Dorsal recruitment with flow-controlled expiration (FLEX): an experimental study in mechanically ventilated lung-healthy and lung-injured pigs.

BACKGROUND: Concepts for optimizing mechanical ventilation focus mainly on modifying the inspiratory phase. We propose flow-controlled expiration (FLEX) as an additional means for lung protective ventilation and hypothesize that it is capable of recruiting dependent areas of the lungs. This study investigates potential recruiting effects of FLEX using models of mechanically ventilated pigs before and after induction of lung injury with oleic acid. METHODS: Seven pigs in the supine position were ventilated with tidal volume 8 ml·kg- 1 and positive end-expiratory pressure (PEEP) set to maintain partial pressure of oxygen in arterial blood (paO2) at ≥ 60 mmHg and monitored with electrical impedance tomography (EIT). Two ventilation sequences were recorded - one before and one after induction of lung injury. Each sequence comprised 2 min of conventional volume-controlled ventilation (VCV), 2 min of VCV with FLEX and 1 min again of conventional VCV. Analysis of the EIT recordings comprised global and ventral and dorsal baseline levels of impedance curves, end-expiratory no-flow periods, tidal variation in ventral and dorsal areas, and regional ventilation delay index. RESULTS: With FLEX, the duration of the end-expiratory zero flow intervals was significantly shortened (VCV 1.4 ± 0.3 s; FLEX 0.7 ± 0.1 s, p < 0.001), functional residual capacity was significantly elevated in both conditions of the lungs (global: healthy, increase of 87 ± 12 ml, p < 0.001; injured, increase of 115 ± 44 ml, p < 0.001; ventral: healthy, increase of 64 ± 11 ml, p < 0.001; injured, increase of 83 ± 22 ml, p < 0.001; dorsal: healthy, increase of 23 ± 5 ml, p < 0.001; injured, increase of 32 ± 26 ml, p = 0.02), and ventilation was shifted from ventral to dorsal areas (dorsal increase: healthy, 1 ± 0.5%, p < 0.01; dorsal increase: injured, 6 ± 2%, p < 0.01), compared to conventional VCV. Recruiting effects of FLEX persisted during conventional VCV following FLEX ventilation mostly in the injured but also in the healthy lungs. CONCLUSIONS: FLEX shifts regional ventilation towards dependent lung areas in healthy and in injured pig lungs. The recruiting capabilities of FLEX may be mainly responsible for lung-protective effects observed in an earlier study.

Optical clearing: impact of optical and dielectric properties of clearing solutions on pulmonary tissue mechanics.

Optical clearing allows tissue visualization under preservation of organ integrity. Optical clearing of organs with a physiological change in three-dimensional geometry (such as the lung) would additionally allow visualization of macroscopic and microscopic tissue geometry. A prerequisite, however, is the preservation of the native tissue mechanics of the optically cleared lung tissue. We investigated the impact of optical and dielectric properties of clearing solutions on biomechanics and clearing potency in porcine tissue strips of healthy lungs. After fixation, bleaching, and rehydration, four methods of optical clearing were investigated using eight different protocols. The mechanical and optical properties of the cleared lung tissue strips were investigated by uniaxial tensile testing and by analyzing optical transparency and translucency for red, green, and blue light before, during, and after the biochemical optical clearing process. Fresh tissue strips were used as controls. Best balance between efficient clearing and preserved mechanics was found for clearing with a 1:1 mixture of dimethyl sulfoxide (DMSO) and aniline. Our findings show that 1) the degree of tissue transparency and translucency correlated with the refractive index of the clearing solution index (r = 0.976, P = 0.0004; and r = 0.91, P = 0.0046, respectively), 2) tissue mechanics were affected by dehydration and the type of clearing solution, and 3) tissue biomechanics and geometry correlated with the dielectric constant of the clearing solution (r = -0.98, P < 0.00001; and r = 0.69, P = 0.013, respectively). We show that the lower the dielectric constant of the clearing solutions, the larger the effect on tissue stiffness. This suggests that the dielectric constant is an important measure in determining the effect of a clearing solution on lung tissue biomechanics. Optimal tissue transparency requires complete tissue dehydration and a refractive index of 1.55 of the clearing solution.NEW & NOTEWORTHY Investigating optical clearing in porcine lung tissue strips, we found that refractive index and dielectric constant of the clearing solution affected tissue clearing and biomechanics. By documenting the impact of the composition of the clearing solution on clearing potency and preservation of tissue mechanics, our results help to compose optimal clearing solutions. In addition, the results allow conclusions on the molecular interaction of solvents with collagen fibers in tissue, thereby consolidating existing theories about the functionality of collagen.

The Equilibration of PCO2 in Pigs Is Independent of Lung Injury and Hemodynamics.

OBJECTIVES: In mechanical ventilation, normoventilation in terms of PCO2 can be achieved by titration of the respiratory rate and/or tidal volume. Although a linear relationship has been found between changes in respiratory rate and resulting changes in end-tidal cO2 (△PetCO2) as well as between changes in respiratory rate and equilibration time (teq) for mechanically ventilated patients without lung injury, it is unclear whether a similar relationship holds for acute lung injury or altered hemodynamics. DESIGN: We performed a prospective randomized controlled animal study of the change in PetCO2 with changes in respiratory rate in a lung-healthy, lung-injury, lung-healthy + altered hemodynamics, and lung-injury + altered hemodynamics pig model. SETTING: University research laboratory. SUBJECTS: Twenty mechanically ventilated pigs. INTERVENTIONS: Moderate lung injury was induced by injection of oleic acid in 10 randomly assigned pigs, and after the first round of measurements, cardiac output was increased by approximately 30% by constant administration of noradrenalin in both groups. MEASUREMENTS AND MAIN RESULTS: We systematically increased and decreased changes in respiratory rate according to a set protocol: +2, -4, +6, -8, +10, -12, +14 breaths/min and awaited equilibration of Petco2. We found a linear relationship between changes in respiratory rate and △PetCO2 as well as between changes in respiratory rate and teq. A two-sample t test resulted in no significant differences between the lung injury and healthy control group before or after hemodynamic intervention. Furthermore, exponential extrapolation allowed prediction of the new PetCO2 equilibrium and teq after 5.7 ± 5.6 min. CONCLUSIONS: The transition between PetCO2 equilibria after changes in respiratory rate might not be dependent on moderate lung injury or cardiac output but on the metabolic production or capacity of cO2 stores. Linear relationships previously found for lung-healthy patients and early prediction of PetCO2 equilibration could therefore also be used for the titration of respiratory rate on the PetCO2 for a wider range of pathologies by the physician or an automated ventilation system.

Simultaneous monitoring of intratidal compliance and resistance in mechanically ventilated piglets: A feasibility study in two different study groups.

Compliance measures the force counteracting parenchymal lung distension. In mechanical ventilation, intratidal compliance-volume (C(V))-profiles therefore change depending on PEEP, tidal volume (VT), and underlying mechanical lung properties. Resistance counteracts gas flow through the airways. Due to anatomical linking between parenchyma and airways, intratidal resistance-volume (R(V))-profiles are hypothesised to change in a non-linear way as well. We analysed respiratory system mechanics in fifteen piglets with lavage-induced lung injury and nine healthy piglets ventilated at different PEEP/VT-settings. In healthy lungs, R(V)-profiles remained mostly constant and linear at all PEEP-settings whereas the shape of the C(V)-profiles showed an increase toward a maximum followed by a decrease (small PEEP) or volume-dependent decrease (large PEEP). In the lavage group, a large drop in resistance at small volumes and slow decrease toward larger volumes was found for small PEEP/VT-settings where C(V)-profiles revealed a volume-dependent increase (small PEEP) or a decrease (large PEEP and large VT). R(V)-profiles depend characteristically on PEEP, VT, and possibly whether lungs are healthy or not. Curved R(V)-profiles might indicate pathological changes in the underlying mechanical lung properties and/or might be a sign of derecruitment.

The pressure drop across the endotracheal tube in mechanically ventilated pediatric patients.

BACKGROUND: During mechanical ventilation, the airway pressure (Paw) is usually monitored. However, Paw comprises the endotracheal tube (ETT)-related pressure drop (∆PETT ) and thus does not reflect the pressure in the patients' lungs. Therefore, monitoring of mechanical ventilation should be based on the tracheal pressure (Ptrach ). We systematically investigated potential factors influencing ∆PETT in pediatric ETTs. METHODS: In this study, the flow-dependent pressure drop across pediatric ETTs from four manufacturers [2.0-4.5 mm inner diameter (ID)] was estimated in a physical model of the upper airways. Additionally, ∆PETT was examined with the ETTs shortened to 75% of their original length and at different curvatures. In nine healthy mechanically ventilated children (aged between 9 days and 29 months), Ptrach was compared to Paw . RESULTS: ∆PETT was nonlinearly flow dependent. Low IDs corresponded to high ∆PETT . Differences between ETTs from different manufacturers were identified. Shortening of the ETTs' length by 25% reduced ∆PETT on average by 14% of the value at original length. Ventilation frequency and tube curvature did not influence ∆PETT to a relevant extent. In the pediatric patients, the root mean square deviation between Paw and Ptrach was 2.3 cm H2O. CONCLUSION: Paw and Ptrach differ considerably (by ∆PETT ) during mechanical ventilation of pediatric patients. The ETTs' ID, tube length, and manufacturer type are significant factors for ∆PETT and should be taken into account when Paw is valuated. For this purpose, Ptrach can be continuously calculated with good precision by means of the Rohrer approximation.

Mechanical load and mechanical integrity of lung cells - experimental mechanostimulation of epithelial cell- and fibroblast-monolayers.

Experimental mechanostimulation of soft biologic tissue is widely used to investigate cellular responses to mechanical stress or strain. Reactions on mechanostimulation are investigated in terms of morphological changes, inflammatory responses and apoptosis/necrosis induction on a cellular level. In this context, the analysis of the mechanical characteristics of cell-layers might allow to indicate patho-physiological changes in the cell-cell contacts. Recently, we described a device for experimental mechanostimulation that allows simultaneous measurement of the mechanical characteristics of cell-monolayers. Here, we investigated how cultivated lung epithelial cell- and fibroblast-monolayers behave mechanically under different amplitudes of biaxial distension. The cell monolayers were sinusoidally deflected to 5%, 10% or 20% surface gain and their mechanical properties during mechanostimulation were analyzed. With increasing stimulation amplitudes more pronounced reductions of cell junctions were observed. These findings were accompanied by a substantial loss of monolayer rigidity. Pulmonary fibroblast monolayers were initially stiffer but were stronger effected by the mechanostimulation compared to epithelial cell-monolayers. We conclude that, according to their biomechanical function within the pulmonary tissue, epithelial cells and fibroblasts differ with respect to their mechanical characteristics and tolerance of mechanical load.

Flow Controlled Expiration is perceived as less uncomfortable than positive end expiratory pressure.

Recently, we presented Flow Controlled Expiration (FLEX) as a new option for lung-protective ventilation. FLEX delays the expiratory volume decrease in the lungs without prolonging the duration of expiration. Most ventilated patients nowadays receive spontaneous breathing support. We investigated whether FLEX is tolerated by awake subjects. In 24 healthy subjects restrictive lung disease was simulated by bandaging the thorax. The subjects were asked to indicate the perceived discomfort of breathing at various levels of positive end expiratory pressure (PEEP=0, 3, 6 or 9 cmH2O) with and without FLEX. Breathing discomfort was not affected by FLEX (p=0.269), but higher PEEP increased breathing discomfort (p<0.001). Only in forced choice comparison a stronger FLEX condition was perceived as less comfortable (p<0.01) than a weaker one. We conclude that FLEX decreases the breathing comfort in healthy subjects to a lesser extent than PEEP. Therefore, FLEX might be used to support ventilation therapy in spontaneously breathing patients.

Endomicroscopic analysis of time- and pressure-dependent area of subpleural alveoli in mechanically ventilated rats.

We investigated the effects of recruitment maneuvers on subpleural alveolar area in healthy rats. 36 mechanically ventilated rats were allocated to either ZEEP-group or PEEP - 5cmH2O - group. The subpleural alveoli were observed using a transthoracal endoscopic imaging technique. Two consecutive low-flow maneuvers up to 30cmH2O peak pressure each were performed, interrupted by 5s plateau phases at four different pressure levels. Alveolar area change at maneuver peak pressures and during the plateau phases was calculated and respiratory system compliance before and after the maneuvers was analyzed. In both groups alveolar area at the second peak of the maneuver did not differ significantly compared to the first peak. During the plateau phases there was a slight increase in alveolar area. After the maneuvers, compliance increased by 30% in ZEEP group and 20% in PEEP group. We conclude that the volume insufflated by the low-flow recruitment maneuver is distributed to deeper but not to subpleural lung regions.

Breathing-phase selective filtering of respiratory data improves analysis of dynamic respiratory mechanics.

BACKGROUND: The analysis of non-linear respiratory system mechanics under the dynamic conditions of controlled mechanical ventilation is affected by systemic disturbances of the respiratory signals. Cardio-pulmonary coupling induces cardiogenic oscillations to the respiratory signals, which appear prominently in the second half of expiration. OBJECTIVE: We hypothesized that breathing phase-selective filtering of expiratory data improves the analysis of respiratory system mechanics. METHODS: We retrospectively analyzed data from a multicenter-study (28 patients with injured lungs, under volume-controlled ventilation) and from two additional studies (3 lung healthy patients and 3 with injured lungs, under pressure-controlled ventilation). Data streams were recorded at different levels of positive end-expiratory pressure. Using the gliding-SLICE method, intratidal dynamic respiratory mechanics were analyzed with and without low-pass filtering of expiratory or inspiratory data separately. The quality of data analysis was derived from the coefficient of determination R^2. RESULTS: Without filtering, R^2 lay below 0.995 for 87 of 280 investigated data streams. In 68 cases expiration-selective low-pass filtering improved the quality of analysis to R^2 ⩾ 0.995. In contrast, inspiration-selective filtering did not improve R^2. CONCLUSIONS: The selective filtering of expiration data eliminates negative side-effects of cardiogenic oscillations thus leading to a significant improvement of the analysis of dynamic respiratory system mechanics.

Assessing respiratory function depends on mechanical characteristics of balloon catheters.

BACKGROUND: Respiratory muscle function and lung and chest wall mechanics are reliably assessed by esophageal and gastric balloon catheters. The aim of this in vitro bench study was to assess the mechanical properties of commercially available balloon catheters using an experimental model with 3 defined compliances (27, 54, 90 mL/cm H2O). METHODS: Six catheters were investigated in 4 conditions: (1) balloon pressure during initial inflation, (2) static pressure measurements at different filling volumes, (3) estimation of set compliances in the experimental lung model at different levels of superimposed pressure, and (4) elastic balloon properties after 16 h of inflation. RESULTS: 5/6 catheters showed initial pressure artifacts resulting from material adhesion. All static pressure measurements could be performed with an error < 1 cm H2O. Balloon overfilling resulted in larger errors in 4/6 catheters. Compliance determined from pressure measurements via the catheters differed by < 5% from that determined from direct pressure measurements. Sixteen hours of inflation resulted in a broader working range, that is, overfilling effects occurred at higher filling volumes. CONCLUSIONS: The reliability of pressure measurements and estimation of the lung model's compliance in the tested catheters are high. Filling volume appears to be critical for precise pressure measurement and compliance estimation. At first use, adhesion of the balloon material might prevent reliable pressure measurement.

The dynamics of carbon dioxide equilibration after alterations in the respiratory rate.

Manual or automated control of mechanical ventilation can be realized as an open or closed-loop system for which the regulation of the ventilation parameters ideally is tuned to the dynamics and equilibration time of the biological system. We investigated the dynamic, transient state and equilibration time (teq) of the CO2 partial pressure (PCO2) after changes in the respiratory rate (RR). In 17 anaesthetized patients without known history of lung disease, respiratory rate was alternately increased and decreased and end-tidal CO2 partial pressures (PetCO2) were measured. Linear relations were found between ΔRR and PetCO2 changes (ΔPetCO2 = 0.3 − 1.1 ΔRR) and between ΔRR and teq for increasing and decreasing RR (teq(hypervent) = 0.5 |ΔRR|, teq(hypovent) = 0.7 |ΔRR|). Extrapolation of the transition between two PCO2 steady-states allowed for the prediction of the new PCO2 steady-state as early as 0.5 teq with an error <4 mmHg. At bedside or in automated ventilation systems, the linear dependencies between ΔRR and ΔPCO2 and between ΔRR and teq as well as early steady-state prediction of PCO2 could be used as a guidance towards a timing and step size regulation of RR that is well adapted to the biological system.

Time and volume dependence of dead space in healthy and surfactant-depleted rat lungs during spontaneous breathing and mechanical ventilation.

Volumetric capnography is a standard method to determine pulmonary dead space. Hereby, measured carbon dioxide (CO2) in exhaled gas volume is analyzed using the single-breath diagram for CO2. Unfortunately, most existing CO2 sensors do not work with the low tidal volumes found in small animals. Therefore, in this study, we developed a new mainstream capnograph designed for the utilization in small animals like rats. The sensor was used for determination of dead space volume in healthy and surfactant-depleted rats (n = 62) during spontaneous breathing (SB) and mechanical ventilation (MV) at three different tidal volumes: 5, 8, and 11 ml/kg. Absolute dead space and wasted ventilation (dead space volume in relation to tidal volume) were determined over a period of 1 h. Dead space increase and reversibility of the increase was investigated during MV with different tidal volumes and during SB. During SB, the dead space volume was 0.21 ± 0.14 ml and increased significantly at MV to 0.39 ± 0.03 ml at a tidal volume of 5 ml/kg and to 0.6 ± 0.08 ml at a tidal volume of 8 and 11 ml/kg. Dead space and wasted ventilation during MV increased with tidal volume. This increase was mostly reversible by switching back to SB. Surfactant depletion had no further influence on the dead space increase during MV, but impaired the reversibility of the dead space increase.

A method to measure mechanical properties of pulmonary epithelial cell layers.

The lung has a huge inner alveolar surface composed of epithelial cell layers. The knowledge about mechanical properties of lung epithelia is helpful to understand the complex lung mechanics and biomechanical interactions. Methods have been developed to determine mechanical indices (e.g., tissue elasticity) which are both very complex and in need of costly equipment. Therefore, in this study, a mechanostimulator is presented to dynamically stimulate lung epithelial cell monolayers in order to determine their mechanical properties based on a simple mathematical model. First, the method was evaluated by comparison to classical tensile testing using silicone membranes as substitute for biological tissue. Second, human pulmonary epithelial cells (A549 cell line) were grown on flexible silicone membranes and stretched at a defined magnitude. Equal secant moduli were determined in the mechanostimulator and in a conventional tension testing machine (0.49 ± 0.05 MPa and 0.51 ± 0.03 MPa, respectively). The elasticity of the cell monolayer could be calculated by the volume-pressure relationship resulting from inflation of the membrane-cell construct. The secant modulus of the A549 cell layer was calculated as 0.04 ± 0.008 MPa. These findings suggest that the mechanostimulator may represent an adequate device to determine mechanical properties of cell layers.

Endoscopic imaging to assess alveolar mechanics during quasi-static and dynamic ventilatory conditions in rats with noninjured and injured lungs.

OBJECTIVES: Although global respiratory mechanics are usually used to determine the settings of mechanical ventilation, this approach does not adequately take into account alveolar mechanics. However, it should be expected that the ventilatory condition (quasi-static vs. dynamic) and lung condition (noninjured vs. injured) affect alveolar mechanics in a clinically relevant way. Accordingly, the aim of this study was to investigate alveolar mechanics during quasi-static and dynamic ventilatory maneuvers in noninjured and injured lungs. We hypothesized that alveolar mechanics vary with ventilatory and lung conditions. DESIGN: Prospective animal study. SETTING: Animal research laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Alveolar mechanics (derived from alveolar size and airway pressure) were determined in noninjured (n = 9) and in lungs lavaged with saline (n = 8) at quasi-static (low flow at a peak pressure of 40 cm H2O) and dynamic ventilatory maneuvers (increase and decrease in positive end-expiratory pressure from 0 to 15 and back to 0 cm H2O in steps of 3 cm H2O). Alveoli were recorded endoscopically and alveolar mechanics were extracted using automated tracking of alveolar contours. MEASUREMENTS AND MAIN RESULTS: The increase in alveolar size during quasi-static maneuvers was significantly greater than during dynamic maneuvers in noninjured (mean difference 18%, p < 0.001) but not in injured lungs (mean difference 3%, p = 0.293). During dynamic maneuvers, slope of the intratidal alveolar pressure/area curve (reflecting distensibility) decreased with increasing positive end-expiratory pressure (p = 0.001) independent of lung condition (noninjured and injured lungs). In contrast, independent of positive end-expiratory pressure but dependent on lung condition, the maximal tidal change in alveolar size was greater by an average of 40% in injured compared with noninjured lungs (p = 0.028). CONCLUSIONS: Alveolar mechanics during mechanical ventilation differed between quasi-static and dynamic conditions and varied with lung condition. Our data thus confirm that analysis of respiratory system mechanics under dynamic conditions is preferable to analysis during static conditions.

Time-dependent recruitment effects in ventilated healthy and lung-injured rats: "recruitment-memory".

We investigated the sustained effects of recruitment manoeuvres in terms of "recruitment memory" in healthy and lung injured rats. 46 ventilated rats were allocated to either the control (sham) or the lavage group. Two consecutive low-flow manoeuvres were performed before sham/lavage and hourly during a 2-h-observation period. The slopes of the inspiratory limbs of the two resulting pressure-volume loops were translated into compliance-volume curves. The difference between the two compliance curves was smaller after lavage (root-mean-square deviation: 0.065 ml/cm H2O control group, 0.038 ml/cm H2O lavage group; p<0.05) and stayed small during the whole experiment. In the control group, the deviation was small after sham manoeuvre but increased throughout the experiment. Compliance gain after recruitment was higher in the control group (0.1 ml/cm H2O) compared to the lavage group (0.02 ml/cm H2O, p<0.05). We conclude that lung lavage led to alveolar collapse not susceptible to recruitment manoeuvres. On the contrary in healthy lungs recruitment manoeuvres led to persistent lung recruitment which we interpret as recruitment memory.

Assessment of a volume-dependent dynamic respiratory system compliance in ALI/ARDS by pooling breathing cycles.

New methods were developed to calculate the volume-dependent dynamic respiratory system compliance (C(rs)) in mechanically ventilated patients. Due to noise in respiratory signals and different characteristics of the methods, their results can considerably differ. The aim of the study was to establish a practical procedure to validate the estimation of intratidal dynamic C(rs). A total of 28 patients from intensive care units of eight German university hospitals with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) were studied retrospectively. Dynamic volume-dependent C(rs) was determined during ongoing mechanical ventilation with the SLICE method, dynostatic algorithm and adaptive slice method. Conventional two-point compliance C(2P) was calculated for comparison. A number of consecutive breathing cycles were pooled to reduce noise in the respiratory signals. C(rs)-volume curves produced with different methods converged when the number of pooling cycles increased (n ≥ 7). The mean volume-dependent C(rs) of 20 breaths was highly correlated with mean C(2P) (C(2P,mean) = 0.945 × C(rs,mean) - 0.053, r(2) = 0.968, p < 0.0001). The Bland-Altman analysis indicated that C(2P,mean) was lower than C(rs,mean) (-2.4 ± 6.4 ml cm(-1) H(2)O, mean bias ± 2 SD), but not significant according to the paired t-test (p > 0.05). Methods for analyzing dynamic respiratory mechanics are sensitive to noise and will converge to a unique solution when the number of pooled cycles increases. Under steady-state conditions, assessment of the volume-dependent C(rs) in ALI/ARDS patients can be validated by pooling respiratory data of consecutive breaths regardless of which method is applied. Confidence in dynamic C(rs) determination may be increased with the proposed pooling.

Locally measured shear moduli of pulmonary tissue and global lung mechanics in mechanically ventilated rats.

This study was aimed at measuring shear moduli in vivo in mechanically ventilated rats and comparing them to global lung mechanics. Wistar rats (n = 28) were anesthetized, tracheally intubated, and mechanically ventilated in supine position. The animals were randomly assigned to the healthy control or the lung injury group where lung injury was induced by bronchoalveolar lavage. The respiratory system elastance E(rs) was analyzed based on the single compartment resistance/elastance lung model using multiple linear regression analysis. The shear modulus (G) of alveolar parenchyma was studied using a newly developed endoscopic system with adjustable pressure at the tip that was designed to induce local mechanostimulation. The data analysis was then carried out with an inverse finite element method. G was determined at continuous positive airway pressure (CPAP) levels of 15, 17, 20, and 30 mbar. The resulting shear moduli of lungs in healthy animals increased from 3.3 ± 1.4 kPa at 15 mbar CPAP to 5.8 ± 2.4 kPa at 30 mbar CPAP (P = 0.012), whereas G was ~2.5 kPa at all CPAP levels for the lung-injured animals. Regression analysis showed a negative correlation between G and relative E(rs) in the control group (r = -0.73, P = 0.008 at CPAP = 20 mbar) and no significant correlation in the lung injury group. These results suggest that the locally measured G were inversely associated with the elastance of the respiratory system. Rejecting the study hypothesis the researchers concluded that low global respiratory system elastance is related to high local resistance against tissue deformation.