Mariangela Pellegrini

Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure

Little is known about the small airways dysfunction in acute respiratory distress syndrome (ARDS). By computed tomography (CT) imaging in a porcine experimental model of early ARDS, we aimed at studying the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction (FIO2). Six piglets were mechanically ventilated under anesthesia and muscle relaxation. Four animals underwent saline-washout lung injury, and two served as healthy controls. Beyond the site of assumed airway closure, gas was expected to be trapped in the injured lungs, promoting alveolar collapse. This was tested by ventilation with an FIO2 of 0.25 and 1 in sequence during low and high distending pressures. In the most dependent regions, the gas/tissue ratio of end-expiratory CT, after previous ventilation with FIO2 0.25 low-driving pressure, was significantly higher than after ventilation with FIO2 1; with high-driving pressure, this difference disappeared. Also, significant reduction in poorly aerated tissue and a correlated increase in nonaerated tissue in end-expiratory CT with FIO2 1 low-driving pressure were seen. When high-driving pressure was applied or after previous ventilation with FIO2 0.25 and low-driving pressure, this pattern disappeared. The findings suggest that low distending pressures produce widespread dependent airway closure and with high FIO2, subsequent absorption atelectasis. Low FIO2 prevented alveolar collapse during the study period because of slow absorption of gas behind closed airways.

Regional distribution of lung compliance by image analysis of computed tomograms

Computed tomography (CT) can yield quantitative information about volume distribution in the lung. By combining information provided by CT and respiratory mechanics, this study aims at quantifying regional lung compliance (CL) and its distribution and homogeneity in mechanically ventilated pigs. The animals underwent inspiratory hold maneuvers at 12 lung volumes with simultaneous CT exposure at two end-expiratory pressure levels and before and after acute lung injury (ALI) by oleic acid administration. CL and the sum of positive voxel compliances from CT were linearly correlated; negative compliance areas were found. A remarkably heterogeneous distribution of voxel compliance was found in the injured lungs. As the lung inflation increased, the homogeneity increased in healthy lungs but decreased in injured lungs. Image analysis brought novel findings regarding spatial homogeneity of compliance, which increases in ALI but not in healthy lungs by applying PEEP after a recruitment maneuver.

Zero expiratory pressure and low oxygen concentration promote heterogeneity of regional ventilation and lung densities

It is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation.

Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung

Objectives: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model. Design: Experimental animal study. Setting: International synchrotron radiation laboratory. Subjects: Four anesthetized rabbits, ventilated in pressure controlled mode. Interventions: The lung was consecutively imaged at ~ 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end-expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (F derecruited, F recruited) were computed based on the comparison of the aerated volumes at successive time points. Measurements and Main Results: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of F derecruited and F recruited when mechanical interdependence was included, while its exclusion gave F recruited values of zero at positive end-expiratory pressure greater than or equal to 3 cm H2O. Conclusions: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage.

Effects of superimposed tissue weight on regional compliance of injured lungs

Computed tomography (CT), together with image analysis technologies, enable the construction of regional volume (VREG) and local transpulmonary pressure (PTP,REG) maps of the lung. Purpose of this study is to assess the distribution of VREG vs PTP,REG along the gravitational axis in healthy (HL) and experimental acute lung injury conditions (eALI) at various positive end-expiratory pressures (PEEPs) and inflation volumes. Mechanically ventilated pigs underwent inspiratory hold maneuvers at increasing volumes simultaneously with lung CT scans. eALI was induced via the iv administration of oleic acid. We computed voxel-level VREG vs PTP,REG curves into eleven isogravitational planes by applying polynomial regressions. Via F-test, we determined that VREG vs PTP,REG curves derived from different anatomical planes (p-values<1.4E-3), exposed to different PEEPs (p-values<1.5E-5) or subtending different lung status (p-values<3E-3) were statistically different (except for two cases of adjacent planes). Lung parenchyma exhibits different elastic behaviors based on its position and the density of superimposed tissue which can increase during lung injury.

Atelectasis is inversely proportional to transpulmonary pressure during weaning from ventilator support in a large animal model

In mechanically ventilated, lung injured, patients without spontaneous breathing effort, atelectasis with shunt and desaturation may appear suddenly when ventilator pressures are decreased. It is not known how such a formation of atelectasis is related to transpulmonary pressure (PL) during weaning from mechanical ventilation when the spontaneous breathing effort is increased. If the relation between PL and atelectasis were known, monitoring of PL might help to avoid formation of atelectasis and cyclic collapse during weaning. The main purpose of this study was to determine the relation between PL and atelectasis in an experimental model representing weaning from mechanical ventilation.

Robustness of two different methods of monitoring respiratory system compliance during mechanical ventilation.

Robustness measures the performance of estimation methods when they work under non-ideal conditions. We compared the robustness of artificial neural networks (ANNs) and multilinear fitting (MLF) methods in estimating respiratory system compliance (CRS) during mechanical ventilation (MV). Twenty-four anaesthetized pigs underwent MV. Airway pressure, flow and volume were recorded at fixed intervals after the induction of acute lung injury. After consecutive mechanical breaths, an inspiratory pause (BIP) was applied in order to calculate CRS using the interrupter technique. From the breath preceding the BIP, ANN and MLF had to compute CRS in the presence of two types of perturbations: transient sensor disconnection (TD) and random noise (RN). Performance of the two methods was assessed according to Bland and Altman. The ANN presented a higher bias and scatter than MLF during the application of RN, except when RN was lower than 2% of peak airway pressure. During TD, MLF algorithm showed a higher bias and scatter than ANN. After the application of RN, ANN and MLF maintain a stable performance, although MLF shows better results. ANNs have a more stable performance and yield a more robust estimation of CRS than MLF in conditions of transient sensor disconnection.

ALVEOLAR DEFLATION DYNAMICS BEFORE AND AFTER LUNG INJURY ASSESSED BY SYNCHROTRON RADIATION COMPUTED TOMOGRAPHY

During mechanical ventilation, reduction of expiratory pressure may trigger heterogeneous processes of derecruitment, collapse and overdistension of airspaces. However the relationship of such processes with precise regional location inside the lung has not been fully studied in vivo. Synchrotron Radiation Computed Tomography (SRCT) can provide in vivo regional images of the lung at resolutions higher than conventional CT.

0897. Mechanisms of pulmonary inflation during lung injury assessed by synchrotron radiation computed tomography

The process of lung inflation during mechanical ventilation is characterized by phenomena of alveolar recruitment and distension but regional interaction and temporal sequence are not known for the core areas of the lung. The only information available are referred to subpleural alveoli, studied by microscopy. Relevance of this issue derives from the notion that 1) radiologic studies reveal that air spaces behavior in the core regions of the parenchyma is very complex 2) unsuited patterns of mechanical ventilation (MV) can trigger a Ventilator-Induced Lung Injury (VILI). Synchrotron Radiation Computed Tomography (SRCT) yields tomographic images at resolutions higher than conventional CT.

0438. Effects of positive end-expiratory pressure (PEEP) on the pattern of breathing during neurally adjusted ventilatory assist. A pilot study in a mild ards porcine model

Spontaneous breathing during mechanical ventilation is still controversial. It is well known that incongruous patterns of mechanical ventilation can trigger or exacerbate lung injury. NAVA is a mode of mechanical ventilation that delivers ventilatory assist in proportion to the Electrical activity of the Diaphragm (EDi), which mirrors the performance of the whole respiratory system. However during NAVA, the effects of PEEP on the EDi signal, respiratory rate and breathing heterogeneity are unknown.