Respiratory Tissue Mechanics Research Articles

Benefits of intratracheal and extrathoracic high-frequency percussive ventilation in a model of capnoperitoneum.

Abdominal inflation with CO2 is used to facilitate laparoscopic surgeries, however, providing adequate mechanical ventilation in this scenario is of major importance during anesthesia management. We characterized high-frequency percussive ventilation (HFPV) in protecting from the gas exchange and respiratory mechanical impairments during capnoperitoneum. In addition, we aimed to assess the difference between conventional pressure-controlled mechanical ventilation (CMV) and HFPV modalities generating the high-frequency signal intratracheally (HFPVi) or extrathoracally (HFPVe). Anesthetized rabbits (n = 16) were mechanically ventilated by random sequences of CMV, HFPVi, and HFPVe. The ventilator superimposed the conventional waveform with two high-frequency signals (5 Hz and 10 Hz) during intratracheal HFPV (HFPVi) and HFPV with extrathoracic application of oscillatory signals through a sealed chest cuirass (HFPVe). Lung oxygenation index ([Formula: see text]/[Formula: see text]), arterial partial pressure of carbon dioxide ([Formula: see text]), intrapulmonary shunt (Qs/Qt), and respiratory mechanics were assessed before abdominal inflation, during capnoperitoneum, and after abdominal deflation. Compared with CMV, HFPVi with additional 5-Hz oscillations during capnoperitoneum resulted in higher [Formula: see text]/[Formula: see text], lower [Formula: see text], and decreased Qs/Qt. These improvements were smaller but remained significant during HFPVi with 10 Hz and HFPVe with either 5 or 10 Hz. The ventilation modes did not protect against capnoperitoneum-induced deteriorations in respiratory tissue mechanics. These findings suggest that high-frequency oscillations combined with conventional pressure-controlled ventilation improved lung oxygenation and CO2 removal in a model of capnoperitoneum. Compared with extrathoracic pressure oscillations, intratracheal generation of oscillatory pressure bursts appeared more effective. These findings may contribute to the optimization of mechanical ventilation during laparoscopic surgery.NEW & NOTEWORTHY The present study examines an alternative and innovative mechanical ventilation modality in improving oxygen delivery, CO2 clearance, and respiratory mechanical abnormalities in a clinically relevant experimental model of capnoperitoneum. Our data reveal that high-frequency oscillations combined with conventional ventilation improve gas exchange, with intratracheal oscillations being more effective than extrathoracic oscillations in this clinically relevant translational model.

Changes in lung mechanics and ventilation-perfusion match: comparison of pulmonary air- and thromboembolism in rats

BackgroundPulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism.MethodsAnesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO2 concentration (ETCO2), shape factors, and dead space parameters by volumetric capnography.ResultsIn the presence of a uniform decrease in ETCO2 in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO2, and PaCO2, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting.ConclusionsOur findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO2 elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.

Exaggerated Ventilator-Induced Lung Injury in an Animal Model of Type 2 Diabetes Mellitus: A Randomized Experimental Study.

Although ventilator-induced lung injury (VILI) often develops after prolonged mechanical ventilation in normal lungs, pulmonary disorders may aggravate the development of adverse symptoms. VILI exaggeration can be anticipated in type 2 diabetes mellitus (T2DM) due to its adverse pulmonary consequences. Therefore, we determined whether T2DM modulates VILI and evaluated how T2DM therapy affects adverse pulmonary changes. Rats were randomly assigned into the untreated T2DM group receiving low-dose streptozotocin with high-fat diet (T2DM, n = 8), T2DM group supplemented with metformin therapy (MET, n = 8), and control group (CTRL, n = 8). In each animal, VILI was induced by mechanical ventilation for 4 h with high tidal volume (23 ml/kg) and low positive end-expiratory pressure (0 cmH2O). Arterial and venous blood samples were analyzed to measure the arterial partial pressure of oxygen (PaO2), oxygen saturation (SaO2), and the intrapulmonary shunt fraction (Qs/Qt). Airway and respiratory tissue mechanics were evaluated by forced oscillations. Lung histology samples were analyzed to determine injury level. Significant worsening of VILI, in terms of PaO2, SaO2, and Qs/Qt, was observed in the T2DM group, without differences in the respiratory mechanics. These functional changes were also reflected in lung injury score. The MET group showed no difference compared with the CTRL group. Gas exchange impairment without significant mechanical changes suggests that untreated diabetes exaggerates VILI by augmenting the damage of the alveolar–capillary barrier. Controlled hyperglycemia with metformin may reduce the manifestations of respiratory defects during prolonged mechanical ventilation.

Physiologically variable ventilation in a rabbit model of asthma exacerbation

BackgroundMechanical ventilation during status asthmaticus is challenging and increases the risk of severe complications. We recently reported the value of physiologically variable ventilation (PVV) in healthy and acutely injured lungs. We investigated whether PVV provides benefits compared with pressure-controlled ventilation (PCV) in an experimental model of severe acute asthma. MethodsAllergen-sensitised rabbits were anaesthetised and randomised to either PCV (n=10) or PVV (n=12) during sustained bronchoconstriction induced by allergen and cholinergic stimuli for 6 h. The PVV pattern was generated from pre-recorded spontaneous breathing. Ventilation parameters, oxygenation index (PaO2/FiO2), and respiratory mechanics were measured hourly. Histological injury and inflammation were quantified after 6 h of ventilation. ResultsPVV resulted in lower driving pressures (13.7 cm H2O [12.5–14.9], mean [95% confidence interval]), compared with pressure-controlled ventilation (17.6 cm H2O [15.4–19.8]; P=0.002). PVV improved PaO2/FiO2 (PVV: 55.1 kPa [52–58.2]; PCV: 45.6 kPa [39.3–51.9]; P=0.018) and maintained tissue elastance (PVV: +8.7% [–0.6 to 18]; PCV: –11.2% [–17.3 to –5.1]; P=0.03). PVV resulted in less lung injury as assessed by lower histological injury score (PVV: 0.65 [0.62–0.65]; PCV: 0.71 [0.69–0.73]; P=0.003), cell count (PVV: 247 104 ml−1 [189–305]; PCV: 447 104 ml−1 [324–570]; P=0.005), and protein concentration in bronchoalveolar lavage fluid (PVV: 0.14 μg ml−1 [0.10–0.18]; PCV: 0.21 μg ml−1 [0.15–0.27]; P=0.035). ConclusionsApplying physiological variable ventilation in a model of asthma exacerbation led to improvements in gas exchange, ventilatory pressures, and respiratory tissue mechanics, and reduced lung injury. A global reduction in lung shear stress and recruitment effects may explain the benefits of PVV in status asthmaticus.

Lung volume dependence of respiratory function in rodent models of diabetes mellitus

BackgroundDiabetes mellitus causes the deterioration of smooth muscle cells and interstitial matrix proteins, including collagen. Collagen and smooth muscle cells are abundant in the lungs, but the effect of diabetes on airway function and viscoelastic respiratory tissue mechanics has not been characterized. This study investigated the impact of diabetes on respiratory function, bronchial responsiveness, and gas exchange parameters.MethodsRats were allocated randomly to three groups: a model of type 1 diabetes that received a high dose of streptozotocin (DM1, n = 13); a model of type 2 diabetes that received a low dose of streptozotocin with a high-fat diet (DM2, n = 14); and a control group with no treatment (C, n = 14). Forced oscillations were applied to assess airway resistance (Raw), respiratory tissue damping (G), and elastance (H). The arterial partial pressure of oxygen to the inspired oxygen fraction (PaO2/FiO2) and intrapulmonary shunt fraction (Qs/Qt) were determined from blood gas samples at positive end-expiratory pressures (PEEPs) of 0, 3, and 6 cmH2O. Lung responsiveness to methacholine was also assessed. Collagen fibers in lung tissue were quantified by histology.ResultsThe rats in groups DM1 and DM2 exhibited elevated Raw, G, H, and Qs/Qt, compromised PaO2/FiO2, and diminished airway responsiveness. The severity of adverse tissue mechanical change correlated with excessive lung collagen expression. Increased PEEP normalized the respiratory mechanics, but the gas exchange abnormalities remained.ConclusionsThese findings indicate that diabetes reduces airway and lung tissue viscoelasticity, resulting in alveolar collapsibility that can be compensated by increasing PEEP. Diabetes also induces persistent alveolo-capillary dysfunction and abnormal adaptation ability of the airways to exogenous constrictor stimuli.

Feasibility of forced oscillatory assessment of respiratory mechanics across a laryngeal mask airway in rabbits

Objectives: The forced oscillation technique (FOT) is the method of choice for assessment of respiratory tissue mechanics. A laryngeal mask airway (LMA) is increasingly used to secure the airways in subjects under sedation or general anesthesia. While FOT is routinely performed using an endotracheal tube (ETT), the accuracy of information about airway and tissue mechanics obtained with FOT using a LMA has not been characterized. Therefore, we compared the mechanical parameters obtained with FOT using LMA and ETT in rabbits. Approach: FOT was performed through a LMA at normal and reduced oscillatory amplitudes in anesthetized and mechanically ventilated rabbits (n = 9) at positive end-expiratory pressures (PEEP) of 3 and 6 cmH2O. These measurements were repeated at normal amplitude for the same animal using an ETT. Airway resistance, inertance, respiratory tissue damping (G) and elastance (H) were measured under each condition by FOT. The potential bias of the distensible upper airways when FOT was applied using LMA was assessed with a simulation study. Main results: Values of parameters reflecting airway mechanics were significantly higher when measured using LMA at both PEEPs and oscillatory amplitudes than with ETT. Conversely, regardless of the condition, there was a correlation (r = 0.89 both at normal and reduced amplitudes; p < 0.0001) with good agreement (mean bias of 8.8 cmH2O/l and 11.3 cmH2O/l) in H, whereas G was systematically lower when obtained with LMA than with ETT at PEEP 3 (21.1% ± 7.2% and 9.6% ± 6.9% at normal and reduced oscillatory amplitudes, respectively) and 6 cmH2O (15.1% ± 8.2%, 1.6% ± 9.4%, p < 0.05 for all). Significance: Mechanical properties of the airways and the respiratory tissues, particularly for respiratory tissue stiffness, can be reliably assessed using LMA. However, the involvement of a longer laryngo-tracheo-bronchial pathway when using LMA should be considered for airway resistance and inertance, whereas upper airway shunting may affect the assessment of respiratory tissue damping.

Surgical Repair of Mitral Valve Disease in Children: Perioperative Changes in Respiratory Function.

To assess the profile of changes in airway and respiratory tissue mechanics within a follow-up study performed in children with mitral valve disease, before and after surgical valve repair. Perioperative measurements in a prospective, consecutive cross-sectional study. University hospital, tertiary care teaching hospital The study comprised 24 children with congenital or post-rheumatic mitral valve insufficiency. Input impedance of the respiratory system during spontaneous breathing was measured before and 5 days and 3 weeks after mitral valve surgery. In addition, airway and respiratory tissue mechanics and pulmonary arterial pressure were assessed with the patient under general anesthesia preoperatively and immediately postoperatively. Respiratory tissue elastance and changes in airway measurements were estimated from forced oscillatory impedance data by fitting an appropriate model. Relating airway and respiratory tissue mechanics to previously established reference values obtained in age-matched healthy control patients revealed abnormal respiratory function (135±6.2% and 148±13% in respiratory elastance and resistance, respectively; p<0.001). Improvement in the airway properties was observed immediately after surgery (-15.2±3.4%; p<0.005) and lasted for the study period (-19±4.1%; p<0.001). Respiratory tissue elastance, which correlated preoperatively to the diastolic pulmonary arterial pressure, decreased only 5 days postoperatively (-20.6±4.1%; p<0.005). However, there was no evidence of a clear, immediate effect of surgery on the tissue mechanical parameters measured intraoperatively despite a decrease in diastolic pulmonary pressure. Mitral valve disease in children leads to abnormal airway and respiratory tissue mechanics. Even though surgical repair of mitral insufficiency alleviates abnormal airway function, residual lung tissue stiffening may persist even weeks after the surgery, contributing to a sustained impairment in lung function.

Exposure to urban PM1 in rats: development of bronchial inflammation and airway hyperresponsiveness.

BackgroundSeveral epidemiological and laboratory studies have evidenced the fact that atmospheric particulate matter (PM) increases the risk of respiratory morbidity. It is well known that the smallest fraction of PM (PM1 - particulate matter having a diameter below 1 μm) penetrates the deepest into the airways. The ratio of the different size fractions in PM is highly variable, but in industrial areas PM1 can be significant. Despite these facts, the health effects of PM1 have been poorly investigated and air quality standards are based on PM10 and PM2.5 (PM having diameters below 10 μm and 2.5 μm, respectively) concentrations. Therefore, this study aimed at determining whether exposure to ambient PM1 at a near alert threshold level for PM10 has respiratory consequences in rats.MethodsRats were either exposed for 6 weeks to 100 μg/m3 (alert threshold level for PM10 in Hungary) urban submicron aerosol, or were kept in room air. End-expiratory lung volume, airway resistance (Raw) and respiratory tissue mechanics were measured. Respiratory mechanics were measured under baseline conditions and following intravenous methacholine challenges to characterize the development of airway hyperresponsiveness (AH). Bronchoalveolar lavage fluid (BALF) was analyzed and lung histology was performed.ResultsNo significant differences were detected in lung volume and mechanical parameters at baseline. However, the exposed rats exhibited significantly greater MCh-induced responses in Raw, demonstrating the progression of AH. The associated bronchial inflammation was evidenced by the accumulation of inflammatory cells in BALF and by lung histology.ConclusionsOur findings suggest that exposure to concentrated ambient PM1 (mass concentration at the threshold level for PM10) leads to the development of mild respiratory symptoms in healthy adult rats, which may suggest a need for the reconsideration of threshold limits for airborne PM1.

Prevention of hyperoxia-induced bronchial hyperreactivity by sildenafil and vasoactive intestinal peptide: impact of preserved lung function and structure.

ObjectiveHyperoxia exposure leads to the development of lung injury and bronchial hyperreactivity (BHR) via involvement of nitric oxide (NO) pathway. We aimed at characterizing whether the stimulation of the NO pathway by sildenafil or vasoactive intestinal peptide (VIP) is able to prevent the hyperoxia-induced development of BHR. The respective roles of the preserved lung volume and alveolar architecture, the anti-inflammatory and anti-apoptotic potentials of these treatments in the diminished lung responsiveness were also characterized.Materials and methodsImmature (28-day-old) rats were exposed for 72 hours to room air (Group C), hyperoxia (>95%, Group HC), or hyperoxia with the concomitant administration of vasoactive intestinal peptide (VIP, Group HV) or sildenafil (Group HS). Following exposure, the end-expiratory lung volume (EELV) was assessed plethysmographically. Airway and respiratory tissue mechanics were measured under baseline conditions and following incremental doses of methacholine to assess BHR. Inflammation was assessed by analyzing the bronchoalveolar lavage fluid (BALF), while biochemical and histological analyses were used to characterize the apoptotic and structural changes in the lungs.ResultsThe BHR, the increased EELV, the aberrant alveolarization, and the infiltration of inflammatory cells into the BALF that developed in Group HC were all suppressed significantly by VIP or sildenafil treatment. The number of apoptotic cells increased significantly in Group HC, with no evidence of statistically significant effects on this adverse change in Groups HS and HV.ConclusionsThese findings suggest that stimulating the NO pathway by sildenafil and VIP exert their beneficial effect against hyperoxia-induced BHR via preserving normal EELV, inhibiting airway inflammation and preserving the physiological lung structure, whereas the antiapoptotic potential of these treatments were not apparent in this process.

Acute hemorrhagic shock decreases airway resistance in anesthetized rat

We studied the relation between changes in pulmonary and systemic hemodynamics to those in the airway resistance, respiratory tissue mechanics, and thoracic gas volume (TGV) following acute hemorrhage and blood reinfusion in rats. Forced oscillation technique was used to measure airway resistance (Raw), respiratory tissue damping, and elastance at baseline and after stepwise 1-ml blood withdrawals up to 5 ml total, followed by stepwise reinfusion up to full restoration. Mean systemic (Pam) and pulmonary arterial pressures and suprarenal aortic blood flow were measured at each step. In supplemental animals, plethysmographic TGV, Pam, and respiratory mechanics measurements were performed. Blood volume loss (BVL) led to proportional decreases in Raw (66.5 ± 8.8 vs. 44.8 ± 9.0 cmH(2)O·s·l(-1) with 5 ml, P < 0.001), Pam, and aortic blood flow. In contrast, tissue damping increased significantly (1,070 ± 91 vs. 1,235 ± 105 cmH(2)O/l, P = 0.009 with 5 ml BVL), whereas tissue elastance did not change significantly. TGV significantly increased with acute BVL (3.7 ± 0.2 vs. 4.2 ± 0.2 ml, P = 0.01). Stepwise reinfusions produced opposite changes in the above parameters, with Raw reaching a higher value than baseline (P = 0.001) upon full volume restoration. Both adrenalin (P = 0.015) and noradrenalin levels were elevated (P = 0.010) after 5-ml blood withdrawal. Our data suggest that the decreases in Raw following BVL may be attributed to the following: 1) an increased TGV enhancing airway parenchymal tethering forces; and 2) an increase in circulating catecholamines. The apparent beneficial effect of a reduction in Raw in acute hemorrhagic shock is counteracted by an increase in dead space and the appearance of peripheral mechanical heterogeneities due to de-recruitment of the pulmonary vasculature.

Changes in Airway and Respiratory Tissue Mechanics After Cardiac Surgery

Because of the critical importance of the first postoperative week in the development of respiratory complications after cardiac surgery, the mechanical properties of the respiratory system in this period were followed up systematically. The input impedance of the respiratory system (Zrs) was measured during spontaneous breathing in patients (n=35) undergoing cardiac surgery on the day before surgery to establish the baseline, and for six days thereafter. The airway resistance was inferred from the average of the resistive component of Zrs, while the changes in respiratory elastance were assessed from the imaginary part of Zrs by model fitting. An assessment was made of the impact on the postoperative changes of factors characteristic of the patients (gender, age, smoking, and obesity) or the surgery duration and the need or not for a cardiopulmonary bypass. Airway resistance increased immediately after extubation (peak rise on day 1, evening: 48+/-10%) and subsequently gradually decreased to the initial level, the recovery proving prolonged in obese patients. Postoperative elevation in elastance peaked later (day 2, evening: 83+/-14%), lasted longer, and was affected by both cardiopulmonary bypass (p<0.05) and obesity (p<0.005). These findings demonstrate the need for particular attention in the postoperative management of patients after cardiac surgery in order to reduce the immediate airway symptoms, and to take steps to maintain the lungs open during the critical postoperative days 2 and 3, especially in obese patients and (or) if the surgery involves the use of cardiopulmonary bypass.

Multiscale modeling in computational biomechanics

Biomechanics is broadly defined as the scientific discipline that investigates the effects of forces acting on and within biological structures. The realm of biomechanics includes the circulatory and respiratory systems, tissue mechanics and mechanotransduction, and the musculoskeletal system and motor control. As in many other biological phenomena, many spatial scales are crossed by biomechanics research: intracellular, multicellular, and extracellular matrices; and tissue, organ, and multiorgan systems. It is well established that the effect of forces at higher scales influence behavior at lower scales and that lower-scale properties influence higher-scale response. However, computational methods that incorporate these interactions in biomechanics are relatively rare. In general, computational models that include representation of multiple spatial or temporal scales are loosely defined as multiscale. The fact that multiscale modeling is not well defined lends the term to a variety of scenarios within the computational physiology community. In biomechanics, multiscale modeling may mean establishing a hierarchical link between the spatial and temporal scales, while the output of a larger-scale system is passed through a finely detailed representation at a lower scale (e.g., body-level movement simulations that provide net joint loading for tissue-level stress analysis). In reality, multiscale modeling may require more intricate representation of interactions among scales. A concurrent simulation strategy is inevitable to adequately represent nonlinear associations that have been known for decades [1].

Desflurane but Not Sevoflurane Impairs Airway and Respiratory Tissue Mechanics in Children with Susceptible Airways

Although sevoflurane and desflurane exert bronchoactive effects, their impact on the airway and respiratory tissue mechanics have not been systematically compared in children, especially in those with airway susceptibility (AS). The aim of this study was to assess airway and respiratory tissue mechanics in children with and without AS during sevoflurane and desflurane anesthesia. Respiratory system impedance was measured in healthy control children (group C, n = 20) and in those with AS (group AS, n = 20). Respiratory system impedance was determined during propofol anesthesia and during inhalation of sevoflurane and desflurane 1 minimum alveolar concentration in random order. Airway resistance, tissue damping, and elastance were determined from the respiratory system impedance spectra by model fitting. Children in group AS exhibited significantly higher respiratory impedance parameters compared with those in group C. Sevoflurane slightly decreased airway resistance (-7.0 +/- 1.5% vs. -4.8 +/- 2.4% in groups C and AS, respectively) in both groups. In contrast, desflurane caused elevations in airway resistance and tissue mechanical parameters, with markedly enhanced airway narrowing in children with AS (18.2 +/- 2.8% vs. 53.9 +/- 5%; P < 0.001 for airway resistance in groups C and AS, respectively). Neither the order of drug administration nor the time after the establishment of their steady state concentrations affected these findings. These results emphasized the deleterious effects of desflurane on the airways, particularly in children with susceptible airways in contrast with the consistent beneficial effects of sevoflurane, questioning the use of desflurane in children with AS.

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.

Hyperoxia-induced changes in mouse lung mechanics: forced oscillations vs. barometric plethysmography.

Hyperoxia-induced lung damage was investigated via airway and respiratory tissue mechanics measurements with low-frequency forced oscillations (LFOT) and analysis of spontaneous breathing indexes by barometric whole body plethysmography (WBP). WBP was performed in the unrestrained awake mice kept in room air (n = 12) or in 100% oxygen for 24 (n = 9), 48 (n = 8), or 60 (n = 9) h, and the indexes, including enhanced pause (Penh) and peak inspiratory and expiratory flows, were determined. The mice were then anesthetized, paralyzed, and mechanically ventilated. Airway resistance, respiratory system resistance at breathing frequency, and tissue damping and elastance were identified from the LFOT impedance data by model fitting. The monotonous decrease in airway resistance during hyperoxia correlated best with the increasing peak expiratory flow. Respiratory system resistance and tissue damping and elastance were unchanged up to 48 h of exposure but were markedly elevated at 60 h, with associated decreases in peak inspiratory flow. Penh was increased at 24 h and sharply elevated at 60 h. These results indicate no adverse effect of hyperoxia on the airway mechanics in mice, whereas marked parenchymal damage develops by 60 h. The inconsistent relationships between LFOT parameters and WBP indexes suggest that the changes in the latter reflect alterations in the breathing pattern rather than in the mechanical properties. It is concluded that, in the presence of diffuse lung disease, Penh is inadequate for characterization of the mechanical status of the respiratory system.

Methacholine responsiveness in infants assessed with low frequency forced oscillation and forced expiration techniques

BACKGROUNDThe contribution of the pulmonary tissues to the mechanical behaviour of the respiratory system is well recognised. This study was undertaken to detect airway and lung tissue responses to inhaled...

Airway and respiratory tissue mechanics in normal infants.

Low-frequency respiratory impedance (Zrs) was measured by applying a forcing signal, between 0.5 and 21 Hz at a transrespiratory pressure of 20 cm H(2)O, in a cross-sectional study of 37 normal infants. A model containing an airway resistance (Raw) and inertance (Iaw) and a tissue damping (G) and elastance (H) was fitted to the individual Zrs. Forced expiratory volume in 0.5 second (FEV(0.5)) was determined using the raised volume rapid thoracic compression technique. Multivariate regression analysis was used to analyze the relationships between the lung function parameters and length. Both airway and tissue parameters showed a decreasing quadratic relationship with increasing length. FEV(0.5) showed an increasing cubic relationship with length. A family history of asthma was found to have a negative effect on Raw, H, and FEV(0.5).

Effect of lung water content, manipulated by intratracheal furosemide, surfactant, or a mixture of both, on compliance and viscoelastic tissue forces in lung-lavaged newborn piglets.

To study the impact of lung water content and its reduction by a topically applied diuretic on respiratory and lung tissue mechanics in comparison with surfactant administration in surfactant-deficient newborn piglets with lavage-induced lung injury. Controlled, randomized study. Animal research facility. Newborn piglets. TREATMENT Piglets were surfactant depleted by lung lavage and, after a pretreatment period, randomly treated with intratracheal furosemide, furosemide and surfactant, or with surfactant alone. Dynamic compliance (C(DYN)), static compliance (C(ST)), stress-adaptation pressures (P(DIFF)) and post mortem lung water content were determined. Static compliance in the furosemide-surfactant group was not significantly higher than in the surfactant group. At the end of the study, C(ST) did not differ between the three groups because C(ST) in the furosemide group had increased to values similar to those of the surfactant-containing treatment groups: C(ST) F+S: 0.73 +/- 0.2 mL/cm H2O/kg body weight (BW); C(ST) S: 0.61 +/- 0.11 mL/cm H2O/kg BW; and C(ST) F: 0.60 +/- 0.19 mL/cm H2O/kg BW). Compliance was inversely and P(DIFF) was directly correlated to lung water (LW) content (C(ST) vs. LW: r2 = .59, p = .001; C(DYN) vs. LW: r2 = .49, p = .006; P(DIFF) vs. LW: r2 = .37, p = .059), independent of the type of treatment. Changes in C(ST) and C(DYN) were inversely related to changes in P(DIFF). Intrapulmonary furosemide was more rapidly absorbed when administered to the surfactant-depleted lung alone compared with the mixture with surfactant, and intrapulmonary furosemide had a rapid systemic effect. Although the combination of surfactant with a diuretic failed to increase respiratory compliance to a significantly larger extent than surfactant alone, furosemide at the end of the study increased respiratory compliance to a level similar to surfactant-containing treatments. Lung water content and, to a lesser extent, the absence or presence of surfactant appeared to determine lung mechanics, and its impact on lung mechanics was similar to surfactant administration.