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

Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model

Mesenchymal stromal cells (MSCs) are considered an important therapeutic tool in cancer therapy. They possess intrinsic therapeutic potential and can also be in vitro manipulated and engineered to produce therapeutic molecules that can be delivered to the site of diseases, through their capacity to home pathological tissues. We have recently demonstrated that MSCs, upon in vitro priming with anti-cancer drug, become drug-releasing mesenchymal cells (Dr-MCs) able to strongly inhibit cancer cells growth

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 ~4 cmH2O 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

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&#8315;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 &#8220;pleural window&#8222; using a stereo microscope at a magnification of 15&#215; (resolution of 7.2 &#956;m). We measured the change in diameter of distribution vessels (50&#8315;200 &#956;m) and corner vessels (&lt;50 &#956;m). 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

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

Effect of the First Year of COVID-19 Pandemic on Ophthalmological Practice: A Multi-Centre Italian Study with a Focus on Medico-Legal Aspects

During the COVID-19 era, several restrictions on surgery have been imposed to reduce the infectious risk among patients and staff and further preserve the availability of critical care resources. The aim of the study was to assess their impact on the ophthalmological practice and its medico-legal implications. A retrospective review of electronic medical records of the ophthalmological departments of the University of Cagliari (SGD) and University Magna Gr&aelig;cia of Catanzaro (UMG), from 16 March 2020 to 14 March 2021 (52 weeks), were compared with data from the corresponding period of the previous year. Weekly data on the number and type of diagnoses and procedures performed were collected and analysed in relation to the weekly average of the total number of COVID-19 patients in intensive care units (ICUs) and inpatients in Sardinia and Calabria. Results showed a significant decrease in cataract surgery operations by 47% and 31%, respectively, in the SGD and UMG (p &lt; 0.05) during the second semester of the year; this drop occurred at the same time as the increase in COVID-19 patients in ICU and those hospitalised in both regions. Additionally, anterior segment surgery decreased at the UMG by 30% (p &lt; 0.05). Vitreoretinal surgery decreased by 27% at the SGD, differently increased amount 31.5% at UMG (p &lt; 0.05). The pandemic had a dramatic impact on elective surgery in ophthalmology, quantifying the backlog is the first step in order to understanding the measures to be taken in near future