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Mechanical ventilation (MV) is core intensive care unit (ICU) therapy during the Covid-19 pandemic. Optimising MV care to a specific patient with respiratory failure is difficult due to inter- and intra- patient variability in lung mechanics and condition. The ability to accurately predict patient-specific lung response to a change in MV settings would enable semi -automated care and significantly improve the efficiency of MV monitoring and care. It has particular emphasis when considering MV care required to treat Covid-19 patients, who require longer MV care, where patient-specific care can reduce the time on MV required. This study develops a nonlinear smooth hysteresis loop model (HLM) able to capture the essential lung dynamics in a patient-specific fashion from measured ventilator data, particularly for changes of compliance and infection points of the pressure-volume loop. The automated (no human input) hysteresis loop analysis (HLA) method is applied to identify HLM model parameters, enabling automated digital cloning to create a virtual patient model to accurately predict lung response at a specified positive end expiratory pressure (PEEP) level, as well as in response to the changes of PEEP. The performance of this automated digital cloning approach is assessed using clinical data from 4 patients and 8 recruitment maneuver (RM) arms. Validation results show the HLM-based hysteresis loops identified using HLA match clinical pressure volume loops very well with root-mean-square (RMS) errors less than 2% for all 8 data sets over 4 patients, validating the accuracy of the developed HLM in capturing the essential lung physiology and respiratory behaviours at different patient conditions. More importantly, the patient-specific digital clones at lower PEEP levels accurately predict lung response at higher PEEP levels with predicted peak inspiratory pressure (PIP) errors less than 2% in average. In addition, the resulted additional lung volume Vfrc obtained with PEEP changes are predicted with average absolute difference of 0.025L. The overall results validate the versatility and potential of the developed HLM for delineating changes of nonlinear lung dynamics, and its capability to create a predictive virtual patient with use of HLA for future treatment personalization and optimisation in MV therapy. Copyright (C) 2020 The Authors.

Breathing involves fluid-solid interactions in the lung; however, the lack of experimental data inhibits combining the mechanics of air flow to airway deformation, challenging the understanding of how biomaterial constituents contribute to tissue response. As such, lung mechanics research is increasingly focused on exploring the relationship between structure and function. To address these needs, we characterize mechanical properties of porcine airways using uniaxial tensile experiments, accounting for bronchial orientation- and location- dependency. Structurally-reinforced constitutive models are developed to incorporate the role of collagen and elastin fibers embedded within the extrafibrillar matrix. The strain-energy function combines a matrix description (evaluating six models: compressible NeoHookean, unconstrained Ogden, uncoupled Mooney-Rivlin, incompressible Ogden, incompressible Demiray and incompressible NeoHookean), superimposed with non-linear fibers (evaluating two models: exponential and polynomial). The best constitutive formulation representative of all bronchial regions is determined based on curve-fit results to experimental data, accounting for uniqueness and sensitivity. Glycosaminoglycan and collagen composition, alongside tissue architecture, indicate fiber form to be primarily responsible for observed airway anisotropy and heterogeneous mechanical behavior. To the authors' best knowledge, this study is the first to formulate a structurally-motivated constitutive model, augmented with biochemical analysis and microstructural observations, to investigate the mechanical function of proximal and distal bronchi. Our systematic pulmonary tissue characterization provides a necessary foundation for understanding pulmonary mechanics; furthermore, these results enable clinical translation through simulations of airway obstruction in disease, fluid-structure interaction insights during breathing, and potentially, predictive capabilities for medical interventions. STATEMENT OF SIGNIFICANCE: The advancement of pulmonary research relies on investigating the biomechanical response of the bronchial tree. Experiments demonstrating the non-linear, heterogeneous, and anisotropic material behavior of porcine airways are used to develop a structural constitutive model representative of proximal and distal bronchial behavior. Calibrated material parameters exhibit regional variation in biomaterial properties, initially hypothesized to originate from tissue constituents. Further exploration through biochemical and histological analysis indicates mechanical function is primarily governed by microstructural form. The results of this study can be directly used in finite element and fluid-structure interaction models to enable physiologically relevant and more accurate computational simulations aimed to help diagnose and monitor pulmonary disease.

Patients with respiratory failure due to obstructive lung disease present a challenge to the emergency physician. These patients have physiologic abnormalities that prevent adequate gas exchange and lung mechanics which render them at increased risk of cardiopulmonary decompensation when managed with invasive mechanical ventilation. This article addresses key principles when managing these challenging patients: patient-ventilator synchrony, air trapping and auto-positive end-expiratory pressure, and airway pressures. This article provides a practical workflow for the emergency physician responsible for managing these patients.

International audience; Porous materials are highly relevant in engineering and medical applications due to their enhanced properties and lightweight nature. Current micromechanical models of porous materials can accurately predict the response under the assumptions of small deformations and drained conditions, typically driven by imposed deformations. However, the theoretical framework for the micromechanical modeling of porous material driven by pore pressure in the large-deformation range has been understudied. In this work, we develop a finite-deformation variational framework for pressure-driven foams, i.e., materials where the pore pressure in the cavities produces the deformation. We further consider different kinematical constraints in the formulation of boundary conditions: kinematic uniform displacements, periodic displacements and uniform traction. We apply the proposed model in the numerical simulation of lung porous tissue using a spherical alveolar geometry and an image-based geometry obtained from micro-computed-tomography images of rat lung. Our results show that the stress distributions in the spherical alveolar model are highly dependent on the kinematical constraints. In contrast, the stress distribution in the image-based alveolar model is not affected by the choice of boundary conditions. Further, when comparing the response of pressure-driven versus deformation-driven models, we conclude that hydrostatic stresses experience a marked shift in their distribution, whereas the deviatoric stresses remain unaffected. Our findings of how stresses are affected by the choice of boundary conditions and geometry take particular relevance in the simulation of the lungs, where the pressure-driven and deformation-driven cases are related to mechanical ventilation and spontaneous breathing.

Microcystin-LR (MC-LR) can cause serious injuries upon short- and long-term exposures that can be prevented by LASSBio-596 (LB-596), an anti-inflammatory compound. We aimed to test LB-596 following subchronic exposure to MC-LR. Swiss mice received 10 intraperitoneal injections of distilled water (DW) or MC-LR (20 μg/kg bw) every 2 days. On the 10th injection animals receiving DW were gavaged with DW or 50 mg/kg bw of LB-596 for 1 or 7 days (C1D, C7D, CL1D and CL7D groups), whereas those exposed to MC-LR received either DW or 50 mg/kg of LB-596 for 1 or 7 days (T1D, T7D, TL1D and TL7D groups). Twelve hours after the last gavage we assessed respiratory mechanics, and extracted lung and liver for histology, apoptosis, inflammatory biomarkers and MC-LR content. C1D, C7D, CL1D and CL7D were all similar. Mechanical parameters were significantly higher in T1D and T7D compared to the other groups. LB-596 reversed these changes on day 1 of administration. LB-596 reduced inflammatory mediators in lung and liver on day 1 of treatment. On day 7 apoptosis in liver and lung fell even more. Briefly, 7-day administration completely reversed lung and liver changes.

Mechanical ventilation is a primary therapy for patients with acute respiratory failure. However, poorly selected ventilator settings can cause lung damage due to the heterogeneity of healthy and damaged alveoli. A commonly used lung protective strategy is titrating PEEP (positive end expiratory pressure) to minimum elastance. However, in clinical practice this initial PEEP is rarely changed. As lung disease evolves over time, the optimal PEEP required to maintain recruitment also changes. A predictive elastance model could be used to assess whether or not the current PEEP level should be changed based on whether a nearby PEEP had lower elastance. In this study, a physiologically relevant basis function model is developed and tested across the entirety of 18 recruitment manoeuvres. Accurate prediction of pressure and PIP to 10% across each of these data sets validates the functionality of this model.

Background Spontaneous breathing (SB) effort is common in invasively ventilated patients, as they recover or at low sedation levels. SB effort makes estimation of patient-specific lung mechanics difficult as it introduces unknown inputs. Currently, there is no proven, non-invasive method to quantify SB effort. This study develops non-invasive model-based metrics for SB. Methods Lung mechanics are identified using a proven model to identify time-varying elastance over inspiration using retrospective data from 22 patients on neutrally adjusted ventilatory assist (NAVA) ventilation. Two methods are explored to quantify negative elastance values associated with breathing effort: a zero-crossing and a trapezoidal method. Area under the resulting positive and negative portions of the time-varying elastance curve is used to quantify SB. Results The median [interquartile range (IQR)] of AUC quantification of SB for the zero crossing method was −3.29 [−4.80 to −2.50] cmH2O/l, and −1.90 [−2.36 to −1.66] cmH2O/l for the trapezoidal method. AUC values between the two methods were highly correlated, indicating consistency of both model-based methods to quantify SB. Conclusion Two model-based methods for SB quantification provide consistent metrics for SB. These methods provide computationally simple and cost effective methods to estimate SB effort, which may have clinical value in assessing patient-ventilator synchrony, choice of ventilation mode, or need for weaning.

Acute respiratory distress syndrome (ARDS) is associated with high mortality and it is a major clinical problem. A common therapy for ARDS patients is mechanical ventilation (MV). However, poorly applied MV can be potentially fatal and optimal MV settings are patient specific. Thus, choosing a good positive end expiratory pressure (PEEP)-level compromise is a clinical challenge. Physiological modeling of the lung is one way to support the selection of the optimal settings for mechanical ventilation. This research makes the reasonably well-supported assumption that optimal PEEP is in the region of minimal elastance of the lung-tissue. The first order model of pulmonary mechanics (FOM) was modified in two differing ways in order to determine the patient-specific pressure range that coincides with minimal elastance. The extensions to the FOM (multiplicative elastance correction and additive volume correction parameters) are compared and evaluated. The addition of the correction parameters ultimately improved the consistency of the modeled elastance across PEEP levels for most patients tested. The results for minimal elastance were in very similar ranges for both approaches. Although this consistency offers a partial validation of the robustness of the approaches, discernment of the optimal approach cannot be determined. Further validation across differing patient states and experimental inputs must be undertaken to determine which method is more representative of true patient physiology.

Mechanical ventilation (MV) is the primary way to treat patients with acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU). Positive-end-expiratory-pressure (PEEP) is often applied in MV to maximise gas exchange and prevent further lung damage. However, optimal MV with patient-specific PEEP level is subjective, based on clinician experience, thus increasing the risk variability, and cost of care. In this study, a single compartment lung mechanics model is employed to predict pressure outcomes at higher PEEP levels using data from lower PEEP levels. Particularly, a hysteresis loop analysis (HLA) algorithm is applied to both the dynostatic curve and pressure-volume (PV) loop to identify the lung elastance at lower PEEP levels. Pulmonary resistance can then be calculated with measured airway pressure and identified elastance. Finally, the elastance and resistance at higher PEEP levels are predicted based on model fitting techniques to obtain the pressure with changes of PEEP. The result of pressure fitting and prediction show 95% of the airway pressure curve errors are within 3% across all the 8 data sets, while peak-inspiratory-pressure (PIP) prediction errors are within 1% for all data sets. The overall approach is readily automated, thus providing an initial critical information in determining optimal MV and PEEP settings. Such a model could also be used to validate the prediction accuracy of other more complex models and improve the confidence of their clinical application. Most importantly, the ability to predict PIP and overall pressure trajectories provide a means to safely titrate PEEP to optimal levels without the necessary to build an accurate enough mathematical model which could cost plenty of time and effort.

Real-time pulmonary graphics now enable clinicians to view lung mechanics and patient-ventilator interactions on a breath-to-breath basis. Displays of pressure, volume, and flow waveforms, pressure-volume and flow-volume loops, and trend screens enable clinicians to customize ventilator settings based on the underlying pathophysiology and responses of the individual patient. This article reviews the basic concepts of pulmonary graphics and demonstrates how they contribute to our understanding of respiratory physiology and the management of neonatal respiratory failure.

Mechanical ventilation (MV) is the term for all artificial respiration procedures that use a mechanical apparatus to help or to substitute the respiratory function and that can also improve oxygenation and influence lung mechanics. Mechanical ventilation is not a therapy but a support measure that maintains the patient while an indicated structural lesion or functional disorder is corrected. Noninvasive mechanical ventilation (NIMV) is defined as external ventilatory support administered without the need for endotracheal intubation (ETI). This system has the same goals as invasive mechanical ventilation (IMV): increase or substitute the cyclic exchange of alveolar air volume produced by respiratory movements. Both therapies (NIMV and IMV), when applied to patients with respiratory failure, are aimed at achieving sufficient ventilation to maintain a proper gas exchange for the body's metabolic requirements.

We compared the effects of oleanolic acid (OA) vs. dexamethasone on lung mechanics and histology, inflammation, and apoptosis in lung and distal organs in experimental sepsis. Seventy-eight BALB/c mice were randomly divided into two groups. Sepsis was induced by cecal ligation and puncture, while the control group underwent sham surgery. 1h after surgery, all animals were further randomized to receive saline (SAL), OA and dexamethasone (DEXA) intraperitoneally. Both OA and DEXA improved lung mechanics and histology, which were associated with fewer lung neutrophils and less cell apoptosis in lung, liver, and kidney than SAL. However, only animals in the DEXA group had lower levels of interleukin (IL)-6 and KC (murine analog of IL-8) in bronchoalveolar lavage fluid than SAL animals. Conversely, OA was associated with lower inducible nitric oxide synthase expression and higher superoxide dismutase than DEXA. In the experimental sepsis model employed herein, OA and DEXA reduced lung damage and distal organ apoptosis through distinct anti-inflammatory mechanisms.

Background Tidal volume (VT) must be accurately delivered by anaesthesia ventilators in the volume-controlled ventilation mode in order for lung protective ventilation to be effective. However, the impact of fresh gas flow (FGF) and lung mechanics on delivery of VT by the newest anaesthesia ventilators has not been reported. Methods We measured delivered VT (VTI) from four anaesthesia ventilators (Aisys™, Flow-i™, Primus™, and Zeus™) on a pneumatic test lung set with three combinations of lung compliance (C, ml cm H2O−1) and resistance (R, cm H2O litre−1 s−2): C60R5, C30R5, C60R20. For each CR, three FGF rates (0.5, 3, 10 litre min−1) were investigated at three set VTs (300, 500, 800 ml) and two values of PEEP (0 and 10 cm H2O). The volume error = [(VTI −VTset)/VTset] ×100 was computed in body temperature and pressure-saturated conditions and compared using analysis of variance. Results For each CR and each set VT, the absolute value of the volume error significantly declined from Aisys™ to Flow-i™, Zeus™, and Primus™. For C60R5, these values were 12.5% for Aisys™, 5% for Flow-i™ and Zeus™, and 0% for Primus™. With an increase in FGF, absolute values of the volume error increased only for Aisys™ and Zeus™. However, in C30R5, the volume error was minimal at mid-FGF for Aisys™. The results were similar at PEEP 10 cm H2O. Conclusions Under experimental conditions, the volume error differed significantly between the four new anaesthesia ventilators tested and was influenced by FGF, although this effect may not be clinically relevant.

a b s t r a c t Severe malaria is characterised by cerebral oedema, acute lung injury (ALI) and multiple organ dysfunc- tions, however, the mechanisms of lung and distal organ damage need to be better clarified. Ninety-six C57BL/6 mice were injected intraperitoneally with 5 × 106 Plasmodium berghei ANKA-infected erythro- cytes or saline. At day 1, Plasmodium berghei infected mice presented greater number of areas with alveolar collapse, neutrophil infiltration and interstitial oedema associated with lung mechanics impair- ment, which was more severe at day 1 than day 5. Lung tumour necrosis factor- and chemokine (C-X-C motif) ligand 1 levels were higher at day 5 compared to day 1. Lung damage occurred in parallel with distal organ injury at day 1; nevertheless, lung inflammation and the presence of malarial pigment in distal organs were more evident at day 5. In conclusion, ALI develops prior to the onset of cerebral malaria symptoms. Later during the course of infection, the established systemic inflammatory response increases distal organ damage. © 2012 Elsevier B.V. All rights reserved.

This paper describes a model of pulmonary gas exchange including CO2 and O2 storage and transport in the anatomical dead space, alveoli, capillaries, arterial and mixed venous blood. Model simulations of gas exchange, ventilation and perfusion for an average healthy adult were in general in good agreement with previously reported values. However, the model overestimates the heterogeneity of ventilation/perfusion ratios down the lungs. Results indicate that the model is able to simulate the pulmonary gas exchange in healthy human lungs but that modifications are required to counter the large degree of ventilation/perfusion heterogeneity currently simulated by the model.

We analysed the effects of oleanolic acid (OA) on lung mechanics and histology and its possible mechanisms of action in experimental acute lung injury (ALI). BALB/c mice were randomly divided into Control (saline, ip) and ALI (paraquat, 25mg/kg, ip) groups. At 1h, both groups were treated with saline (SAL, 50μl ip), OA (10mg/kg ip), or dexamethasone (DEXA, 1mg/kg ip). At 24h, lung static elastance, viscoelastic pressure, and alveolar collapse reduced more after OA compared to DEXA administration. Tumour necrosis factor-α, macrophage migration inhibitory factor, interleukin-6, interferon-γ, and transforming growth factor-β mRNA expressions in lung tissue diminished similarly after OA or DEXA. Conversely, only OA avoided reactive oxygen species generation and yielded a significant decrease in nitrite concentration. OA and DEXA restored the reduced glutathione/oxidized glutathione ratio and catalase activity while increasing glutathione peroxidase induced by paraquat. In conclusion, OA improved lung morphofunction by modulating the release of inflammatory mediators and oxidative stress.

Asthma is a disease characterized by airways hyperresponsiveness (AHR), which is traditionally thought to involve the large, central airways. However, there is increasing evidence of the importance of peripheral airway involvement in asthma as well. Our group has developed particular expertise in measuring peripheral lung mechanics in both humans and mice. This presentation will review data on lung mechanics in subjects with asthma obtained by both classical means and uniquely through the wedged bronchoscope, as well as relevant experiments in mice. Our findings reveal that the lung periphery is hyperresponsive to stimuli in asthmatic subjects, with evidence of airway closure. We also show that the overall impedance of the lung is determined by a combination of peripheral airway narrowing and central airway shunting that occurs in both normal and asthmatic subjects. Experiments in mice have revealed the importance of airway closure in contributing to the phenomenon of AHR. Based on the effects of fibrin on lung mechanics, fibrin may contribute to airway closure via inactivation of surfactant. Another mechanism contributing to AHR is the heterogeneity of airway narrowing. We have explored this in humans by combining the forced oscillation technique with computerized tomography imaging of the lung, and demonstrated that heterogeneity is common to both normal and asthmatic subjects. Further experiments are ongoing and planned in both mice and humans to elucidate the role of fibrin, surfactant and heterogeneous airway narrowing and closure in contributing to AHR in asthma.

This paper presents a model of the lung mechanics which simulates the pulmonary alveolar ventilation. The model includes aspects of: the alveolar geometry; pressure due to the chest wall; pressure due to surface tension determined by surfactant activity; pressure due to lung tissue elasticity; and pressure due to the hydrostatic effects of the lung tissue and blood. The cross-sectional area of the lungs in the supine position derived from computed tomography is used to construct a horizontally layered model, which simulates heterogeneous ventilation distribution from the non-dependent to the dependent layers of the lungs. The model is in agreement with experimentally measured hysteresis of the pressure-volume curve of the lungs, static lung compliance, changes in lung depth during breathing and density distributions at total lung capacity (TLC) and residual volume (RV). In the dependent layers of the lungs, alveolar collapse may occur at RV, depending on the assumptions concerning lung tissue elasticity at very low alveolar volumes. The model simulations showed that ventilation increased with depth in the lungs, although not as pronounced as observed experimentally. The model simulates alveolar ventilation including all of the mentioned components of the respiratory system and to be validated against all the above mentioned experimental data.

We hypothesized that bone marrow-derived mononuclear cells (BMDMC) would attenuate the remodeling process in a chronic allergic inflammation model. C57BL/6 mice were assigned to two groups. In OVA, mice were sensitized and repeatedly challenged with ovalbumin. Control mice (C) received saline under the same protocol. C and OVA were further randomized to receive BMDMC (2×106) or saline intravenously 24h before the first challenge. BMDMC therapy reduced eosinophil infiltration, smooth muscle-specific actin expression, subepithelial fibrosis, and myocyte hypertrophy and hyperplasia, thus causing a decrease in airway hyperresponsiveness and lung mechanical parameters. BMDMC from green fluorescent protein (GFP)-transgenic mice transplanted into GFP-negative mice yielded lower engraftment in OVA. BMDMC increased insulin-like growth factor expression, but reduced interleukin-5, transforming growth factor-β, platelet-derived growth factor, and vascular endothelial growth factor mRNA expression. In conclusion, in the present chronic allergic inflammation model, BMDMC therapy was an effective pre-treatment protocol that potentiated airway epithelial cell repair and prevented inflammatory and remodeling processes.

Summary Mechanical ventilation is a fundamental tool in the clinical daily management of anesthetic procedures and it constitutes a cornerstone in the final evolution of the critical patients. Historically, Volume-controlled ventilation (VCV) has been the universal ventilatory mode used by the anesthesiologists in operating theatre. Nevertheless, since Pressure-controlled ventilation (PCV) was proposed as an alternative to VCV in ICU patients with ALI/ARDS, there has been renewed interest in ventilatory pressure modes in anesthesia. At present the anesthesia workstations usually have available some different modes such as PCV or pressure support ventilation (PSV). The purpose of this review is to evaluate whether ventilatory pressure modes, such as the PCV offer some benefit over the classic VCV, during anesthesia for different types of patients and surgery.

The incidence of asthma is increasing worldwide, but morbidity and mortality are decreasing because of improvements in medical care. Although the incidence of severe perioperative bronchospasm is relatively low in asthmatics undergoing anaesthesia, when it does occur it may be life-threatening. The keys to an uncomplicated perioperative course are assiduous attention to detail in preoperative assessment, and maintenance of the anti-inflammatory and bronchodilatory regimens through the perioperative period. Potential trigger agents should be identified and avoided. Many routinely used anaesthetic agents have an ameliorative effect on airway constriction. Nonetheless, acute bronchospasm can still occur, especially at induction and emergence, and should be promptly and methodically managed.

This study investigated the impact of three different oral nutritional support regimens on lung mechanics and remodelling in young undernourished Wistar rats. In the nutritionally deprived group, rats received one-third of their usual daily food consumption for 4 weeks. Undernourished rats were divided into three groups receiving a balanced, glutamine-supplemented, or long-chain triglyceride-supplemented diet for 4 weeks. In the two control groups, rats received food ad libitum for 4 (C4) or 8 weeks. Lung viscoelastic pressure and static elastance were higher in undernourished compared to C4 rats. After refeeding, lung mechanical data remained altered except for the glutamine-supplemented group. Undernutrition led to a reduced amount of elastic and collagen fibres in the alveolar septa. Elastic fibre content returned to control with balanced and glutamine-supplemented diets, but increased with long-chain triglyceride-supplemented diet. The amount of collagen fibre augmented independent of nutritional support. In conclusion, glutamine-supplemented diet is better at reducing morphofunctional changes than other diets after 4 weeks of refeeding.

In heart failure lung dysfunction is frequent and is greater the greater the heart failure severity. It can be evaluated in terms of lung mechanics and gas diffusion. Indeed heart-lung interaction is related to heart dimensions and lung fluid content; furthermore heart-lung interaction is influenced by the body position. Lung diffusion is also altered in patients with chronic heart failure, and a low gas diffusion is associated with a reduced performance. During exercise, heart-lung interaction becomes more evident. Heart failure patients show an abnormal hyperventilation due to a progressively increased respiratory rate, and a lower tidal volume; hyperventilation is due to different causes including enhanced responses from chemo- and metabolo-receptors, increased CO(2) production and increased dead space ventilation. Several drugs affect the ventilatory pattern in heart failure patients: ACE-inhibitors and anti-aldosteronic drugs improve lung diffusion and ventilatory efficiency during exercise; beta-blockers reduce exercise-induced hyperventilation. Furthermore, ultrafiltration improves lung mechanics, both at rest and during exercise, through body fluid content reduction.

Lung function and bronchoalveolar lavage (BAL) fluid are commonly analyzed to assess the severity of lung disease in sacrificed animals. The input impedance of the respiratory system (Z(rs)) was measured and BAL fluid was collected in intubated, anesthetized, mechanically ventilated rats on three occasions 1 week apart. Measurements were performed in control animals (group C), while lung injury was induced in the other group (group LPS) by i.p. injection of lipopolysaccharide (LPS) before the second measurement. The airway resistance (R(aw)), tissue damping (G) and elastance (H) were determined from the Z(rs) spectra. The total cell counts (TC) from 0.3- to 0.4-ml BAL fluid were also determined. R(aw) exhibited no significant change in either group C (-6.7+/-3.6[S.E.]%) or LPS (-0.9+/-3.7%). Reproducible G and H values were obtained in group C (2.5+/-5.3%, -7.0+/-4.4%), while G and H increased in group LPS (18.4+/-6.5%, 14.9+/-13.8%, p0.05). The changes in TC followed a similar pattern to those observed in G, with no change in group C (-7.9+/-30%), but with a marked increase in group LPS (580+/-456%, p0.05). The method devised for repeated BAL measurements in another group of rats without intubation and muscle relaxant resulted in similar results in BAL profile. We conclude that longitudinal follow-up of the airway and tissue mechanics and inflammatory cells in the BAL fluid are feasible in rats. The current method allows an early detection of lung injury, even in a relatively mild form.

Advances in computed tomographic (CT) imaging of the lung in the past decade, particularly with increased speed, resolution, gating capability, and rapidly expanding volumetric image acquisition, along with advances in image processing, have expanded the repertoire of imaging methods beyond anatomic visualization into the noninvasive study of regional lung physiological function. Recognizing that significant local disease or dysfunction can exist before global measures begin to deteriorate, the motivation for the development and application of these regional techniques is to further our understanding of the basic pathophysiological characteristics of evolving lung disease and, ultimately, develop sensitive measures for its early detection. This review emphasizes the key elements of ventilation and lung mechanics relevant for regional approaches and CT measurement principles available for their study. Examples of established and evolving methods for imaging regional ventilation and mechanics, including the xenon CT ventilation method; the relationship between changing regional CT density and air volume change; and registration-based methods for examining regional lung expansion and strain, are presented.

This review summarizes current clinical use of the forced oscillation technique (FOT) for analysis of lung function. It presents an intuitive approach to FOT pattern recognition for interpretation of results in human subjects, and the view that FOT is now well established and, clinically, eminently useful in patients with airflow obstruction. The focus of this review is on findings that relate directly to clinical utility, with less emphasis on theoretical mechanisms. The major thrust for clinical application of FOT derives from a number of European clinical research centers. Farre and Navajas and their colleagues in Barcelona, Harf and the Lorinos and their coworkers in Paris, Peslin and Duvivier and their coworkers in Vandoeuvre-les-Nancy, Pride and coworkers in London, and Van de Woestijne, Clement, Demedts, Landser, Van Noord, and their colleagues in Leuven have essentially been responsible for clinical development of FOT over the past 25 years. Publishing space does not permit an exhaustive listing of the many contributions of these investigators, but it is intended that the present review will provide a useful infrastructure from which the reader may progress to other research citations as desired.

After hyperinflation to produce maximal dynamic lung compliance (Cdyn), the effects of artificial ventilation at constant frequency (f) and tidal volume (VT) for over a 2-hour period on rapidly adapting pulmonary stretch receptor (RAR) activity and lung mechanics were investigated in anesthetized rabbits. At a 20 min from maximal Cdyn the RARs began to significantly increase their activity, and this increase coincided with the increase in tracheal pressure (PT). Afterward, the increases in RAR activity and PT developed more slowly. Throughout the sustained constant artificial ventilation, the values of VT and respiratory airflow were not significantly different from controls. At 2 hours after maximal Cdyn, atropine (2 mg/kg) did not significantly alter either the increases in RAR activity and total lung resistance (RL) or the decrease in Cdyn, but hyperinflation reverted those responses to the control levels. These results suggest that the sustained artificial ventilation increases lung stiffness to invariably stimulate RARs, but that the response is not involved in vagally mediated bronchoconstriction.

In eight anesthetized, spontaneously breathing New Zealand rabbits airflow, tidal volume, tracheal and esophageal pressures were measured. Frequency, inspiratory and expiratory durations, respiratory system and lung resistances, and elastances, total postinspiratory muscle pressure and its timing parameters were determined. The measurements were performed: (a) under control condition; (b) continuously, during the first 90 sec of the inhalation of a mixture of 5% CO2 + 95% O2, (carbogen, CI); and (c) 6 min after the start of CI. During CI both lung resistance and elastance decreased, and inspiratory driving pressure and postinspiratory muscle pressure increased. No modification could be detected in either the pattern or the duration of postinspiratory muscle activity. In conclusion, mechanical changes precede and facilitate the ventilatory adjustment to CO2 in rabbits.

Emphasis is on the mechanical properties of the spontaneously breathing patient. The occasional reference to mechanically ventilated patients is used to clarify and provide additional insight to the topic of spontaneously breathing individuals. Reference to the basic principles of mechanics are to establish the foundation for an integrated description of lung mechanics. Finally, a brief review of the "state of the art" respiratory monitoring parameters shown to have direct clinical applications.

Since the earliest description of the adult respiratory distress syndrome (ARDS), impaired lung compliance has been a key diagnostic feature. Newer data suggest that a clear understanding of the mechanisms of acute lung injury may be needed to select the ventilatory pressures and patterns of flow delivery required for optimal gas exchange, adequate oxygen supply to tissue, and avoidance of barotrauma. This discussion briefly reviews the ARDS-specific derangements of lung mechanisms, describes measurement techniques applicable to the clinical setting, and suggests ways in which such information can be used in patient management.

Surfactant spreading phenomena on thin films is a fundamental problem in a number of fields including biomedical and chemical engineering. Coating processes, film drainage, and paint technology are all examples of technological applications. Research in this area has experienced a recent surge of activity, partly due to the biomedical applications of surfactant replacement therapy in prematurely born infants. A brief review of the surfactant spreading literature is given in this letter.

Standardized intra-abdominal hemorrhage was induced in 7 anesthetized pigs. The resulting hypovolemic shock was treated with pneumatic anti-shock garment (PASG) followed by intra-aortic balloon occlusion. The effects of this treatment on circulation, lung mechanics and gas exchange were studied. Hemorrhage was induced by pulling out sutures introduced in the inferior caval vein. We found that the use of PASG partially restored mean arterial blood pressure from 44 +/- 6 to 66 +/- 6 mm Hg. When intraaortic balloon occlusion was added, the arterial pressure returned to basal levels. Cardiac output fell severely due to the hemorrhage from 3.7 +/- 0.2 to 1.3 +/- 0.2 liters/min and could not be restored during the treatment. A severe fall in total lung compliance was recorded after inflation of the PASG from 18.6 +/- 0.9 to 10 +/- 0.7 ml/cm H2O, this was accompanied by a fall in alveolar ventilation. These findings emphasize the severe restriction in lung function that occurred during treatment with PASG. Both parameters returned to near normal values when the PASG was deflated and the intra-aortic balloon was inflated. Pulmonary vascular resistance increased by more than 400% and remained high during the study period. There was no change in arterial PO2, however the fall in mixed venous PO2 caused by hemorrhage was reversed at the end of the treatment. Indirect monitoring of cerebral function by continuous EEG showed a decreased voltage during the hemorrhage, this was reversed by the combined treatment. We conclude that the outlined treatment makes it possible to restore central hemodynamics and preserve cerebral function at least for a short period of time until definite surgical treatment can be performed. However, severe restriction on lung mechanics, especially when PASG was inflated, makes it probable that ventilatory support can be necessary in such cases.