Browsing by Author "Medina, Tania"
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Item Extracorporeal membrane oxygenation improves survival in a novel 24-hour pig model of severe acute respiratory distress syndrome(e-Century Pub. Corp, 2016) Araos, Joaquín; Alegría, Leyla; García, Patricio; Damiani, Felipe; Tapia, Pablo; Soto, Dagoberto; Salomón, Tatiana; Rodríguez, Felipe; Amthauer, Macarena; Erranz, Benjamín; Castro, Gabriel; Carreño, Pamela; Medina, Tania; Retamal, Jaime; Cruces, Pablo; Bugedo, Guillermo; Bruhn, AlejandroExtracorporeal membrane oxygenation (ECMO) is increasingly being used to treat severe acute respiratory distress syndrome (ARDS). However, there is limited clinical evidence about how to optimize the technique. Experimental research can provide an alternative to fill the actual knowledge gap. The purpose of the present study was to develop and validate an animal model of acute lung injury (ALI) which resembled severe ARDS, and which could be successfully supported with ECMO. Eighteen pigs were randomly allocated into three groups: sham, ALI, and ALI + ECMO. ALI was induced by a double-hit consisting in repeated saline lavage followed by a 2-hour period of injurious ventilation. All animals were followed up to 24 hours while being ventilated with conventional ventilation (tidal volume 10 ml/kg). The lung injury model resulted in severe hypoxemia, increased airway pressures, pulmonary hypertension, and altered alveolar membrane barrier function, as indicated by an increased protein concentration in bronchoalveolar fluid, and increased wet/dry lung weight ratio. Histologic examination revealed severe diffuse alveolar damage, characteristic of ARDS. Veno-venous ECMO was started at the end of lung injury induction with a flow > 60 ml/kg/min resulting in rapid reversal of hypoxemia and pulmonary hypertension. Mortality was 0, 66.6 and 16.6% in the SHAM, ALI and ALI + ECMO groups, respectively (p < 0.05). This is a novel clinically relevant animal model that can be used to optimize the approach to ECMO and foster translational research in extracorporeal lung support.Item Mapping regional strain in anesthetised healthy subjects during spontaneous ventilation(2019) Cruces, Pablo; Erranz, Benjamin; Lillo, Felipe; Sarabia, Mauricio; Iturrieta, Pablo; Morales, Felipe; Blaha, Katherine; Medina, Tania; Diaz, Franco; Hurtado, DanielIntroduction: Breathing produces a phenomenon of cyclic deformation throughout life. Biomechanically, deformation of the lung is measured as strain. Regional strain recently started to be recognised as a tool in the study of lung pathophysiology, but regional lung strain has not been studied in healthy subjects breathing spontaneously without voluntary or pharmacological control of ventilation. Our aim is to generate three-dimensional (3D) regional strain and heterogeneity maps of healthy rat lungs and describe their changes over time. Methods: Micro-CT and image-based biomechanical analysis by finite element approach were carried out in six anaesthetised rats under spontaneous breathing in two different states, at the beginning of the experiment and after 3 hours of observation. 3D regional strain maps were constructed and divided into 10 isovolumetric region-of-interest (ROI) in three directions (apex to base, dorsal to ventral and costal to mediastinal), allowing to regionally analyse the volumetric strain, the strain progression and the strain heterogeneity. To describe in depth these parameters, and systematise their report, we defined regional strain heterogeneity index [1+strain SD ROI(x)]/[1+strain mean ROI(x)] and regional strain progression index [ROI(x)-mean of final strain/ROI(x)-mean of initial strain]. Results: We were able to generate 3D regional strain maps of the lung in subjects without respiratory support, showing significant differences among the three analysed axes. We observed a significantly lower regional volumetric strain in the apex sector compared with the base, with no significant anatomical systematic differences in the other directions. This heterogeneity could not be identified with physiological or standard CT methods. There was no progression of the analysed regional volumetric strain when the two time-points were compared. Discussion: It is possible to map the regional volumetric strain in the lung for healthy subjects during spontaneous breathing. Regional strain heterogeneity and changes over time can be measured using a CT image-based numerical analysis applying a finite element approach. These results support that healthy lung might have significant regional strain and its spatial distribution is highly heterogeneous. This protocol for CT image acquisition and analysis could be a useful tool for helping to understand the mechanobiology of the lung in many diseases.Item Near-apneic ventilation decreases lung injury and fibroproliferation in an ARDS model with ECMO(2019) Araos, Joaquín; Alegría, Leyla; Garcia, Patricio; Cruces, Pablo; Soto, Dagoberto; Erranz, Benjamín; Amthauer, Macarena; Salomon, Tatiana; Medina, Tania; Rodríguez, Felipe; Ayala, Pedro; Borzone, Gisella R.; Meneses, Manuel; Damiani, Felipe; Retamal, Jaime; Cornejo, Rodrigo; Bugedo, Guillermo; Bruhn, AlejandroRationale: There is wide variability in mechanical ventilation settings during ECMO in ARDS patients. Although lung rest is recommended to prevent further injury, there is no evidence to support it. Objectives: To determine whether near-apneic ventilation decreases lung injury in a pig model of ARDS supported with ECMO. Methods: Pigs (26-36kg; n=24) were anesthetized and connected to mechanical ventilation. In 18 animals lung injury was induced by a double-hit consisting in repeated saline lavages followed by 2 hours of injurious ventilation. Then, animals were connected to high-flow veno-venous ECMO, and randomized into 3 groups: Non-protective (PEEP 5 cmH2O, tidal volume 10 ml/kg, respiratory rate 20 bpm); Conventional-protective (PEEP 10 cmH2O, tidal volume 6 ml/kg, respiratory rate 20 bpm); Near-apneic (PEEP 10 cmH2O, driving pressure 10 cmH2O, respiratory rate 5 bpm). Six other pigs were used as Sham. All groups were maintained during the 24-hour study period. Measurements and Main Results: Minute ventilation and mechanical power were lower in the Near-apneic group, but no differences were observed in oxygenation or compliance. Lung histology revealed less injury in the Near-apneic group. Extensive immunohistochemical staining for myofibroblasts and pro-collagen III was observed in the Non-protective group, with the Near-apneic group exhibiting the least alterations. Near- apneic group showed significantly less matrix-metalloproteinase-2 and -9 activity. Histological lung injury and fibroproliferation scores were positively correlated with driving pressure and mechanical power.Item Progression of regional lung strain and heterogeneity in lung injury: assessing the evolution under spontaneous breathing and mechanical ventilation(2020) Hurtado, Daniel E.; Erranz, Benjamín; Lillo, Felipe; Sarabia-Vallejos, Mauricio A.; Iturrieta, Pablo; Morales, Felipe; Blaha, Katherine; Medina, Tania; Diaz, Franco; Cruces, PabloBackground: Protective mechanical ventilation (MV) aims at limiting global lung deformation and has been associated with better clinical outcomes in acute respiratory distress syndrome (ARDS) patients. In ARDS lungs without MV support, the mechanisms and evolution of lung tissue deformation remain understudied. In this work, we quantify the progression and heterogeneity of regional strain in injured lungs under spontaneous breathing and under MV. Methods: Lung injury was induced by lung lavage in murine subjects, followed by 3 h of spontaneous breathing (SB-group) or 3 h of low Vt mechanical ventilation (MV-group). Micro-CT images were acquired in all subjects at the beginning and at the end of the ventilation stage following induction of lung injury. Regional strain, strain progression and strain heterogeneity were computed from image-based biomechanical analysis. Three-dimensional regional strain maps were constructed, from which a region-of-interest (ROI) analysis was performed for the regional strain, the strain progression, and the strain heterogeneity. Results: After 3 h of ventilation, regional strain levels were significantly higher in 43.7% of the ROIs in the SB-group. Significant increase in regional strain was found in 1.2% of the ROIs in the MV-group. Progression of regional strain was found in 100% of the ROIs in the SB-group, whereas the MV-group displayed strain progression in 1.2% of the ROIs. Progression in regional strain heterogeneity was found in 23.4% of the ROIs in the SB-group, while the MV-group resulted in 4.7% of the ROIs showing significant changes. Deformation progression is concurrent with an increase of non-aerated compartment in SB-group (from 13.3% ± 1.6% to 37.5% ± 3.1%), being higher in ventral regions of the lung. Conclusions: Spontaneous breathing in lung injury promotes regional strain and strain heterogeneity progression. In contrast, low Vt MV prevents regional strain and heterogeneity progression in injured lungs.