Browsing by Author "Erranz, Benjamín"
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Item A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection(2020) Cruces, Pablo; Retamal, Jaime; Hurtado, Daniel E.; Erranz, Benjamín; Iturrieta, Pablo; González, Carlos; Díaz, FrancoDeterioration of lung function during the first week of COVID-19 has been observed when patients remain with insufficient respiratory support. Patient self-inflicted lung injury (P-SILI) is theorized as the responsible, but there is not robust experimental and clinical data to support it. Given the limited understanding of P-SILI, we describe the physiological basis of P-SILI and we show experimental data to comprehend the role of regional strain and heterogeneity in lung injury due to increased work of breathing. In addition, we discuss the current approach to respiratory support for COVID-19 under this point of viewItem Angiotensin-converting enzyme insertion/deletion polymorphism is associated with severe hypoxemia in pediatric ARDS(Springer, 2012) Cruces, Pablo; Puga, Alonso; Erranz, Benjamín; Donoso, Alejandro; Carvajal, Cristobal; Wilhelm, Jan; Repetto, GabrielaPURPOSE: The D allele of the insertion/deletion (I/D) polymorphism of a 287-bp sequence in the angiotensin-converting enzyme (ACE) gene has been associated with an increased activity of this enzyme. Its role in susceptibility to acute respiratory distress syndrome (ARDS) has not been well defined. We hypothesized that ACE I/D genotype in pediatrics is associated with ARDS and plasma levels of angiotensin II. METHODS: Prospective case-control study in patients under 15 years of age from a mixed Chilean population. Sixty patients with ARDS and 60 controls were included. Association between ACE genotype and ARDS was evaluated as the primary outcome; mortality and severe hypoxemia were examined as secondary outcomes. Plasma angiotensin-II concentration was measured by immunoassay at admission. RESULTS: Frequency of ACE I/D genotype was similar in ARDS and control groups (p = 0.18). In the ARDS group, severe hypoxemia was less frequent in D allele carriers (p < 0.05). Plasma angiotensin-II levels were associated with genotype in the ARDS group, but not controls, being higher in D allele carriers (p = 0.016). CONCLUSION: These data do not support the association between ACE I/D genotype and ARDS, although severe hypoxemia was less frequent in D allele carriers. ACE I/D polymorphism modified angiotensin-II levels in pediatric ARDS, but its pathogenic role is not well understood and needs to be addressed in future studies.Item Consecuencias hemodinámicas y respiratorias del síndrome compartimental abdominal en un modelo experimental(2012) Díaz, Franco; Donso, Alejandro; Carvajal, Cristóbal; Salomón, Tatiana; Torres, María Fernanda; Erranz, Benjamín; Cruces, PabloIntroducción: El síndrome compartimental abdominal (SCA) es una entidad grave, de escaso reporte en población pediátrica por una inadecuada alerta y reconocimiento. Puede ser originado por causas médicas y quirúrgicas, presentando una elevada mortalidad. Objetivo: Determinar la magnitud de las consecuencias hemodinámicas y respiratorias iniciales desencadenadas por la inducción de un SCA en un modelo experimental. Método: Doce cerdos anestesiados (4,8 ± 0,1 kg). El SCA fue inducido con instilación de solución coloide en cavidad peritoneal para obtener una presión intra-abdominal (PIA) de 25 ± 5 mmHg. En condiciones basales y posterior a inducción del SCA se realizó monitorización hemodinámica convencional y termodilución transpulmonar. Paralelamente se midió gasometría arterial y análisis de mecánica pulmonar. Resultados: Hubo una reducción del gasto cardíaco en 16% (5,19 ± 0,33 a 4,34 ± 0,28 l/min/m2, p = 0,01) y de la presión de perfusión abdominal en 20% (72,3 ± 3,2 a 57,3 ± 4,0 mmHg, p < 0,001) sin cambios en frecuencia cardiaca, presión arterial y venosa central. Además ocurrió un deterioro de la compliance del sistema respiratorio cercana al 50% (1,28 ± 0,09 a 0,62 ± 0,04 ml/cmH2O/kg, p = 0,002) asociado a un incremento significativo en las presiones intratorácicas y disminución leve de la oxigenación. Discusión: En este modelo experimental se pudo apreciar el desarrollo temprano de disfunción hemodinámica y pulmonar. Se evidenció una reducción de gasto cardiaco no detectado por la monitorización convencional y un deterioro substancial de la mecánica pulmonar, propia de una enfermedad restrictiva, asociado a alteraciones leves del intercambio gaseoso. Creemos que es fundamental monitorizar la PIA en pacientes predispuestos a desarrollar un SCA, más aún ante empeoramiento de disfunciones orgánicas dado que la hipotensión e hipoxemia grave son signos tardíos de esta complicación.Item Decreased lung compliance increases preload dynamic tests in a pediatric acute lung injury model(Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U., 2015) Erranz, Benjamín; Díaz, Franco; Donoso, Alejandro; Salomón, Tatiana; Carvajal, Cristóbal; Torres, María Fernanda; Cruces, PabloBACKGROUND: Preload dynamic tests, pulse pressure variation (PPV) and stroke volume variation (SVV) have emerged as powerful tools to predict response to fluid administration. The influence of factors other than preload in dynamic preload test is currently poorly understood in pediatrics. The aim of our study was to assess the effect of tidal volume (VT) on PPV and SVV in the context of normal and reduced lung compliance in a piglet model. MATERIAL AND METHOD: Twenty large-white piglets (5.2±0.4kg) were anesthetized, paralyzed and monitored with pulse contour analysis. PPV and SVV were recorded during mechanical ventilation with a VT of 6 and 12mL/kg (low and high VT, respectively), both before and after tracheal instillation of polysorbate 20. RESULTS: Before acute lung injury (ALI) induction, modifications of VT did not significantly change PPV and SVV readings. After ALI, PPV and SVV were significantly greater during ventilation with a high VT compared to a low VT (PPV increased from 8.9±1.2 to 12.4±1.1%, and SVV from 8.5±1.0 to 12.7±1.2%, both P<0.01). CONCLUSIONS: This study found that a high VT and reduced lung compliance due to ALI increase preload dynamic tests, with a greater influence of the latter. In subjects with ALI, lung compliance should be considered when interpreting the preload dynamic tests.Item Diferencia veno-arterial de dióxido de carbono como predictor de gasto cardiaco disminuido en modelo pediátrico experimental(Sociedad Medica de Santiago, 2012) Díaz, Franco; Donoso, Alejandro; Carvajal, Cristóbal; Salomón, Tatiana; Torres, María; Erranz, Benjamín; Cruces, PabloBackground: Cardiac output (CO) measurement is not a standard of care for critically ill children, but it can be estimated by indirect methods such as veno-arterial pCO2 difference (ΔVACO2). Aim: To determine the correlation between CO and ΔVACO2 and evaluate the usefulness of ΔVACO2 in the diagnosis of low CO in an experimental pediatric model. Materials and Methods: Thirty piglets weighing 4.8 ± 0.35 kg were anesthetized and monitored with transpulmonary thermodilution. Lung injury was induced with tracheal instillation of Tween 20®. Serial measurements of central venous and arterial blood gases, as well as CO, were obtained at baseline, 1, 2 and 4 h after lung injury induction. Low cardiac output (LCO) was defined as CO lower than 2.5 Llminlm2. Results: There was an inverse correlation between CO and ΔVACO2 (r = -0.36, p < 0.01). ΔVACO2 was 14 ± 8 mmHg in LCO state and 8 ± 6 mmHg when this condition was not present (p < 0.01). Area under the receiver operating characteristic (ROC) curves of ΔVACO2 and LCO state was 0.78 (0.68-0.86). The best cut-point was 8.9 mmHg to determine LCO with a sensibility 0.78, specificity 0.7, positive predictive value 0.27 and negative predictive value 0.96. Conclusions: In this model there was an inverse correlation between ΔVACO2 and CO. The best cutoff value to discard LCO was ΔVACO2 of 8.9 mmHg, indicating that under this value the presence of LCO is very unlikely.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 Implementation of preemptive fluid strategy as a bundle to prevent fluid overload in children with acute respiratory distress syndrome and sepsis(2018) Díaz, Franco; Nuñez, María José; Pino, Pablo; Erranz, Benjamín; Cruces, PabloBackground Fluid overload (FO) is associated with unfavorable outcomes in critically ill children. Clinicians are encouraged to avoid FO; however, strategies to avoid FO are not well-described in pediatrics. Our aim was to implement a bundle strategy to prevent FO in children with sepsis and pARDS and to compare the outcomes with a historical cohort. Methods A quality improvement initiative, known as preemptive fluid strategy (PFS) was implemented to prevent early FO, in a 12-bed general PICU. Infants on mechanical ventilation (MV) fulfilling pARDS and sepsis criteria were prospectively recruited. For comparison, data from a historical cohort from 2015, with the same inclusion and exclusion criteria, was retrospectively reviewed. The PFS bundle consisted of 1. maintenance of intravenous fluids (MIVF) at 50% of requirements; 2. drug volume reduction; 3. dynamic monitoring of preload markers to determine the need for fluid bolus administration; 4. early use of diuretics; and 5. early initiation of enteral feeds. The historical cohort treatment, the standard fluid strategy (SFS), were based on physician preferences. Peak fluid overload (PFO) was the primary outcome. PFO was defined as the highest FO during the first 72 h. FO was calculated as (cumulative fluid input – cumulative output)/kg*100. Fluid input/output were registered every 12 h for 72 h. Results Thirty-seven patients were included in the PFS group (54% male, 6 mo (IQR 2,11)) and 39 with SFS (64%male, 3 mo (IQR1,7)). PFO was lower in PFS (6.31% [IQR4.4–10]) compared to SFS (12% [IQR8.4–15.8]). FO was lower in PFS compared to CFS as early as 12 h after admission [2.4(1.4,3.7) v/s 4.3(1.5,5.5), p < 0.01] and maintained during the study. These differences were due to less fluid input (MIVF and fluid boluses). There were no differences in the renal function test. PRBC requirements were lower during the first 24 h in the PFS (5%) compared to SFS (28%, p < 0.05). MV duration was 81 h (58,98) in PFS and 118 h (85154) in SFS(p < 0.05). PICU LOS in PFS was 5 (4, 7) and in SFS was 8 (6, 10) days. Conclusion Implementation of a bundle to prevent FO in children on MV with pARDS and sepsis resulted in less PFO. We observed a decrease in MV duration and PICU LOS. Future studies are needed to address if PFS might have a positive impact on health outcomes.Item Incorporación de estándares bioéticos para la generación de conocimiento científico de calidad en investigación en fauna silvestre: Ciencia con conciencia(2020) Tadich, Tamara A.; Freslón, Inés de; Gallo, Carmen; Zúñiga, Jesús M.; Vargas, Ronald; Torres, Cristian G.; Tadich, Néstor; Gimpel, Jessica; Martinez, Claudio; Sandoval, Daniel; Enríquez, Ricardo; Alfaro, Julio; Muñoz, Pablo; Paredes, Rodolfo; Erranz, Benjamín; Carvacho, Ingrid; Mezzano, Marcelo; Herrera, Emilio A.La investigación con fauna silvestre tiene diversos propósitos como la conservación de especies, gestión ambiental y generación de conocimiento. El objetivo de los Comités Institucionales de Cuidado y Uso de Animales (CICUAs) es que dicha investigación se realice con altos estándares de bioética y bienestar animal, minimizando el sufrimiento animal y el impacto ambiental. Este artículo destaca la importancia de los CICUAs como un aliado para adecuar los procedimientos con animales a la normativa y facilitar el avance científico.Item Influence of tidal volume on pulse pressure variation and stroke volume variation during experimental intra-abdominal hypertension(BioMed Central Ltd., 2015) Díaz, Franco; Erranz, Benjamín; Donoso, Alejandro; Salomón, Tatiana; Cruces, PabloBACKGROUND: Pulse pressure variation (PPV) and stroke volume variation (SVV) are frequently used to assess fluid responsiveness in critically ill patients on mechanical ventilation (MV). There are many factors, in addition to preload that influence the magnitude of these cyclic variations. We sought to investigate the effect of tidal volume (V(T)) on PPV and SVV, and prediction of fluid responsiveness in a model of intra-abdominal hypertension (IAH). METHODS: Twelve anesthetized and mechanically ventilated piglets on continuous pulse contour cardiac output monitoring. Hypovolemia was ruled out with 2 consecutive fluid boluses after instrumentation. IAH was induced by intraperitoneal instillation of colloid solution with a goal of reducing respiratory system compliance by 50 %. Subjects were classified as fluid responders if stroke volume increased >15 % after each fluid challenge. SVV and PPV were recorded with tidal volumes (VT) of 6, 12 and 18 ml/kg before IAH after IAH induction and after a fluid challenge during IAH. RESULTS: V(T) influenced PPV and SVV at baseline and during IAH, being significantly larger with higher V(T). These differences were attenuated after fluid administration in both conditions. After IAH induction, there was a significant increase in SVV with the three-tested V(T), but the magnitude of that change was larger with high V(T): with 6 ml/kg from 3 % (3, 4) to 5 % (4, 6.25) (p = 0.05), with 12 ml/kg from 5 % (4, 6) to 11 % (8.75, 17) (p = 0.02) and 18 ml/kg from 5 % (4,7.5) to 15 % (8.75, 19.5) (p = 0.02). Similarly, PPV increased with all the tested VT after IAH induction, being this increase larger with high VT: with 6 ml/kg from 3 % (2, 4.25) to 6 % (4.75, 7) (p = 0.05), with 12 ml/kg from 5 % (4, 6) to 13.5 % (10.25, 15.5) (p = 0.02) and 18 ml/kg from 7 % (5.5, 8.5) to 24 % (13.5, 30.25) (p = 0.02). One third of subjects responded to fluid administration after IAH, but neither SVV nor PPV were able to identify the fluid responders with the tested V(T). CONCLUSION: IAH induction in non-hypovolemic subjects significantly increased SVV and PPV with the three tested V(T), but the magnitude of that change was higher with larger V(T). This observation reveals the dependence of functional hemodynamic markers on intrathoracic as well intra-abdominal pressures, in addition to volemic status. Also, PPV and SVV were unable to predict fluid responsiveness after IAH induction. Future studies should take into consideration these findings when exploring relationships between dynamic preload indicators and fluid responsiveness during IAH.Item Mild hypothermia attenuates lung edema and plasma interleukin-1 beta in a rat mechanical ventilation-induced lung injury model(2011) Cruces, Pablo; Ronco, Ricardo; Erranz, Benjamín; Conget, Paulette; Carvajal, Cristóbal; Donoso, Alejandro; Díaz, FrancoRecent data suggest that deep hypothermia has protective effects on experimental induced lung injury. It is not well known if these effects persist with mild hypothermia. The authors hypothesized that mild hypothermia may attenuate lung injury and decrease local and systemic proinflammatory cytokines in a rat model of injurious mechanical ventilation (MV). Twelve Sprague-Dawley male adult rats were anesthetized, intubated, and randomly allocated to normothermia group (37 degrees C) (NT) or mild hypothermia group (34 degrees C) (MH). After 2 hours of deleterious MV (peak inspiratory pressure [PIP] 40 cm H2O, zero end-expiratory pressure [ZEEP], and inspiratory fraction of oxygen [Fio(2)] 100%), arterial blood gases, lung gravimetry, and histological study were obtained. Protein content, interleukin (IL)-1 beta, and tumor necrosis factor (TNF)-alpha were measured in plasma and bronchoalveolar lavage (BAL) fluid. Subjects that underwent MH had a significant lower wet-to-dry lung weight ratio (8.32 +/- 0.28 vs. 10.8 +/- 0.49, P = .01), IL-1 beta plasma concentration (0.6 +/- 0.6 vs. 10.27 +/- 2.80 pg/mL, P = .0048) and Paco(2). There were no differences in terms of Pao(2), histological injury, or BAL protein content. In this model of injurious mechanical ventilation, subjects treated with mild hypothermia had less lung edema and lower plasma IL-1 beta. Some of known beneficial effects of deep hypothermia can be obtained with mild hypothermia.Item Mild hypothermia increases pulmonary anti-inflammatory response during protective mechanical ventilation in a piglet model of acute lung injury(John Wiley & Sons, 2013) Cruces, Pablo; Erranz, Benjamín; Donoso, Donoso; Carvajal, Cristobal; Salomon, Tatiana; Torres, Maria; Diaz, FrancoBACKGROUND: The effects of mild hypothermia (HT) on acute lung injury (ALI) are unknown in species with metabolic rate similar to that of humans, receiving protective mechanical ventilation (MV). We hypothesized that mild hypothermia would attenuate pulmonary and systemic inflammatory responses in piglets with ALI managed with a protective MV. METHODS: Acute lung injury (ALI) was induced with surfactant deactivation in 38 piglets. The animals were then ventilated with low tidal volume, moderate positive end-expiratory pressure (PEEP), and permissive hypercapnia throughout the experiment. Subjects were randomized to HT (33.5°C) or normothermia (37°C) groups over 4 h. Plasma and tissue cytokines, tissue apoptosis, lung mechanics, pulmonary vascular permeability, hemodynamic, and coagulation were evaluated. RESULTS: Lung interleukin-10 concentrations were higher in subjects that underwent HT after ALI induction than in those that maintained normothermia. No difference was found in other systemic and tissue cytokines. HT did not induce lung or kidney tissue apoptosis or influence lung mechanics or markers of pulmonary vascular permeability. Heart rate, cardiac output, oxygen uptake, and delivery were significantly lower in subjects that underwent HT, but no difference in arterial lactate, central venous oxygen saturation, and coagulation test was observed. CONCLUSIONS: Mild hypothermia induced a local anti-inflammatory response in the lungs, without affecting lung function or coagulation, in this piglet model of ALI. The HT group had lower cardiac output without signs of global dysoxia, suggesting an adaptation to the decrease in oxygen uptake and delivery. Studies are needed to determine the therapeutic role of HT in ALI.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 Positive end-expiratory pressure improves elastic working pressure in anesthetized children(2018) Cruces, Pablo; González-Dambrauskas, Sebastián; Cristiani, Federico; Martínez, Javier; Henderson, Ronnie; Erranz, Benjamín; Díaz, FrancoBackground Positive end-expiratory pressure (PEEP) has been demonstrated to decrease ventilator-induced lung injury in patients under mechanical ventilation (MV) for acute respiratory failure. Recently, some studies have proposed some beneficial effects of PEEP in ventilated patients without lung injury. The influence of PEEP on respiratory mechanics in children is not well known. Our aim was to determine the effects on respiratory mechanics of setting PEEP at 5 cmH2O in anesthetized healthy children. Methods Patients younger than 15 years old without history of lung injury scheduled for elective surgery gave informed consent and were enrolled in the study. After usual care for general anesthesia, patients were placed on volume controlled MV. Two sets of respiratory mechanics studies were performed using inspiratory and expiratory breath hold, with PEEP 0 and 5 cmH2O. The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory pressure (PIP), plateau pressure (PPL) and total PEEP (tPEEP) were measured. Respiratory system compliance (CRS), inspiratory and expiratory resistances (RawI and RawE) and time constants (KTI and KTE) were calculated. Data were expressed as median and interquartile range (IQR). Wilcoxon sign test and Spearman’s analysis were used. Significance was set at P < 0.05. Results We included 30 patients, median age 39 (15–61.3) months old, 60% male. When PEEP increased, PIP increased from 12 (11,14) to 15.5 (14,18), and CRS increased from 0.9 (0.9,1.2) to 1.2 (0.9,1.4) mL·kg− 1·cmH2O− 1; additionally, when PEEP increased, driving pressure decreased from 6.8 (5.9,8.1) to 5.8 (4.7,7.1) cmH2O, and QE decreased from 13.8 (11.8,18.7) to 11.7 (9.1,13.5) L·min− 1 (all P < 0.01). There were no significant changes in resistance and QI. Conclusions Analysis of respiratory mechanics in anesthetized healthy children shows that PEEP at 5 cmH2O places the respiratory system in a better position in the P/V curve. A better understanding of lung mechanics may lead to changes in the traditional ventilatory approach, limiting injury associated with MV.Item Predisposición genética y síndrome de distrés respiratorio agudo pediátrico: nuevas herramientas de estudio genético(2015) Erranz, Benjamín; Wilhelm B., Jan; Riquelme V., Raquel; Cruces R, PabloEl síndrome de distrés respiratorio agudo (SDRA) es la forma más grave de falla respiratoria. Teóricamente, cualquier noxa pulmonar aguda puede resultar en un SDRA, pero solo un pequeño porcentaje de individuos desarrolla la enfermedad. Sobre este fundamento, factores genéticos han sido implicados en el riesgo de desarrollar SDRA. Basado en la fisiopatología de esta enfermedad, múltiples genes candidatos han sido evaluados como potenciales modificadores, tanto en pacientes como en modelos animales de SDRA. Datos experimentales y estudios clínicos recientes sugieren que variantes de genes implicados en procesos clave de daño tisular, celular y molecular pulmonar pueden influir en la predisposición y el pronóstico del SDRA. Sin embargo, la patogénesis del SDRA pediátrico es compleja y, en consecuencia, es posible anticipar que muchos genes pueden contribuir a ella. Variantes genéticas, tales como polimorfismos de nucleótido simple y variantes del número de copias, están probablemente asociadas con la predisposición al SDRA en niños con lesión pulmonar primaria. El estudio de asociación del genoma completo (GWAS, del inglés Genome-Wide Association Study) puede examinar estas variantes sin sesgos y ayudar a identificar nuevos genes fundamentales y vías patogénicas clave para futuros análisis. Esta aproximación también puede tener implicancias clínicas diagnósticas y terapéuticas, como predecir el riesgo del paciente o desarrollar un enfoque terapéutico personalizado para este grave síndrome.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.Item Regenerative Potential of Mesenchymal Stromal Cells: Age-Related Changes(Hindawi Publishing Corporation, 2016) Bruna, Flavia; Contador, David; Conget, Paulette; Erranz, Benjamín; Sossa, Claudia; Arango-Rodríguez, MarthaPreclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs) transplant. No systematic information is currently available regarding whether donor age modifies MSC regenerative potential on cutaneous wound healing. Here, we evaluate whether donor age influences this potential. Two different doses of bone marrow MSCs (BM-MSCs) from young, adult, or old mouse donors or two doses of their acellular derivatives mesenchymal stromal cells (acd-MSCs) were intradermally injected around wounds in the midline of C57BL/6 mice. Every two days, wound healing was macroscopically assessed (wound closure) and microscopically assessed (reepithelialization, dermal-epidermal junction, skin appendage regeneration, granulation tissue, leukocyte infiltration, and density dermal collagen fibers) after 12 days from MSC transplant. Significant differences in the wound closure kinetic, quality, and healing of skin regenerated were observed in lesions which received BM-MSCs from different ages or their acd-MSCs compared to lesions which received vehicle. Nevertheless, our data shows that adult’s BM-MSCs or their acd-MSCs were the most efficient for recovery of most parameters analyzed. Our data suggest that MSC efficacy was negatively affected by donor age, where the treatment with adult’s BM-MSCs or their acd-MSCs in cutaneous wound promotes a better tissue repair/regeneration. This is due to their paracrine factors secretionItem Surfactant deactivation in a pediatric model induces hypovolemia and fluid shift to the extravascular lung compartment(John Wiley & Sons, 2013) Diaz, Franco; Erranz, Benjamín; Donoso, Alejandro; Carvajal, Cristobal; Salomon, Tatiana; Torres, Maria; Cruces, PabloBACKGROUND: Surfactant deficiency is the pivotal abnormality in Neonatal and Acute Respiratory Distress Syndrome. Surfactant deactivation can produce hypoxemia, loss of lung compliance, and pulmonary edema, but its circulatory consequences are less understood. OBJECTIVE: To describe the sequential hemodynamic changes and pulmonary edema formation after surfactant deactivation in piglets. METHODS: Surfactant deactivation was induced by tracheal instillation of polysorbate 20 in 15 anesthetized and mechanically ventilated Large White piglets. The hemodynamic consequences of surfactant deactivation were assessed at 30, 120, and 240 min by transpulmonary thermodilution and traditional methods. RESULTS: Surfactant deactivation caused hypoxemia, reduced lung compliance, and progressively increased lung water content (P < 0.01). Early hypovolemia was observed, with reductions of the global end-diastolic volume and stroke volume (P < 0.05). Reduced cardiac output was observed at the end of the study (P < 0.05). Standard monitoring was unable to detect these early preload alterations. Surprisingly, the bronchoalveolar protein content was greatly increased at the end of the study compared with baseline levels (P < 0.01). This finding was inconsistent with the notion that the pulmonary edema induced by surfactant deactivation was exclusively caused by high surface tension. CONCLUSIONS: Hypovolemia develops early after surfactant deactivation, in part due to the resulting fluid shift from the intravascular compartment to the lungs.