Apoptotic mechanisms in rabbits with blast-induced acute lung injury

Abstract Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.

Comparação entre ventilação mecânica convencional protetora e ventilação oscilatória de alta frequência associada à posição prona / Comparison between conventional protective mechanical ventilation and high-frequency oscillatory ventilation associated with the prone position

RESUMO Objetivo: Comparar os efeitos da ventilação oscilatória de alta frequência e da ventilação mecânica convencional protetora associadas à posição prona quanto à oxigenação, à histologia e ao dano oxidativo pulmonar em modelo experimental de lesão pulmonar aguda. Métodos: Foram instrumentados com traqueostomia, acessos vasculares e ventilados mecanicamente 45 coelhos. A lesão pulmonar aguda foi induzida por infusão traqueal de salina aquecida. Foram formados três grupos experimentais: animais sadios + ventilação mecânica convencional protetora, em posição supina (Grupo Controle; n = 15); animais com lesão pulmonar aguda + ventilação mecânica convencional protetora, posição prona (GVMC; n = 15); animais com lesão pulmonar aguda + ventilação oscilatória de alta frequência, posição prona (GVAF; n = 15). Após 10 minutos do início da ventilação específica de cada grupo, foi coletada gasometria arterial, sendo este momento denominado tempo zero, após o qual o animal foi colocado em posição prona, permanecendo assim por 4 horas. O estresse oxidativo foi avaliado pelo método de capacidade antioxidante total. A lesão tecidual pulmonar foi determinada por escore histopatológico. O nível de significância adotado foi de 5%. Resultados: Ambos os grupos com lesão pulmonar aguda apresentaram piora da oxigenação após a indução da lesão comparados ao Grupo Controle. Após 4 horas, houve melhora significante da oxigenação no grupo GVAF comparado ao GVMC. A análise da capacidade antioxidante total no plasma mostrou maior proteção no GVAF. O GVAF apresentou menor escore de lesão histopatológica no tecido pulmonar que o GVMC. Conclusão: A ventilação oscilatória de alta frequência, associada à posição prona, melhora a oxigenação, e atenua o dano oxidativo e a lesão pulmonar histopatológica, comparada com ventilação mecânica convencional protetora.

ABSTRACT Objective: To compare the effects of high-frequency oscillatory ventilation and conventional protective mechanical ventilation associated with the prone position on oxygenation, histology and pulmonary oxidative damage in an experimental model of acute lung injury. Methods: Forty-five rabbits with tracheostomy and vascular access were underwent mechanical ventilation. Acute lung injury was induced by tracheal infusion of warm saline. Three experimental groups were formed: healthy animals + conventional protective mechanical ventilation, supine position (Control Group; n = 15); animals with acute lung injury + conventional protective mechanical ventilation, prone position (CMVG; n = 15); and animals with acute lung injury + high-frequency oscillatory ventilation, prone position (HFOG; n = 15). Ten minutes after the beginning of the specific ventilation of each group, arterial gasometry was collected, with this timepoint being called time zero, after which the animal was placed in prone position and remained in this position for 4 hours. Oxidative stress was evaluated by the total antioxidant performance assay. Pulmonary tissue injury was determined by histopathological score. The level of significance was 5%. Results: Both groups with acute lung injury showed worsening of oxygenation after induction of injury compared with the Control Group. After 4 hours, there was a significant improvement in oxygenation in the HFOG group compared with CMVG. Analysis of total antioxidant performance in plasma showed greater protection in HFOG. HFOG had a lower histopathological lesion score in lung tissue than CMVG. Conclusion: High-frequency oscillatory ventilation, associated with prone position, improves oxygenation and attenuates oxidative damage and histopathological lung injury compared with conventional protective mechanical ventilation.

Decreased lung compliance increases preload dynamic tests in a pediatric acute lung injury model / Una compliance pulmonar disminuida incrementa los test dinámicos de precarga en un modelo pediátrico de lesión pulmonar aguda

Background: 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 (V T) 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 ± 0.4 kg) were anesthetized, paralyzed and monitored with pulse contour analysis. PPV and SVV were recorded during mechanical ventilation with a V T of 6 and 12 mL/kg (low and high V T, respectively), both before and after tracheal instillation of polysorbate 20. Results: Before acute lung injury (ALI) induction, modifications of V T did not significantly change PPV and SVV readings. After ALI, PPV and SVV were significantly greater during ventilation with a high V T compared to a low V T (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 V T 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.

Introducción: Test dinámicos de precarga, variación de presión de pulso (PPV) y variación de volumen sistólico (SVV) han emergido como herramientas poderosas para predecir respuesta a la administración de fluidos. Actualmente la influencia de factores distintos a la precarga en la determinación de los test dinámicos de precarga es pobremente conocida en pediatría. Nuestro objetivo fue medir el efecto del volumen tidal (V T) sobre PPV y SVV en un contexto de compliance pulmonar normal y disminuida en un modelo porcino. Material y método: Veinte cerditos Large-White anestesiados y paralizados (5,2 ± 0,4 kg). PPV y SVV fueron medidos por análisis de contorno de pulso durante ventilación con V T de 6 y 12 mL/kg (V T bajo y alto, respectivamente), ambos previo y posterior a lesión pulmonar aguda (ALI) químicamente inducida con instilación traqueal de polisorbato 20. Resultados: Previo a inducción de ALI, PPV y SVV no tuvieron cambios significativos al modificar el V T. Sin embargo, después de ALI, PPV y SVV fueron significativamente mayores durante ventilación con V T alto, respecto a V T bajo (PPV aumentó de 8,9 ± 1,2 a 12,4 ± 1,1%, y SVV de 8,5 ± 1,0 a 12,7 ± 1,2%, ambos P < 0,01). Conclusiones: Este estudio encontró que un V T alto y una compliance pulmonar disminuida debido a ALI incrementan los test dinámicos de precarga, con una mayor influencia de esta última. En sujetos con ALI la compliance pulmonar debiera ser considerada al interpretar los test dinámicos de precarga.

Postperfusion lung syndrome: physiopathology and therapeutic options / Síndrome pós-perfusão pulmonar: fisiopatologia e opções terapêuticas

Postperfusion lung syndrome is rare but can be lethal. The underlying mechanism remains uncertain but triggering inflammatory cascades have become an accepted etiology. A better understanding of the pathophysiology and the roles of inflammatory mediators in the development of the syndrome is imperative in the determination of therapeutic options and promotion of patients' prognosis and survival. Postperfusion lung syndrome is similar to adult respiratory distress syndrome in clinical features, diagnostic approaches and management strategies. However, the etiologies and predisposing risk factors may differ between each other. The prognosis of the postperfusion lung syndrome can be poorer in comparison to acute respiratory distress syndrome due to the secondary multiple organ failure and triple acid-base imbalance. Current management strategies are focusing on attenuating inflammatory responses and preventing from pulmonary ischemia-reperfusion injury. Choices of cardiopulmonary bypass circuit and apparatus, innovative cardiopulmonary bypass techniques, modified surgical maneuvers and several pharmaceutical agents can be potential preventive strategies for acute lung injury during cardiopulmonary bypass.

Síndrome pós-perfusão pulmonar é rara, mas pode ser letal. O mecanismo subjacente permanece incerto, mas desencadear cascatas inflamatórias tornou-se uma etiologia aceita. É imperativo uma melhor compreensão da fisiopatologia e os papéis de mediadores inflamatórios no desenvolvimento da síndrome na determinação de opções terapêuticas e de promoção do prognóstico e sobrevida dos pacientes. Síndrome pós-perfusão pulmonar é semelhante à síndrome da angústia respiratória do adulto em características clínicas, métodos diagnósticos e estratégias de gestão. No entanto, as etiologias e fatores de risco predisponentes podem ser diferentes entre si. O prognóstico da síndrome pós-perfusão pulmonar pode ser mais pobres em comparação com síndrome da angústia respiratória aguda, devido à falência de múltiplos órgãos secundária e desequilíbrio ácido-base triplo. Estratégias de gestão atuais centram-se em atenuar reações inflamatórias e impedir lesão pulmonar de isquemia-reperfusão. Escolhas do circuito de circulação extracorpórea e aparelhos, técnicas inovadoras de circulação extracorpórea, manobras cirúrgicas modificadas e vários agentes farmacêuticos podem ser potenciais estratégias preventivas para lesão pulmonar aguda durante a circulação extracorpórea.

Mechanical ventilation and volutrauma: study in vivo of a healthy pig model

Mechanical ventilation is essential in intensive care units. However, it may itself induce lung injury. Current studies are based on rodents, using exceptionally large tidal volumes for very short periods, often after a "priming" pulmonary insult. Our study deepens a clinically relevant large animal model, closely resembling human physiology and the ventilator setting used in clinic settings. Our aim was to evaluate the pathophysiological mechanisms involved in alveolo/capillary barrier damage due to mechanical stress in healthy subjects. We randomly divided 18 pigs (sedated with medetomidine/tiletamine-zolazepam and anesthetised with thiopental sodium) into three groups (n=6): two were mechanically ventilated (tidal volume of 8 or 20 ml/kg), the third breathed spontaneously for 4 hours, then animals were sacrificed (thiopental overdose). We analyzed every 30' hemogasanalysis and the main circulatory and respiratory parameters. Matrix gelatinase expression was evaluated on bronchoalveolar lavage fluid after surgery and before euthanasia. On autoptic samples we performed zymographic analysis of lung, kidney and liver tissues and histological examination of lung. Results evidenced that high Vt evoked profound alterations of lung mechanics and structure, although low Vt strategy was not devoid of side effects, too. Unexpectedly, also animals that were spontaneously breathing showed a worsening of the respiratory functions.

Estabilidade do modelo animal de lesão pulmonar aguda induzida por ácido oleico / Stability of the animal model of oleic acid-induced acute lung injury

OBJETIVO: Avaliar a estabilidade das variáveis hemodinâmicas, da mecânica respiratória e de troca gasosa do modelo animal de lesão pulmonar aguda induzida por ácido oleico. MÉTODOS: Trata-se de um estudo experimental no qual foram utilizados 10 cães de raça indeterminada. As variáveis foram aferidas inicialmente e em 30, 60, 90 e 120 min após a administração do ácido oleico. Para analisar as medidas repetidas, foram testados efeitos lineares e quadráticos e foram utilizados ajustes de modelos lineares mistos com estruturas de variâncias e covariâncias diversificadas, dependendo da variável analisada. RESULTADOS: Observamos estabilidade da pressão arterial média aos 30 min, assim como da frequência cardíaca, da pressão arterial pulmonar e da pressão de capilar pulmonar aos 60 min. Frequência respiratória, volume corrente, volume minuto e trabalho respiratório estabilizaram aos 30 min. Quanto às variáveis de troca gasosa, PaO2, relação PaO2/FiO2 e fração de shunt pulmonar estabilizaram-se aos 30 min. As demais variáveis mantiveram-se em ascensão ou queda contínuas. CONCLUSÕES: O modelo de lesão pulmonar aguda induzida por ácido oleico é estável para algumas das variáveis testadas; porém, a estabilização se dá em momentos diferentes. As variáveis da mecânica respiratória e de troca gasosa estabilizaram em 30 min, e as hemodinâmicas, em 60 min.

OBJECTIVE: To evaluate the stability of hemodynamic, respiratory and gas exchange variables in an animal model of oleic acid-induced acute lung injury. METHODS: This was an experimental study involving 10 mongrel dogs. The variables were measured at baseline, as well as at 30, 60, 90 and 120 min after the administration of oleic acid. In order to analyze repeated measurements, linear and quadratic effects were tested. Mixed linear models with diversified variance and covariance structures were used, depending on the variable studied. RESULTS: We found that mean arterial blood pressure stabilized at 30 min, as did heart rate, pulmonary arterial pressure and pulmonary capillary pressure at 60 min. Respiratory rate, tidal volume, minute volume and respiratory work stabilized at 30 min. Regarding gas exchange variables, PaO2, PaO2/FiO2 ratio and pulmonary shunt fraction stabilized at 30 min. The remaining variables maintained a continuous rise or fall. CONCLUSIONS: This oleic acid-induced acute lung injury model is stable for some of the variables tested, although stabilization occurs at different times. The respiratory and gas exchange variables stabilized at 30 min, whereas the hemodynamic variables stabilized at 60 min.