Low-frequency Forced Oscillation Technique Research Articles

Adaptive Excitation Signals for Low-Frequency Forced Oscillation Technique Measurements in Patients

The low-frequency forced oscillation technique (FOT) has a high diagnostic potential for the detection of respiratory diseases. However, it is not yet widely accepted in clinical practice, partly because the natural breathing frequency usually interferes with the measurement, thus requiring patient-unfriendly breathing maneuvers. The presence of a subject’s breathing generally results in patient-unfriendly measurement protocols. These are needed to extract the important low-frequency information about the subject’s respiratory system. This work presents a technique enabling the application of low-frequency FOT during spontaneous breathing. This is accomplished by adding an external visual stimulus to encourage the subject to synchronize his/her breathing to the measurement apparatus, in combination with an excitation signal that is adapted to the subject’s natural breathing frequency. In this way, the contributions of the breathing and the excitation signal can be separated. This article discusses the implementation, testing, and actual measurement results in a clinical setting using this method.

Strain-specific differences in lung tissue viscoelasticity of mechanically ventilated infant Sprague-Dawley and Wistar rats.

Rats are often used in ventilator-induced lung injury (VILI) models. However, strain-specific susceptibility for VILI has not been elucidated yet. The aim of this study was to demonstrate strain-specific differences in VILI in infant Sprague-Dawley and Wistar rats. VILI was compared in 2-wk-old pups after 8 h of protective or injurious ventilation. Pups were ventilated with tidal volumes (VT) of ∼7 mL/kg and positive end-expiratory pressures (PEEP) of 6 cmH2O (VT7 PEEP6) or with VT of ∼21 mL/kg and PEEP 2 cmH2O (VT21 PEEP2). Interleukin-6, macrophage inflammatory protein-2 (MIP-2), inflammatory cells, and albumin in bronchoalveolar lavage fluid (BALF); histology; and low-frequency forced oscillation technique (LFOT) and pressure-volume (PV) maneuvers were assessed. Alveolar macrophages, neutrophils, and MIP-2 derived from BALF revealed more pronounced VILI after VT21 PEEP2 in both strains. LFOT and PV analyses demonstrated rat strain-specific differences both at baseline and particularly in response to VT21 PEEP2 ventilation. Sprague-Dawley rats showed higher airway and tissue resistance and elastance values with no difference in hysteresivity between ventilation strategies. Wister rats challenged by VT21 PEEP2 experienced significantly more energy dissipation when compared with VT7 PEEP6 ventilation. In conclusion, both rat strains are useful for VILI models. The degree of VILI severity depends on ventilation strategy and selected strain. However, fundamental and time-dependent differences in respiratory system mechanics exist and reflect different lung tissue viscoelasticity. Hence, strain-specific characteristics of the respiratory system need to be considered when planning and interpreting VILI studies with infant rats.

Men are from Mars, Women are from Venus. Gender specific changes in pulmonary function in 1 year old rats after neonatal hyperoxia exposure

RationalePreterm birth affects about 11% of pregnancies worldwide. The Institute of Medicine estimated the cost associated with premature birth to be $36 billion in 2016. Lungs in preterm infants are in the critical saccular stage of lung development and susceptible to the oxygen‐induced chronic lung disease known as bronchopulmonary dysplasia (BPD). BPD is characterized by functional abnormalities including decreased saccular/alveolar septation, decreased microvascular cross‐sectional area with or without pulmonary hypertension, airway injury with or without increased airway reactivity, and abnormalities of control of breathing in various combinations. While the initial inflammation improves, chronic inflammation ensues for a long time. We tested how neonatal hyperoxia exposure affects lung function one year after birth. We postulated an increase in lung collagen levels reflected by reduced pulmonary function.Methods6 newborn male and female rats in each group were exposed to Hyperoxia (Hx; 85% O2) or Normoxia (Nx; 21% O2) for 14 days, then aged to 1 year in Nx. At one year, lung function was measured using a FlexiVent (Scireq, Montreal, Canada). Using a single frequency forced oscillation manoeuvre and a low‐frequency forced oscillation technique the lung was tested for compliance and resistance. Total lung collagen was determined by a colorimetric assay using Ehrlich's reagent.ResultsAnalysis of one year old rats showed no difference in weight and body length between the Nx and the Hx group within each gender. The inspiratory capacity (IC) was significantly higher in the Hx exposed male rats compared to the Nx exposed male rats (12.6±0.6 ml vs 14.0±0.9 ml; p=0.02). The difference in IC in female rats was significantly lower in the Hx group compared to the Nx group (11.3±0.4 vs 10.1±0.6 ml; p=0.002). Dynamic compliance was significantly increased in the male Hx group compared to the male Nx group (1.43±0.05 vs 1.61±0.11 ml/cm H2O; p=0.04). In contrast, the female Hx group showed significantly reduced compliance compared to the female Nx group (1.32±0.05 vs 1.15±0.17 ml/cm H2O). In addition, the PV loop area was higher in the male Hx group compared to the male Nx group and no difference was found between the two female groups. Total collagen in lung tissue was not different between the male Hx and Nx groups but was higher in the female Hx compared to the Nx group.ConclusionOne year after neonatal Hx exposure, the male lung shows increased compliance and inspiratory capacity compared to the Nx exposed rats suggesting a trend to emphysema. In contrast, female rats show signs of lung fibrosis reflected by reduced compliance and increased total collagen content. This data suggests that neonatal oxygen exposure initiates alterations in inflammatory and repair pathways that are different between male and female rats.Support or Funding InformationNHLBI: R01 HL115061‐01 (Eldridge)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

High tidal volume ventilation does not exacerbate acid-induced lung injury in infant rats

The impact of mechanical ventilation with high VT-low PEEP in infant rats with preinjured lungs is unknown. After tracheal instillation of saline or acid, two week old rats were ventilated with VT 7mL/kg and PEEP 5cm H2O or VT 21mL/kg and PEEP 1cm H2O for 4h. Airway resistance and the coefficient of tissue elastance, measured via low-frequency forced-oscillation technique, and quasi-static pressure-volume curves deteriorated less with high VT-low PEEP when compared with low VT-high PEEP. IL-6 concentration in bronchoalveolar lavage fluid (BALF) did not differ between all ventilated groups. Moreover, differences in BALF protein concentration and histological lung injury scores were independent of applied ventilation strategies. In contrast to experimental studies with adult rats, short-term mechanical ventilation with high VT-low PEEP is not deleterious when compared to low VT-high PEEP in both healthy and pre-injured infant rat lungs. Our results call for caution when extrapolating data from adult studies and highlight the need for age-specific animal models.

Pulmonary mechanical responses to intestinal ischaemia-reperfusion and endotoxin preconditioning

During intestinal ischaemia-reperfusion, endotoxin can be translocated. Pretreatment with sublethal doses of endotoxin develops tolerance to ischaemia-reperfusion in different organs; however, the tolerance to intestinal ischaemia-reperfusion in the lung has rarely been investigated. Our aim was to study the role of endotoxin pretreatment in the mechanical responses and inflammatory activation induced by intestinal ischaemia-reperfusion in the lung. Wistar rats were preconditioned with a sublethal dose of endotoxin on day -3 or -1. On day 0, anesthetized, paralyzed and mechanically ventilated rats were subjected to a 60-min occlusion of the superior mesenteric artery and a subsequent 240-min reperfusion. The low-frequency forced oscillation technique was employed to characterize the separate mechanical responses of the airways and respiratory tissues. Intestinal ischaemia-reperfusion caused a significant decrease in airway resistance and increases in tissue resistance and elastance, nitric oxide synthase and myeloperoxidase activities. Pretreatment with endotoxin modified both the pulmonary mechanical responses and the inflammatory markers in the lung during intestinal ischaemia-reperfusion. We conclude that endotoxin or the endotoxin-induced processes (and humoral mediators) have significant roles in the pathomechanism of the remote pulmonary effect of intestinal ischaemia-reperfusion.

High Tidal Volume Ventilation Is Not Deleterious in Infant Rats Exposed to Severe Hemorrhage

Both high tidal volume (V(T)) ventilation and hemorrhage induce acute lung injury in adult rodents. It is not known whether injurious ventilation augments lung injury in infant rats exposed to severe hemorrhage. Two-week-old rats were allocated for ventilation with VT 7 mL/kg and positive end-expiratory pressure (PEEP) 5 cm H₂O (low V(T)) or V(T) 21 mL/kg and PEEP 1 (high V(T)) for 4 hours. Additional rats were subjected to volume-controlled hemorrhage and delayed saline resuscitation, followed by low V(T) or high V(T) ventilation for 4 hours. Nonventilated control groups were also included. Airway resistance and the coefficient of tissue elastance were derived from respiratory input impedance measurements using the low-frequency forced oscillation technique. Pressure-volume curves were obtained at baseline and at the end of the study. Interleukin-6, macrophage inflammatory protein-2, and tumor necrosis factor alpha were determined in bronchoalveolar lavage fluid (BALF) and serum. In both healthy and hemorrhage-exposed animals, high V(T) resulted in reduced elastance (better lung compliance) and increased transcutaneous oxygen saturation. Interleukin-6 in BALF was greater in ventilated animals when compared with nonventilated controls, but not different among ventilated groups. No significant differences were found for all other inflammatory mediators, total protein concentration in BALF, and histology. High V(T) ventilation with low PEEP improves respiratory system mechanics without causing additional damage to healthy and hemorrhage-exposed infant rats after 4 hours of ventilation. This study highlights the tolerance to high V(T) ventilation in infant rats and underscores the need for age-specific animal models.

Inspiratory Resistive Breathing Induces Acute Lung Injury

Resistive breathing is associated with large negative intrathoracic pressures. Increased mechanical stress induces high-permeability pulmonary edema and lung inflammation. To determine the effects of resistive breathing on the healthy lung. Anesthetized rats breathed through a two-way nonrebreathing valve. The inspiratory line was connected to a resistance setting peak inspiratory tracheal pressure at 50% of maximum (inspiratory resistive breathing), while 100% oxygen was supplied to prevent hypoxemia. Quietly breathing animals (100% oxygen) served as controls. Lung injury was evaluated after 3 and 6 hours of resistive breathing. After both 3 and 6 hours of resistive breathing, lung permeability was increased, as assessed by (99m)Tc-diethylenetriaminepentaacetic acid scintigraphy and Evans blue dye extravasation. Tissue elasticity, measured on the basis of static pressure-volume curves and by the low-frequency forced oscillation technique, was also increased. After both 3 and 6 hours of resistive breathing, gravimetric measurements revealed the presence of pulmonary edema and analysis of bronchoalveolar lavage showed increased total protein content, whereas the total cell count was elevated only after 6 hours of resistive breathing. Cytokine levels were assessed in bronchoalveolar lavage fluid and lung tissue by ELISA and were increased after 6 hours compared with controls. Western blot analysis showed early activation of Src kinase via phosphorylation (at 30 min), and Erk1/2 and IκBα (nuclear factor-κB inhibitor) were phosphorylated at 3 and 6 hours. Pathology revealed the presence of lung injury after resistive breathing. Resistive breathing induces acute lung injury and inflammation.

Neonatal total liquid ventilation: is low-frequency forced oscillation technique suitable for respiratory mechanics assessment?

This study aimed to implement low-frequency forced oscillation technique (LFFOT) in neonatal total liquid ventilation (TLV) and to provide the first insight into respiratory impedance under this new modality of ventilation. Thirteen newborn lambs, weighing 2.5 + or - 0.4 kg (mean + or - SD), were premedicated, intubated, anesthetized, and then placed under TLV using a specially design liquid ventilator and a perfluorocarbon. The respiratory mechanics measurements protocol was started immediately after TLV initiation. Three blocks of measurements were first performed: one during initial respiratory system adaptation to TLV, followed by two other series during steady-state conditions. Lambs were then divided into two groups before undergoing another three blocks of measurements: the first group received a 10-min intravenous infusion of salbutamol (1.5 microg x kg(-1) x min(-1)) after continuous infusion of methacholine (9 microg x kg(-1) x min(-1)), while the second group of lambs was chest strapped. Respiratory impedance was measured using serial single-frequency tests at frequencies ranging between 0.05 and 2 Hz and then fitted with a constant-phase model. Harmonic test signals of 0.2 Hz were also launched every 10 min throughout the measurement protocol. Airway resistance and inertance were starkly increased in TLV compared with gas ventilation, with a resonant frequency < or = 1.2 Hz. Resistance of 0.2 Hz and reactance were sensitive to bronchoconstriction and dilation, as well as during compliance reduction. We report successful implementation of LFFOT to neonatal TLV and present the first insight into respiratory impedance under this new modality of ventilation. We show that LFFOT is an effective tool to track respiratory mechanics under TLV.

Airway and tissue mechanics in ventilated patients with pneumonia

We applied the low-frequency forced oscillation technique (LFOT) to measure respiratory impedance (Zrs) at various positive end-expiratory pressures (PEEPs) in 14 sedated and intubated patients with pneumonia classified into a mild (Group 1) and a severe group (Group 2) based on lung injury scores. The Zrs spectra were fit with the constant-phase (CP) model including Newtonian resistance (R(N)) and tissue damping (G) and elastance (H), a distributed airway resistance (DR) and a distributed tissue elastance (DH) model. Using the CP model, all parameters revealed a negative PEEP dependence (p<0.001) in Group 2 and H was higher in Group 2 (p=0.014). The variability of H from the DH model was nearly significantly larger in Group 1 (p=0.061). Following bronchodilator inhalation, G significantly decreased (p=0.009). Thus, the CP model provides a robust partitioning of Zrs into tissue properties and R(N), a surrogate for airway resistance, while the distributed models suggest that lung heterogeneity decreases with increasing PEEP.

Lung volume recruitment maneuvers and respiratory system mechanics in mechanically ventilated mice

The study aim was to establish how recruitment maneuvers (RMs) influence lung mechanics and to determine whether RMs produce lung injury. Healthy BALB/c mice were allocated to receive positive end-expiratory pressure (PEEP) at 2 or 6 cmH(2)O and volume- (20 or 40 mL/kg) or pressure-controlled (25 cmH(2)O) RMs every 5 or 75 min for 150 min. The low-frequency forced oscillation technique was used to measure respiratory input impedance. Large RMs resulting in peak airway opening pressures (P(ao))>30 cmH(2)O did not increase inflammatory response or affect transcutaneous oxygen saturation but significantly lowered airway resistance, tissue damping and tissue elastance; the latter changes are likely associated with the bimodal pressure-volume behavior observed in mice. PEEP increase alone and application of RMs producing peak P(ao) below 25 cmH(2)O did not prevent or reverse changes in lung mechanics; whereas frequent application of substantial RMs on top of elevated PEEP levels produced stable lung mechanics without signs of lung injury.

Methacholine and Ovalbumin Challenges Assessed by Forced Oscillations and Synchrotron Lung Imaging

Methacholine (Mch) is routinely used to assess bronchial hyperreactivity; however, little is known about the differences in the lung response pattern between this provocation and that observed with ovalbumin (Ova) after allergic sensitization. To compare (1) the central versus peripheral effects of Mch and Ova within the lung by combining measurements of airway and tissue mechanics with synchrotron radiation (SR) imaging, and (2) to assess the extent to which mechanical and imaging parameters are correlated. We used the low-frequency forced oscillation technique and SR imaging in control (n = 12) and ovalbumin-sensitized (n = 13) rabbits, at baseline, during intravenous Mch infusion (2.5 microg/kg/min, 5.0 microg/kg/min, or 10.0 microg/kg/min), after recovery from Mch, and after intravenous Ova injection (2.0 mg). We compared intravenous Mch challenge with inhaled Mch (125 mg/ml, 90 s) in a separate group of control animals (n = 5). Airway conductance and tissue elastance were measured by low-frequency forced oscillation technique. The central airway cross-sectional area, the ventilated alveolar area, and the heterogeneity of specific ventilation were quantified by SR imaging. Mch infusion induced constriction predominantly in the central airways, whereas Ova provocation affected mainly the peripheral airways, leading to severe ventilation heterogeneities in sensitized animals. Mch inhalation affected both conducting and peripheral airways. The correlations between airway conductance and central airway cross-sectional area (R = 0.71) and between tissue elastance and ventilated alveolar area (R = -0.72) were strong. The pattern of lung response caused by intravenous Mch and Ova are fundamentally different. Although inhaled Mch induces a heterogeneous lung response similar to that observed with intravenous allergen, these similar patterns are due to different mechanisms.

Impact of supplemental oxygen in mechanically ventilated adult and infant mice

The aim of the present study was to determine the short-term effects of hyperoxia on respiratory mechanics in mechanically ventilated infant and adult mice. Eight and two week old BALB/c mice were exposed to inspired oxygen fractions [Formula: see text] of 0.21, 0.3, 0.6, and 1.0, respectively, during 120 min of mechanical ventilation. Respiratory system mechanics and inflammatory responses were measured. Using the low-frequency forced oscillation technique no differences were found in airway resistance between different [Formula: see text] groups when corrected for changes in gas viscosity. Coefficients of lung tissue damping and elastance were not different between groups and showed similar changes over time in both age groups. Inflammatory responses did not differ between groups at either age. Hyperoxia had no impact on respiratory mechanics during mechanical ventilation with low tidal volume and positive end-expiratory pressure. Hence, supplemental oxygen can safely be applied during short-term mechanical ventilation strategies in infant and adult mice.

Changes in the mechanical properties of the respiratory system during the development of interstitial lung edema

BackgroundPulmonary edema induces changes in airway and lung tissues mechanical properties that can be measured by low-frequency forced oscillation technique (FOT). It is preceded by interstitial edema which is characterized by the accumulation of extravascular fluid in the interstitial space of the air-blood barrier. Our aim was to investigate the impact of the early stages of the development of interstitial edema on the mechanical properties of the respiratory system.MethodsWe studied 17 paralysed and mechanically ventilated closed-chest rats (325–375 g). Total input respiratory system impedance (Zrs) was derived from tracheal flow and pressure signals by applying forced oscillations with frequency components from 0.16 to 18.44 Hz distributed in two forcing signals. In 8 animals interstitial lung edema was induced by intravenous infusion of saline solution (0.75 ml/kg/min) for 4 hours; 9 control animals were studied with the same protocol but without infusion. Zrs was measured at the beginning and every 15 min until the end of the experiment.ResultsIn the treated group the lung wet-to-dry weight ratio increased from 4.3 ± 0.72 to 5.23 ± 0.59, with no histological signs of alveolar flooding. Resistance (Rrs) increased in both groups over time, but to a greater extent in the treated group. Reactance (Xrs) did not change in the control group, while it decreased significantly at all frequencies but one in the treated. Significant changes in Rrs and Xrs were observed starting after ~135 min from the beginning of the infusion. By applying a constant phase model to partition airways and tissue mechanical properties, we observed a mild increase in airways resistance in both groups. A greater and significant increase in tissue damping (from 603.5 ± 100.3 to 714.5 ± 81.9 cmH2O/L) and elastance (from 4160.2 ± 462.6 to 5018.2 ± 622.5 cmH2O/L) was found only in the treated group.ConclusionThese results suggest that interstitial edema has a small but significant impact on the mechanical features of lung tissues and that these changes begin at very early stages, before the beginning of accumulation of extravascular fluid into the alveoli.

Ovalbumin‐sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation

Asthma is a chronic inflammatory disease that is characterized clinically by airway hyperresponsiveness (AHR) to bronchoconstricting agents. The physiological response of the asthmatic lung to inhaled allergen is often characterized by two distinct phases: an early-phase response (EPR) within the first hour following exposure that subsides and a late-phase response (LPR) that is more prolonged and may occur several hours later. Mouse models of asthma have become increasingly popular and should be designed to exhibit an EPR, LPR and AHR. To determine whether a common model of asthma is capable of demonstrating an EPR, LPR and AHR. BALB/c mice were sensitized to ovalbumin (OVA) and challenged with one or three OVA aerosols. Changes in lung mechanics in response to allergen inhalation were assessed using a modification of the low-frequency forced oscillation technique (LFOT). In order to assess AHR, changes in lung mechanics in response to aerosolized methacholine were assessed using LFOT. Inflammatory cell infiltration into the lung was measured via bronchoalveolar lavage (BAL). ELISAs were used to measure inflammatory cytokines in the BAL and levels of IgE in the serum. An EPR was only detectable after three OVA aerosols in approximately half of the mice studied. There was no evidence of an LPR despite a clear increase in cellular infiltration 6 h post-allergen challenge. AHR was present after a single OVA aerosol but not after three OVA aerosols. The lack of an LPR, limited EPR and the absence of a link between the LPR and AHR highlight the limitations of this mouse model as a complete model of the lung dysfunction associated with asthma.

Lung function tests in neonates and infants with chronic lung disease: Lung and chest‐wall mechanics

This is the fifth paper in a review series that summarizes available data and critically discusses the potential role of lung function testing in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy (CLDI). This review focuses on respiratory mechanics, including chest-wall and tissue mechanics, obtained in the intensive care setting and in infants during unassisted breathing. Following orientation of the reader to the subject area, we focused comments on areas of enquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically with respect to relevant methods, equipment and study design, limitations and strengths of different techniques, and availability and appropriateness of reference data. Recommendations to guide future investigations in this field are provided. Numerous different methods have been used to assess respiratory mechanics with the aims of describing pulmonary status in preterm infants and assessing the effect of therapeutic interventions such as surfactant treatment, antenatal or postnatal steroids, or bronchodilator treatment. Interpretation of many of these studies is limited because lung volume was not measured simultaneously. In addition, populations are not comparable, and the number of infants studied has generally been small. Nevertheless, results appear to support the pathophysiological concept that immaturity of the lung leads to impaired lung function, which may improve with growth and development, irrespective of the diagnosis of chronic lung disease. To fully understand the impact of immaturity on the developing lung, it is unlikely that a single parameter such as respiratory compliance or resistance will accurately describe underlying changes. Assessment of respiratory mechanics will have to be supplemented by assessment of lung volume and airway function. New methods such as the low-frequency forced oscillation technique, which differentiate the tissue and airway components of respiratory mechanics, are likely to require further development before they can be of clinical significance.

Partitioning of Airway and Parenchymal Mechanics in Unsedated Newborn Infants

The recent trend toward development of noninvasive methods that can accurately evaluate the lung periphery has particular relevance for the predominantly parenchymal nature of neonatal respiratory disease. Concerns regarding the safety of sedating newborn (especially preterm) infants have also stimulated a drive toward measurements obtained during natural sleep. This study aimed to adapt existing methodology for the low-frequency forced oscillation technique to obtain partitioned measurements of airway and parenchymal mechanics during unsedated, quiet sleep in newborn infants without a history of previous respiratory disease. A face mask was positioned over the infant's mouth and nose and a brief (4-5 s) breathing pause was induced by evoking the Hering-Breuer reflex via end-inspiratory occlusion at raised lung volume (airway opening occluded at 2 kPa). Airway opening pressure and flow were measured while a pseudorandom noise (2-14 Hz) was applied to the airway. Acceptable pulmonary impedance data were collected in 11 of the 12 infants studied (34.1-42.6 wk postmenstrual age, 1.9-3.9 kg body weight) on 17 (total of 20) occasions. Airway parameters (resistance and inertance) and respiratory tissue parameters were calculated from the resultant impedance spectra. Tissue resistance and tissue elastance decreased with increasing body length albeit at different rates such that hysteresivity (tissue resistance/tissue elastance) also decreased. There was a trend toward reduction in airway resistance with increasing length. Measurements of lung function are feasible in the unsedated newborn infant using low-frequency forced oscillations and confirm the important contribution of tissue resistance to lung mechanics in the developing lung.

Developmental changes in airway and tissue mechanics in mice

Most studies using mice to model human lung diseases are carried out in adults, although there is emerging interest in the effects of allergen, bacterial, and viral exposure early in life. This study aims to characterize lung function in BALB/c mice from infancy (2 wk) through to adulthood (8 wk). The low-frequency forced oscillation technique was used to obtain impedance data, partitioned into components representing airway resistance, tissue damping, tissue elastance, and hysteresivity (tissue damping/tissue elastance). Measurements were made at end-expiratory pause (transrespiratory system pressure = 2 cmH2O) and during relaxed slow expiration from 20 to 0 cmH2O. Airway resistance decreased with age from 0.63 cmH2O x ml(-1) x s at 2 wk to 0.24 cmH2O x ml(-1) x s at 8 wk (P < 0.001). Both tissue damping and tissue elastance decreased with age (P < 0.001) from 2 to 5 wk, then plateaued through to 8 wk (P < 0.001). This pattern was seen both in measurements taken at end-expiratory pause and during expiration. There were no age-related changes seen in hysteresivity when measured at end-expiratory pause, but the pattern of volume dependence did differ with the age of the mice. These changes in respiratory mechanics parallel the reported structural changes of the murine lung from the postnatal period into adulthood.

Effect of pulmonary edema on changes in lung mechanics in rats.

Because of similar pathophysiologic changes, oleic acid (OA)-induced pulmonary edema has been well established as an experimental model of certain types of ARDS. Data in the literature indicate changes mostly in global pulmonary mechanical parameters (lung resistance and compliance) during permeability-type edema. Therefore, we designed this study (1) to separate the OA-induced mechanical responses into airway and parenchymal components, and (2) to examine the relationship between the mechanical parameters and the degree of edema. Anaesthetized, paralyzed, mechanically ventilated rats were given iv. OA in doses of 0 (C n=9), 0.05 (OA0.05 n=8), 0.1 (OA0.1 n=10) and 0.3 (OA0.3 n=5) ml/kg. Respiratory system impedance was measured with a wave-tube low-frequency forced oscillation technique, and a model fitting was used to estimate airway (Raw) and lung tissue parameters (G, parenchymal damping; H, elastance). Pulmonary edema was quantified by gravimetric analysis (WW/DW, wet-to-dry weight ratio). In the OAL0.05 group, transient, but significant increase in Raw, only slight increase in H, and no response in G was observed. Different responses were obtained in OA0.1: significant Raw, G, and H values in survivors; rapid and significantly higher responses in all three parameters in non-survivors. Extremely large parameter values were measured in OA0.3. We found that OA caused dose-related increases in WW, DW and WW/DW. Highly significant correlations were found between the degree of edema and G or H, but not Raw. This study demonstrates that low dose of OA had only transient lung mechanical effects; however, it resulted in mild edema. The higher dose elicited significant airway and tissue changes (smaller responses in survivors than in non-survivors), and severe edema. The strong correlation between lung tissue parameters and the degree of edema suggests that the OA-induced acute lung injury is manifested primarily in the alterations in parenchymal mechanics.

Variability in preterm lamb lung mechanics after intra-amniotic endotoxin is associated with changes in surfactant pool size and morphometry.

Antenatal exposure to intra-amniotic (i.a.) endotoxin initiates a complex series of events, including an inflammatory cascade, increased surfactant production, and alterations to lung structure. Using the low frequency forced oscillation technique as a sensitive tool for measurement of respiratory impedance, we aimed to determine which factors contributed most to measured changes in lung mechanics. Respiratory impedance data obtained from sedated preterm lambs exposed to either i.a. injection with saline or 20 mg of endotoxin 1, 2, 4, and 15 days before delivery at 125 days gestation were studied, and association with indexes of standard lung morphometry, inflammatory response, and alveolar surfactant-saturated phosphatidylcholine (Sat PC) pool size was demonstrated. Reduction in tissue impedance with increasing interval between exposure and delivery was evident as early as 4 days after i.a. endotoxin injection, coinciding with resolution of inflammatory reaction, increased alveolar surfactant pools, and contribution of alveolar ducts to the parenchymal fraction, and a later decrease in the tissue component of the parenchymal fraction. Decreases in tissue damping (resistance) were more marked than decreases in tissue elastance. Log alveolar Sat PC accounted for most variability in tissue damping (88.9%) and tissue elastance (73.4%), whereas tissue fraction contributed 2 and 6.4%, respectively. The alveolar Sat PC pool size was the sole factor contributing to change in tissue hysteresivity. No changes were observed in airway resistance. Despite the complex cascade of events initiated by antenatal endotoxin exposure, variability in lung tissue mechanics is associated primarily with changes in alveolar Sat PC pool and lung morphology.

Monitoring of lung volume recruitment and derecruitment using oscillatory mechanics during high-frequency oscillatory ventilation in the preterm lamb.

To determine whether the low-frequency forced oscillation technique (LFOT) can track changes in lung mechanics resulting from prophylactic intratracheal surfactant and a volume recruitment-derecruitment maneuver during high-frequency oscillatory ventilation (HFOV) and how this relates to the damping of the tracheal pressure waveform (P(tr)). Interventional laboratory study. Rural animal research facility in Western Australia. Sedated newborn preterm lambs. Two separate studies were performed. Study 1 involved a volume recruitment-derecruitment maneuver during HFOV using stepwise changes (4 cm H(2)O) in mean airway opening pressure (P(ao), n = 5). Study 2 involved instillation of 4 mL/kg fetal lung fluid (n = 5) or exogenous surfactant (n = 8) at birth and subsequent intermittent mandatory ventilation for 40 mins. Arterial blood gases were recorded every 10 mins and ventilation was appropriately adjusted to achieve moderate hypercarbia (Paco(2), 50-60 mm Hg). Lung mechanics were measured using LFOT 10 mins following each adjustment in P(ao) in parallel with measurements of P(tr) and tidal volume (study 1) or after 40 mins (study 2). Both the recruitment-derecruitment maneuver and prophylactic surfactant administration achieved similar improvements (decrease) in tissue impedance (Z(ti)). The coefficient of tissue resistance (G) decreased more than the coefficient of tissue elastance (H), consistent with improved homogeneity of the lung tissue compartment as lung volume was recruited. Minimum Z(ti) coincided with minimum tracheal pressure amplitude (DeltaP(tr)) on the deflation limb of the volume recruitment-derecruitment maneuver during HFOV. There was a linear relationship between DeltaP(tr) and H. In the preterm lamb, the LFOT can successfully detect changes in lung mechanics resulting from volume recruitment maneuvers during both HFOV and ventilation at conventional rates and may provide information on ventilation inhomogeneity. Minimization of Z(ti) is crucial to damping of P(tr) and may limit potential barotrauma to proximal alveolar units during establishment of HFOV.