After-Effects of Thixotropic Maneuvers on Chest Wall and Compartmental Operational Volumes of Healthy Subjects Using Optoelectronic Plethysmography.

The volumes assessed by optoelectronic plethysmography (OEP) and based on a three-compartmental model provide an accurate breath-by-breath index of expiratory and inspiratory (ribcage muscles and diaphragm) muscle length. Thus, after performing thixotropic maneuvers, OEP may also provide evidence regarding the history-dependent properties of these muscles. We studied the after-effects of different thixotropic conditionings on chest wall (CW) and compartmental operational volumes of 28 healthy subjects (25.5 ± 2.2 years, FVC%pred 94.8 ± 5.5, and FEV1 %pred 95.5 ± 8.9) using OEP. Conditionings were composed of inspiratory or expiratory contractions performed from total lung capacity (TLC) or residual volume (RV). The study protocol was composed of three consecutive contractions of the same maneuver, with 60 s of spontaneous breathing in between, and after-effects were studied in the first seven respiratory cycles of each contraction. Cumulative effects were also assessed by comparing the after-effects of each thixotropic maneuver. Inspiratory contractions performed from both TLC and RV acutely increased end-inspiratory (EIV) CW volumes (all p < 0.0001), mainly on both upper and lower ribcage compartments (i.e., non-diaphragmatic inspiratory muscles and diaphragm, respectively); while, expiratory contractions from RV decreased CW volumes (p < 0.0001) by reducing the upper ribcage and abdominal volumes (all p < 0.0001). The response of the thixotropic maneuvers did not present a cumulative effect. In healthy, the use of the three-compartmental model through OEP allows a detailed assessment of the diaphragm, inspiratory and expiratory muscle thixotropy. Furthermore, specific conditioning maneuvers led to thixotropy of the inspiratory ribcage, diaphragm, and expiratory muscles.

Understanding Vasomotion of Lung Microcirculation by In Vivo Imaging.

The balance of lung extravascular water depends upon the control of blood flow in the alveolar distribution vessels that feed downstream two districts placed in parallel, the corner vessels and the alveolar septal network. The occurrence of an edemagenic condition appears critical as an increase in extravascular water endangers the thinness of the air-blood barrier, thus negatively affecting the diffusive capacity of the lung. We exposed anesthetized rabbits to an edemagenic factor (12% hypoxia) for 120 min and followed by in vivo imaging the micro-vascular morphology through a "pleural window" using a stereo microscope at a magnification of 15× (resolution of 7.2 µm). We measured the change in diameter of distribution vessels (50-200 µm) and corner vessels (<50 µm). On average, hypoxia caused a significant decrease in diameter of both smaller distribution vessels (about ~50%) and corner vessels (about ~25%) at 30 min. After 120 min, reperfusion occurred. Regional differences in perivascular interstitial volume were observed and could be correlated with differences in blood flow control. To understand such difference, we modelled imaged alveolar capillary units, obtained by Voronoi method, integrating microvascular pressure parameters with capillary filtration. Results of the analysis suggested that at 120 min, alveolar blood flow was diverted to the corner vessels in larger alveoli, which were found also to undergo a greater filtration indicating greater proneness to develop lung edema.

Computational micro-scale model of control of extravascular water and capillary perfusion in the air blood barrier.

A computational model of a morphologically-based alveolar capillary unit (ACU) in the rabbit is developed to relate lung fluid balance to mechanical forces between capillary surface and interstitium during development of interstitial edema. We hypothesize that positive values of interstitial liquid pressure Pliq impact on capillary transmural pressure and on blood flow. ACU blood flow, capillary recruitment and filtration are computed by modulating vascular and interstitial pressures. Model results are compared with experimental data of Pliq increasing from ~-10 (control) up to ~4cmH2O in two conditions, hypoxia and collagenase injection. For hypoxia exposure, fitting data requires a linear increase in hydraulic conductivity Lp and capillary pressure PC, that fulfils the need of increase in oxygen delivery. For severe fragmentation of capillary endothelial barrier (collagenase injection), fitting requires a rapid increase in both hydraulic and protein permeability, causing ACU de-recruitment, followed by an increase in PC as a late response to restore blood flow. In conclusion, the model allows to describe the lung adaptive response to edemagenic perturbations; the increase in Pliq, related to the low interstitial compliance, provides an efficient control of extravascular water, by limiting microvascular filtration.

The effect of exogenous surfactant on alveolar interdependence.

To investigate the nature of alveolar mechanical interdependence, we purposefully disturbed the equilibrium condition by administering exogenous surfactant in physiological non-surfactant deprived conditions. Changes in alveolar morphology induced by intra-tracheal delivery of CUROSURF were evaluated after opening a pleural window allowing in-vivo microscopic imaging of sub-pleural alveoli in 6 male anesthetized, tracheotomized and mechanically ventilated rabbits. Surfactant instillation increased the surface area of alveoli smaller than 20,000 µm(2) up to ∼ 50% at 15 min after instillation, reflecting a lowering of surface tension due to local surfactant enrichment. Conversely, for alveoli greater than 20,000 µm(2), surface area decreased by ∼ 5%. Opposite changes in alveolar surface are interpreted as reflecting a new inter-alveolar mechanical equilibrium modified by local surfactant distribution and by a decrease in lung distending pressure. We propose that smaller alveoli, representing the majority of alveolar population, might mostly contribute to improve the oxygenation index following surfactant replacement therapy in case of surfactant deficiency.

Alveolar mechanics studied by in vivo microscopy imaging through intact pleural space.

In six male anesthetized, tracheotomized, and mechanically ventilated rabbits we derived indications on alveolar mechanics from in vivo imaging, using a "pleural window" technique (pleural space intact) that allows unrestrained movement of the same subpleural alveoli (N=60) on increasing alveolar pressure from 4 to 8 cmH2O. Absolute compliance (C(abs), ratio of change in alveolar surface area to the change in alveolar pressure) was significantly lower in smaller compared to larger alveoli. Specific compliance, C(sp), obtained by normalizing C(abs) to alveolar surface area, was essentially independent of alveolar size. Both C(abs) and C(sp) were affected by large variability likely reflecting the complex matching between elastic and surface forces. We hypothesize that the relative constancy of C(sp) might contribute to reduce interregional differences in parenchymal and surface forces in the lung tissue by contributing to assure a uniform stretching in a model of mechanically inter-dependent alveoli.

From morphological heterogeneity at alveolar level to the overall mechanical lung behavior: an in vivo microscopic imaging study.

In six male anesthetized, tracheotomized, and mechanically ventilated rabbits, we imaged subpleural alveoli under microscopic view (60×) through a "pleural window" obtained by stripping the endothoracic fascia and leaving the parietal pleura intact. Three different imaging scale levels were identified for the analysis on increasing stepwise local distending pressure (P ld) up to 16.5 cmH2O: alveoli, alveolar cluster, and whole image field. Alveolar profiles were manually traced, clusters of alveoli of similar size were identified through a contiguity-constrained hierarchical agglomerative clustering analysis and alveolar surface density (ASD) was estimated as the percentage of air on the whole image field. Alveolar area distributions were remarkably right-skewed and showed an increase in median value with a large topology-independent heterogeneity on increasing P ld. Modeling of alveolar area distributions on increasing P ld led to hypothesize that absolute alveolar compliance (change in surface area over change in P ld) increases fairly linearly with increasing initial alveolar size, the corollary of this assumption being a constant specific compliance. Clusters were reciprocally interweaved due to their highly variable complex shapes. ASD was found to increase with a small coefficient of variation (CV <25%) with increasing P ld. The CV of lung volume at each transpulmonary pressure was further decreased (about 6%). The results of the study suggest that the considerable heterogeneity of alveolar size and of the corresponding alveolar mechanical behavior are homogenously distributed, resulting in a substantially homogenous mechanical behavior of lung units and whole organ.

Experimental model to evaluate the effect of hydrothorax and lobar resection on lung compliance.

OBJECTIVES: The objective of this study was to evaluate to what extent lung compliance is affected by the individual and combined action of lung resection and hydrothorax in an animal model. METHODS: Anaesthetized and mechanically ventilated rabbits (weight range 2 ÷ 2.2 kg) were randomized in two groups: (i) experimental hydrothorax (from 2 to 8 ml) (n = 5) and (ii) right lower lobe lobectomy (n = 4) and right middle plus lower lobe resection (n = 2). To obtain lung compliance, we measured alveolar, oesophageal pressures and lung volume during slow inflation manoeuvres in control conditions and after hydrothorax or lung resection. Lung compliance was estimated as the change in lung volume divided by the change in transpulmonary pressure. Based on the changes in compliance of the whole lung, we calculated the corresponding changes in compliance of the right lung, which was directly exposed to unilateral hydrothorax and lobectomy. RESULTS: Average total lung compliance in the control was 3.3 ± 0.8 (SD) ml/cmH2O. Eight millilitres of hydrothorax significantly decreased (P < 0.001) lung compliance to 2.7 ± 0.7 ml/cmH2O and increased pleural liquid pressure at the bottom of the cavity from -1 cmH2O up to ∼ 2.5-3 cmH2O. Resection of the right lower lobe significantly decreased (P < 0.001) lung compliance to 1.75 ± 0.3 ml/cmH2O. Resection of the right middle plus lower lobes significantly decreased (P < 0.001) lung compliance to 1.52 ± 0.4 ml/cmH2O. CONCLUSIONS: Following hydrothorax, the decrease in right lung compliance (∼ 45%) was much greater than that expected based on the estimated decrease in right lung volume (20%). We attribute this difference to the fact that hydrothorax causes the lung to be exposed to positive, rather than sub-atmospheric, pressure, causing atelectasis. Following lobectomy, right lung compliance decreased by 62 and 80% for estimated decreases in lung volume of 30 and 60%. This difference could reflect inaccuracy in the estimate of lung volume reduction based on resected weight and/or surgical damage. We conclude that potential detrimental effects of hydrothorax and lobar resection decrease lung compliance and expose the lung to the risk of over-distension when a chest drain is applied.