

Quantification of water and solute exchange rates across the lung microvascular barrier (LMB) may be an important early-warning indicator of pulmonary microvascular diseases such as acute respiratory distress syndrome. Our objective was to determine the degree to which osmotic water movement across the LMB induced by injection of hypertonic solutions of NaCl and glucose could be detected downstream from the lung with a specialized ultrasonic velocity (USV) transducer manufactured by Transonic Systems. We hypothesized that mathematical modeling of the osmotic transients (OT) would yield estimates of osmotic exchange parameters that were sensitive to microvascular injury. Two groups of six dogs were studied under baseline conditions and after injury with high dose (HD) or low dose (LD) oleic acid. Osmotic conductances (sigmaK(1), sigmaK(2)), and volumes (V(1), V(2)) of two extravascular spaces were estimated by fitting the mathematical model to the OT data. HD results (mean +/- standard error) indicated a significant decrease (by paired t test) in sigmaK(1) from 1.59 +/- 0.09 to 1.04 +/- 0.015 [ml h(-1) (mosm/l)(-1) g(-1) WLW)], an increase in sigmaK(2) from 0.20 +/- 0.08 to 0.32 +/- 0.12 [ml h(-1) (mosm/l)(-1) g(-1)], and a significant increase in V2 from 23.26 +/- 2.51 to 78.0 +/- 15.23 (ml) for NaCl injections. LD V2 estimated from NaCl increased significantly from 21.57 +/- 2.15 to 37.59 +/- 2.36 (ml), sigmaK2 increased from 0.09 +/- 0.03 to 0.17 +/- 0.04 and no significant change in sigmaK(1) was found. Baseline glucose sigmaK(1), sigmaK(2), and V1 in the LD series were 2.08 +/- 0.18, 0.64 +/- 0.19 [ml h(-1) (mosm/l)(-1) g(-1)] and 13.08 +/- 1.89 (ml), respectively, and did not change significantly with injury. We conclude that OT data measured by USV is a sensitive and informative indicator of LMB osmotic properties, and may be useful for quantification of LMB permeability changes due to acute injury. We further conclude that V(1) represents microvascular endothelial volume and V(2) is an estimate of interstitial volume.

Relative quantification of pulmonary edema with noncontrast-enhanced MRI.

Pulmonary edema is a debilitating effect of acute respiratory distress syndrome. The ability to measure it noninvasively with high sensitivity and in three dimensions could be useful in not only detection but also in assessment and guidance of treatment. To this end, a three-dimensional MRI pulse sequence to measure the formation of edema was developed and tested. Another sequence was tested to measure blood flow in distal pulmonary arteries. Pulmonary edema was induced in nine dogs via venous injections of oleic acid. Edema was verified by wet-to-dry weight ratio (5.30 +/- .38) and extra-vascular lung water at baseline (2.03 +/- 1.12 ml/g dry lung weight) versus postinjury (3.00 +/- 1.45 ml/g) (P < .005). The signal-to-noise ratio within the lungs increased from 5.47 +/- 1.00 at baseline to 7.51 +/- 1.96 (P < .005), and the time course of edema formation was resolved. Results from MR phase-contrast blood flow measurements were variable. The authors conclude that the three-dimensional scan provides a sensitive relative quantification of pulmonary edema formation without the use of contrast agents or ionizing radiation.

Noninvasive measurements of albumin flux into lung interstitium with increased microvascular pressure.

The purpose of this study was to determine the effect of increasing left atrial pressure on noninvasive measurements of radiolabeled albumin normalized slope index (NSI). Using portable gamma scintillation detectors, we monitored radioactivities of 131I-labeled albumin and 51Cr-labeled red blood cells in the blood and over the lung of six anesthetized sheep before and 2 h after a 9- to 14-Torr increase in left atrial pressure. Measurements of NSI for 131I-albumin decreased > 50% after a step increase in left atrial pressure. We interpreted the data using a model that has been used to successfully describe unsteady-state lymph flow and protein concentrations after vascular pressure increases in sheep. Model predictions strongly suggest that the reduction in NSI is due to rapid fluid and solute removal from the interstitium via the lymphatics. The theoretical model was able to predict external scan data and lung lymph protein concentrations only when a change in lymphatic conductance (LI) or initial lymphatic pressure (P0) was imposed at the time of increased pressure. On average, model-predicted increases in LI were sevenfold, whereas predicted decreases in P0 were four- to fivefold. Imposed changes in LI and P0 opposed increases in interstitial fluid volume after increased pressure. This was consistent with normal-to-low postmortem measurements of bloodless wet-to-dry lung weight ratios. In summary, these results indicate that changes in the rate of fluid removal from the interstitium can significantly alter NSI, and in this case, NSI does not reflect pulmonary microvascular permeability. In sheep, increases in the lymphatics' ability to remove interstitial fluid may occur with relatively small increases in microvascular pressure.