Effect of lung inflation on regional lung expansion in supine and prone rabbits

At functional residual capacity, lung expansion is more uniform in the prone position than in the supine position. We examined the effect of positive airway pressure (Paw) on this position-dependent difference in lung expansion. In supine and prone rabbits postmortem, we measured alveolar size through dependent and nondependent pleural windows via videomicroscopy at Paw of 0 (functional residual capacity), 7, and 15 cmH2O. After the chest was opened, alveolar size was measured in the isolated lung at several transpulmonary pressures (Ptp) on lung deflation. Alveolar mean linear intercept (Lm) was measured from the video images taken in situ. This was compared with those measured in the isolated lung to determine Ptp in situ. In the supine position, the vertical Ptp gradient increased from 0.52 cmH2O/cm at 0 cmH2O Paw to 0.90 cmH2O/cm at 15 cmH2O Paw, while the vertical gradient in Lm decreased from 2.17 to 0.80 microns/cm. In the prone position, the vertical Ptp gradient increased from 0.06 cmH2O/cm at 0 cmH2O Paw to 0.35 cmH2O/cm at 15 cmH2O Paw, but there was no change in the vertical Lm gradient. In anesthetized paralyzed rabbits in supine and prone positions, we measured pleural liquid pressure directly at 0, 7, and 15 cmH2O Paw with dependent and nondependent rib capsules. Vertical Ptp gradients measured with rib capsules were similar to those estimated from the alveolar size measurements. Lung inflation during mechanical ventilation may reduce the vertical nonuniformities in lung expansion observed in the supine position, thereby improving gas exchange and the distribution of ventilation.     

Effect of regional lung inflation on ventilation heterogeneity at different length scales during mechanical ventilation of normal sheep lungs

Heterogeneous, small-airway diameters and alveolar derecruitment in poorly aerated regions of normal lungs could produce ventilation heterogeneity at those anatomic levels. We modeled the washout kinetics of (13)NN with positron emission tomography to examine how specific ventilation (sV) heterogeneity at different length scales is influenced by lung aeration. Three groups of anesthetized, supine sheep were studied: high tidal volume (Vt; 18.4 ± 4.2 ml/kg) and zero end-expiratory pressure (ZEEP) (n = 6); low Vt (9.2 ± 1.0 ml/kg) and ZEEP (n = 6); and low Vt (8.2 ± 0.2 ml/kg) and positive end-expiratory pressure (PEEP; 19 ± 1 cmH(2)O) (n = 4). We quantified fractional gas content with transmission scans, and sV with emission scans of infused (13)NN-saline. Voxel (13)NN-washout curves were fit with one- or two-compartment models to estimate sV. Total heterogeneity, measured as SD[log(10)(sV)], was divided into length-scale ranges by measuring changes in variance of log(10)(sV), resulting from progressive filtering of sV images. High-Vt ZEEP showed higher sV heterogeneity at <12- (P < 0.01), 12- to 36- (P < 0.01), and 36- to 60-mm (P < 0.05) length scales compared with low-Vt PEEP, with low-Vt ZEEP in between. Increased heterogeneity was associated with the emergence of low sV units in poorly aerated regions, with a high correlation (r = 0.95, P < 0.001) between total heterogeneity and the fraction of lung with slow washout. Regional mean fractional gas content was inversely correlated with regional sV heterogeneity at <12- (r = -0.67), 12- to 36- (r = -0.74), and >36-mm (r = -0.72) length scales (P < 0.001). We conclude that sV heterogeneity at length scales <60 mm increases in poorly aerated regions of mechanically ventilated normal lungs, likely due to heterogeneous small-airway narrowing and alveolar derecruitment. PEEP reduces sV heterogeneity by maintaining lung expansion and airway patency at those small length scales.     

Tracer kinetic model of regional pulmonary function using positron emission tomography.

To determine the spatial distributions of pulmonary perfusion, shunt, and ventilation, we developed a compartmental model of regional (13)N-labeled molecular nitrogen ((13)NN) kinetics measured from positron emission tomography (PET) images. The model features a compartment for right heart and pulmonary vasculature and two compartments for each region of interest: 1) aerated alveolar units and 2) alveolar units with no gas content (shunting). The model was tested on PET data from normal animals (dogs and sheep) and from animals with experimentally injured lungs simulating acute respiratory distress syndrome. The analysis yielded estimates of regional perfusion, shunt fraction, and specific ventilation with excellent goodness-of-fit to the data (R(2) > 0.99). Model parameters were estimated to within 10% accuracy in the presence of exaggerated levels of experimental noise by using a Monte Carlo sensitivity analysis. Main advantages of the present model are that 1) it separates intraregional blood flow to aerated alveolar units from that shunting across nonaerated units and 2) it accounts and corrects for intraregional tracer removal by shunting blood when estimating ventilation from subsequent washout of tracer. The model was thus found to provide estimates of regional parameters of pulmonary function in sizes of lung regions that could potentially approach the intrinsic resolution for PET images of (13)NN in lung (approximately 7.0 mm for a multiring PET camera).     

Distribution of pulmonary ventilation using Xe-enhanced computed tomography in prone and supine dogs.

Xe-enhanced computed tomography (CT; Xe-CT) is a method for the noninvasive measurement of regional pulmonary ventilation in intact subjects, determined from the washin and washout rates of the radiodense, nonradioactive gas Xe, as measured in serial CT scans. We used the Xe-CT ventilation method, along with other quantitative CT measurements, to investigate the distribution of regional lung ventilation and air content in healthy, anesthetized, mechanically ventilated dogs in the prone and supine postures. Vertical gradients in regional ventilation and air content were measured in five mongrel dogs in both prone and supine postures at four axial lung locations. In the supine position, ventilation increased with dependent location, with a mean slope of 7.3%/cm lung height, whereas no ventilation gradients were found at any location in the prone position. These results agree quantitatively with other published studies. In addition, six different animals were studied (3 supine, 3 prone) to examine the longitudinal distribution of ventilation and air content. The prone lungs were more uniformly inflated compared with the supine, which were less well expanded at the base than apex. Ventilation index, a measure of regional ventilation relative to whole lung ventilation, increased steeply from apex to base in the supine animals, whereas it was again more uniform in the prone condition. We conclude that the Xe-CT method provides a reasonable, quantitative measurement of regional ventilation and promises to be a valuable tool for the noninvasive determination of regional lung function.     

Obesity alters regional ventilation in lateral decubitus position

Alterations of regional ventilation were determined as a function of body position in five morbidly obese subjects using 81mKr to assess ventilation (V) and 127Xe at equilibrium to determine lung volume (V). With subjects in seated and supine positions, the left lung contributed an average of 43% of the total V/V. When the apical-basal gradient within each lung was examined in subjects in the seated position, V/V was greatest in the dependent (basal) regions in half of the subjects, whereas the others showed greater V/V near the upper lung regions. All obese subjects preferentially ventilated the nondependent lung in both the left and right lateral decubitus positions. In a control group of three nonobese subjects, V/V was found to be equally distributed between left and right lungs in both the seated and supine positions. In contrast with the results in the obese group, V/V was slightly greater in the dependent lung in both lateral decubitus positions. Although the combination of 127Xe images and He-dilution measurement of functional residual capacity in the lateral decubitus positions indicated a reduction in the volume of the dependent lung of the obese when compared with values in the seated position, other factors affecting the mechanical function of either the diaphragm or the intercostal muscles could also have produced these positional alterations of ventilation.     

Quantification of regional V/Q ratios in humans by use of PET. II. Procedure and normal values

Regional measurements of tissue isotope concentration, made using positron emission tomography (PET), allow tracer models to be used in a quantitative manner to provide topographic distributions of many structural and functional parameters, each derived for the same well-defined lung element. In this paper we describe a technique to measure regional ventilation-perfusion ratios (V/Q), in absolute units, by use of PET and the continuous intravenous infusion of an inert gas isotope, 13N, and report on measurements made in 12 normal subjects (4 smokers). Data were obtained from a single lung section (slice thickness, 1.7 cm full width at half-maximum response to a line source) at the level of the right ventricle in the supine posture during quiet breathing. For the 12 subjects, volume-weighted mean values of V/Q, averaged over individual right and left lung fields, ranged from 0.50 to 1.29. Analysis of these means showed no difference between lungs: right, 0.80 +/- 0.23 SD; left, 0.76 +/- 0.20 SD. Topographically, a systematic fall of V/Q in the ventrodorsal direction was observed in eight of the subjects (mean ventrodorsal difference 0.39, range 0.19-0.90), whereas two showed a clear increase toward dependent lung regions (range 0.16-0.26). Seven of the subjects with a falling ventrodorsal V/Q gradient also exhibited discrete regions of low V/Q at the dorsal lung border. We conclude that, in normal subjects, ventilation and perfusion are generally well matched in the supine posture, but isolated mismatching often occurs in dependent lung regions.     

High oxygen concentrations predispose mouse lungs to the deleterious effects of high stretch ventilation.

Mechanical ventilation is a necessary intervention for patients with acute lung injury. However, mechanical ventilation can propagate acute lung injury and increase systemic inflammation. The exposure to >21% oxygen is often associated with mechanical ventilation yet has not been examined within the context of lung stretch. We hypothesized that mice exposed to >90% oxygen will be more susceptible to the deleterious effects of high stretch mechanical ventilation. C57B1/6 mice were randomized into 48-h exposure of 21 or >90% oxygen; mice were then killed, and isolated lungs were randomized into a nonstretch or an ex vivo, high-stretch mechanical ventilation group. Lungs were assessed for compliance and lavaged for surfactant analysis, and cytokine measurements or lungs were homogenized for surfactant-associated protein analysis. Mice exposed to >90% oxygen + stretch had significantly lower compliance, altered pulmonary surfactant, and increased inflammatory cytokines compared with all other groups. Our conclusion is that 48 h of >90% oxygen and high-stretch mechanical ventilation deleteriously affect lung function to a greater degree than stretch alone.     

Mechanisms of recruitment in oleic acid-injured lungs.

Lung recruitment strategies, such as the application of positive end-expiratory pressure (PEEP), are thought to protect the lungs from ventilator-associated injury by reducing the shear stress associated with the repeated opening of collapsed peripheral units. Using the parenchymal marker technique, we measured regional lung deformations in 13 oleic acid (OA)-injured dogs during mechanical ventilation in different postures. Whereas OA injury caused a marked decrease in the oscillation amplitude of dependent lung regions, even the most dependent regions maintained normal end-expiratory dimensions. This is because dependent lung is flooded as opposed to collapsed. PEEP restored oscillation amplitudes only at pressures that raised regional volumes above preinjury levels. Because the amount of PEEP necessary to promote dependent lung recruitment increased the end-expiratory dimensions of all lung regions (nondependent AND dependent ones) compared with their preinjury baseline, the "price" for recruitment is a universal increase in parenchymal stress. We conclude that the mechanics of the OA-injured lung might be more appropriately viewed as a partial liquid ventilation problem and not a shear stress and airway collapse problem and that the mechanisms of PEEP-related lung protection might have to be rethought.     

Topographical distribution of pulmonary perfusion and ventilation, assessed by PET in supine and prone humans.

Using positron emission tomography (PET) and intravenously injected (13)N(2), we assessed the topographical distribution of pulmonary perfusion (Q) and ventilation (V) in six healthy, spontaneously breathing subjects in the supine and prone position. In this technique, the intrapulmonary distribution of (13)N(2), measured during a short apnea, is proportional to regional Q. After resumption of breathing, regional specific alveolar V (sVA, ventilation per unit of alveolar gas volume) can be calculated from the tracer washout rate. The PET scanner imaged 15 contiguous, 6-mm-thick, slices of lung. Vertical gradients of Q and sVA were computed by linear regression, and spatial heterogeneity was assessed from the squared coefficient of variation (CV(2)). Both CV and CV were corrected for the estimated contribution of random imaging noise. We found that 1) both Q and V had vertical gradients favoring dependent lung regions, 2) vertical gradients were similar in the supine and prone position and explained, on average, 24% of Q heterogeneity and 8% of V heterogeneity, 3) CV was similar in the supine and prone position, and 4) CV was lower in the prone position. We conclude that, in recumbent, spontaneously breathing humans, 1) vertical gradients favoring dependent lung regions explain a significant fraction of heterogeneity, especially of Q, and 2) although Q does not seem to be systematically more homogeneous in the prone position, differences in individual behaviors may make the prone position advantageous, in terms of V-to-Q matching, in selected subjects.     

Lung regional stress and strain as a function of posture and ventilatory mode

During positive-pressure ventilation parenchymal deformation can be assessed as strain (volume increase above functional residual capacity) in response to stress (transpulmonary pressure). The aim of this study was to explore the relationship between stress and strain on the regional level using computed tomography in anesthetized healthy pigs in two postures and two patterns of breathing. Airway opening and esophageal pressures were used to calculate stress; change of gas content as assessed from computed tomography was used to calculate strain. Static stress-strain curves and dynamic strain-time curves were constructed, the latter during the inspiratory phase of volume and pressure-controlled ventilation, both in supine and prone position. The lung was divided into nondependent, intermediate, dependent, and central regions: their curves were modeled by exponential regression and examined for statistically significant differences. In all the examined regions, there were strong but different exponential relations between stress and strain. During mechanical ventilation, the end-inspiratory strain was higher in the dependent than in the nondependent regions. No differences between volume- and pressure-controlled ventilation were found. However, during volume control ventilation, prone positioning decreased the end-inspiratory strain of dependent regions and increased it in nondependent regions, resulting in reduced strain gradient. Strain is inhomogeneously distributed within the healthy lung. Prone positioning attenuates differences between dependent and nondependent regions. The regional effects of ventilatory mode and body positioning should be further explored in patients with acute lung injury.     

3He MRI-based assessment of posture-dependent regional ventilation gradients in rats.

A recently developed method for quantitative assessment of regional lung ventilation was employed for the study of posture-dependent ventilation differences in rats. The measurement employed hyperpolarized (3)He MRI to detect the build-up of the signal intensity after increasing numbers of (3)He breaths, which allowed for computation of a regional ventilation parameter. A group of six anesthetized rats was studied in both supine and prone postures. Three-dimensional maps of the ventilation parameter were obtained with high spatial resolution (voxel volume approximately 2 mm(3)). Vertical (dorsal-ventral) gradients of the ventilation index, defined as the regional ventilation normalized by the average ventilation within the whole lung, were investigated. Variations in the regional distribution of the ventilation parameter, as well as of the ventilation index, could be detected, depending on the posture of the rats. In supine posture, ventilation was elevated in the dependent parts of the lungs, with a linear gradient of the ventilation index of -0.11 +/- 0.03 cm(-1). In prone posture, the distribution of ventilation was more uniform, with a significantly (P < 0.001) smaller gradient of the ventilation index of -0.01 +/- 0.02 cm(-1). It is concluded that the (3)He MRI-based method can detect and quantify regional ventilation gradients in animals as small as the rat and that these gradients depend on prone or supine posture of the animal.     

Effect of mean airway pressure on gas exchange during high-frequency oscillatory ventilation

We studied the effect of mean airway pressure (Paw) on gas exchange during high-frequency oscillatory ventilation in 14 adult rabbits before and after pulmonary saline lavage. Sinusoidal volume changes were delivered through a tracheostomy at 16 Hz, a tidal volume of 1 or 2 ml/kg, and inspired O2 fraction of 0.5. Arterial PO2 and PCO2 (PaO2, PaCO2), lung volume change, and venous admixture were measured at Paw from 5 to 25 cmH2O after either deflation from total lung capacity or inflation from relaxation volume (Vr). The rabbits were lavaged with saline until PaO2 was less than 70 Torr, and all measurements were repeated. Lung volume change was measured in a pressure plethysmograph. Raising Paw from 5 to 25 cmH2O increased lung volume by 48-50 ml above Vr in both healthy and lavaged rabbits. Before lavage, PaO2 was relatively insensitive to changes in Paw, but after lavage PaO2 increased with Paw from 42.8 +/- 7.8 to 137.3 +/- 18.3 (SE) Torr (P less than 0.001). PaCO2 was insensitive to Paw change before and after lavage. At each Paw after lavage, lung volume was larger, venous admixture smaller, and PaO2 higher after deflation from total lung capacity than after inflation from Vr. This study shows that the effect of increased Paw on PaO2 is mediated through an increase in lung volume. In saline-lavaged lungs, equal distending pressures do not necessarily imply equal lung volumes and thus do not imply equal PaO2.     

Novel positron emission tomography/computed tomography of diffuse parenchymal lung disease combining a labeled somatostatin receptor analogue and 2-deoxy-2[18F]fluoro-D-glucose

We prospectively investigated the potential of positron emission tomography (PET) using the somatostatin receptor (SSTR) analogue ??Ga-DOTATATE and 2-deoxy-2[1?F]fluoro-D-glucose (1?F-FDG) in diffuse parenchymal lung disease (DPLD). Twenty-six patients (mean age 68.9 ± 11.0 years) with DPLD were recruited for ??Ga-DOTATATE and 1?F-FDG combined PET/high-resolution computed tomography (HRCT) studies. Ten patients had idiopathic pulmonary fibrosis (IPF), 12 patients had nonspecific interstitial pneumonia (NSIP), and 4 patients had other forms of DPLD. Using PET, the pulmonary tracer uptake (maximum standardized uptake value [SUV(max)]) was calculated. The distribution of PET tracer was compared to the distribution of lung parenchymal changes on HRCT. All patients demonstrated increased pulmonary PET signal with ??Ga-DOTATATE and 1?F-FDG. The distribution of parenchymal uptake was similar, with both tracers corresponding to the distribution of HRCT changes. The mean SUV(max) was 2.2 ± 0.7 for ??Ga-DOTATATE and 2.8 ± 1.0 (t-test, p = .018) for 1?F-FDG. The mean ??Ga-DOTATATE SUV(max) in IPF patients was 2.5 ± 0.9, whereas it was 2.0 ± 0.7 (p = .235) in NSIP patients. The correlation between ??Ga-DOTATATE SUV(max) and gas transfer (transfer factor of the lung for carbon monoxide [TLCO]) was r = -.34 (p = .127) and r = -.49 (p = .028) between 1?F-FDG SUV(max) and TLCO. We provide noninvasive in vivo evidence in humans showing that SSTRs may be detected in the lungs of patients with DPLD in a similar distribution to sites of increased uptake of 1?F-FDG on PET.     

Spatial distribution of ventilation and perfusion in anesthetized dogs in lateral postures.

We aimed to assess the influence of lateral decubitus postures and positive end-expiratory pressure (PEEP) on the regional distribution of ventilation and perfusion. We measured regional ventilation (VA) and regional blood flow (Q) in six anesthetized, mechanically ventilated dogs in the left (LLD) and right lateral decubitus (RLD) postures with and without 10 cmH(2)O PEEP. Q was measured by use of intravenously injected 15-microm fluorescent microspheres, and VA was measured by aerosolized 1-microm fluorescent microspheres. Fluorescence was analyzed in lung pieces approximately 1.7 cm(3) in volume. Multiple linear regression analysis was used to evaluate three-dimensional spatial gradients of Q, VA, the ratio VA/Q, and regional PO(2) (Pr(O(2))) in both lungs. In the LLD posture, a gravity-dependent vertical gradient in Q was observed in both lungs in conjunction with a reduced blood flow and Pr(O(2)) to the dependent left lung. Change from the LLD to the RLD or 10 cmH(2)O PEEP increased local VA/Q and Pr(O(2)) in the left lung and minimized any role of hypoxia. The greatest reduction in individual lung volume occurred to the left lung in the LLD posture. We conclude that lung distortion caused by the weight of the heart and abdomen is greater in the LLD posture and influences both Q and VA, and ultimately gas exchange. In this respect, the smaller left lung was the most susceptible to impaired gas exchange in the LLD posture.     

Mechanics of edematous lungs.

Using the parenchymal marker technique, we measured pressure (P)-volume (P-V) curves of regions with volumes of approximately 1 cm3 in the dependent caudal lobes of oleic acid-injured dog lungs, during a very slow inflation from P = 0 to P = 30 cmH2O. The regional P-V curves are strongly sigmoidal. Regional volume, as a fraction of volume at total lung capacity, remains constant at 0.4-0.5 for airway P values from 0 to approximately 20 cmH2O and then increases rapidly, but continuously, to 1 at P = approximately 25 cmH2O. A model of parenchymal mechanics was modified to include the effects of elevated surface tension and fluid in the alveolar spaces. P-V curves calculated from the model are similar to the measured P-V curves. At lower lung volumes, P increases rapidly with lung volume as the air-fluid interface penetrates the mouth of the alveolus. At a value of P = approximately 20 cmH2O, the air-fluid interface is inside the alveolus and the lung is compliant, like an air-filled lung with constant surface tension. We conclude that the properties of the P-V curve of edematous lungs, particularly the knee in the P-V curve, are the result of the mechanics of parenchyma with constant surface tension and partially fluid-filled alveoli, not the result of abrupt opening of airways or atelectatic parenchyma.     

Chest wall restriction limits high airway pressure-induced lung injury in young rabbits

High peak inspiratory pressures (PIP) during mechanical ventilation can induce lung injury. In the present study we compare the respective roles of high tidal volume with high PIP in intact immature rabbits to determine whether the increase in capillary permeability is the result of overdistension of the lung or direct pressure effects. New Zealand White rabbits were assigned to one of three protocols, which produced different degrees of inspiratory volume limitation: intact closed-chest animals (CC), closed-chest animals with a full-body plaster cast (C), and isolated excised lungs (IL). The intact animals were ventilated at 15, 30, or 45 cmH2O PIP for 1 h, and the lungs of the CC and C groups were placed in an isolated lung perfusion system. Microvascular permeability was evaluated using the capillary filtration coefficient (Kfc). Base-line Kfc for isolated lungs before ventilation was 0.33 +/- 0.31 ml.min-1.cmH2O-1.100g-1 and was not different from the Kfc in the CC group ventilated with 15 cmH2O PIP. Kfc increased by 850% after ventilation with only 15 cmH2O PIP in the unrestricted IL group, and in the CC group Kfc increased by 31% after 30 cmH2O PIP and 430% after 45 cmH2O PIP. Inspiratory volume limitation by the plaster cast in the C group prevented any significant increase in Kfc at the PIP values used. These data indicate that volume distension of the lung rather than high PIP per se produces microvascular damage in the immature rabbit lung.     

Regional VA, Q, and VA/Q during PLV: effects of nitroprusside and inhaled nitric oxide.

Partial liquid ventilation (PLV) with high-specific-weight perfluorocarbon liquids has been shown to improve oxygenation in acute lung injury, possibly by redistributing perfusion from dependent, injured regions to nondependent, less injured regions of the lung. Our hypothesis was that during PLV in normal lungs, a shift in perfusion away from dependent lung zones might, in part, be due to vasoconstriction that could be reversed by infusing sodium nitroprusside (NTP). In addition, delivering inhaled NO during PLV should improve gas exchange by further redistributing blood flow to well-ventilated lung regions. To examine this, we used a single transverse-slice positron emission tomography camera to image regional ventilation and perfusion at the level of the heart apex in six supine mechanically ventilated sheep during five conditions: control, PLV, PLV + NTP, and PLV + NO at 10 and 80 ppm. We found that PLV shifted perfusion from dependent to middle regions, and the dependent region demonstrated marked hypoventilation. The vertical distribution of perfusion changed little when high-dose intravenous NTP was added during PLV, and inhaled NO tended to shift perfusion toward better ventilated middle regions. We conclude that PLV shifts perfusion to the middle regions of the lung because of the high specific weight of perflubron rather than vasoconstriction.     

Effect of increased surface tension and assisted ventilation on 99mTc-DTPA clearance

Experiments were performed to determine the effects of conventional mechanical ventilation (CMV) and high-frequency oscillation (HFO) on the clearance of technetium-99m-labeled diethylenetriamine pentaacetate (99mTc-DTPA) from lungs with altered surface tension properties. A submicronic aerosol of 99mTc-DTPA was insufflated into the lungs of anesthetized, tracheotomized rabbits before and 1 h after the administration of the aerosolized detergent dioctyl sodium sulfosuccinate (OT). Rabbits were ventilated by one of four methods: 1) spontaneous breathing; 2) CMV at 12 cmH2O mean airway pressure (MAP); 3) HFO at 12 cmH2O MAP; 4) HFO at 16 cmH2O MAP. Administration of OT resulted in decreased arterial PO2 (PaO2), increased lung wet-to-dry weight ratios, and abnormal lung pressure-volume relationships, compatible with increased surface tension. 99mTc-DTPA clearance was accelerated after OT in all groups. The post-OT rate of clearance (k) was significantly faster (P less than 0.05) in the CMV at 12 cmH2O MAP [k = 7.57 +/- 0.71%/min (SE)] and HFO at 16 cmH2O MAP (k = 6.92 +/- 0.61%/min) groups than in the spontaneously breathing (k = 4.32 +/- 0.55%/min) and HFO at 12 cmH2O MAP (4.68 +/- 0.63%/min) groups. The clearance curves were biexponential in the former two groups. We conclude that pulmonary clearance of 99mTc-DTPA is accelerated in high surface tension pulmonary edema, and this effect is enhanced by both conventional ventilation and HFO at high mean airway pressure.     

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.     

Regional ventilation-perfusion distribution is more uniform in the prone position.

The arterial blood PO(2) is increased in the prone position in animals and humans because of an improvement in ventilation (VA) and perfusion (Q) matching. However, the mechanism of improved VA/Q is unknown. This experiment measured regional VA/Q heterogeneity and the correlation between VA and Q in supine and prone positions in pigs. Eight ketamine-diazepam-anesthetized, mechanically ventilated pigs were studied in supine and prone positions in random order. Regional VA and Q were measured using fluorescent-labeled aerosols and radioactive-labeled microspheres, respectively. The lungs were dried at total lung capacity and cubed into 603-967 small ( approximately 1.7-cm(3)) pieces. In the prone position the homogeneity of the ventilation distribution increased (P = 0.030) and the correlation between VA and Q increased (correlation coefficient = 0.72 +/- 0.08 and 0.82 +/- 0.06 in supine and prone positions, respectively, P = 0.03). The homogeneity of the VA/Q distribution increased in the prone position (P = 0.028). We conclude that the improvement in VA/Q matching in the prone position is secondary to increased homogeneity of the VA distribution and increased correlation of regional VA and Q.