Research progress on mechanism of biotrauma caused by ventilation-induced lung injury / 中华危重病急救医学

Mechanical ventilation is an advanced life support treatment for patients with acute respiratory failure. While stabilizing respiratory function, it also acts as an injury factor to exacerbate or lead to lung injury, that is, ventilation-induced lung injury (VILI). There may be a more subtle form of damage to VILI known as "biotrauma". However, the mechanism of biotrauma in VILI is still unclear. This article intends to review the mechanism of biotrauma of VILI from the aspects of inflammatory response, oxidative stress and complement activation, in order to provide a new strategy for clinical prevention and treatment of biotrauma caused by VILI.

Role of glutamine in the mediation of E-cadherin, p120-catenin and inflammation in ventilator-induced lung injury / 中华医学杂志(英文版)

<p><b>Background</b>Ventilator-induced lung injury (VILI) is commonly associated with barrier dysfunction and inflammation reaction. Glutamine could ameliorate VILI, but its role has not been fully elucidated. This study examined the relationship between inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and IL-10) and adherens junctions (E-cadherin, p120-catenin), which were ameliorated by glutamine in VILI, both in vitro and in vivo.</p><p><b>Methods</b>For the in vivo study, 30 healthy C57BL/6 mice weighing 25-30 g were randomly divided into five groups with random number table (n = 6 in each group): control (Group C); low tidal volume (Group L); low tidal volume + glutamine (Group L + G); high tidal volume (Group H); and high tidal volume + glutamine (Group H + G). Mice in all groups, except Group C, underwent mechanical ventilation for 4 h. For the in vitro study, mouse lung epithelial 12 (MLE-12) cells pretreated with glutamine underwent cyclic stretching at 20% for 4 h. Cell lysate and lung tissue were obtained to detect the junction proteins, inflammatory cytokines, and lung pathological changes by the Western blotting, cytokine assay, hematoxylin and eosin staining, and immunofluorescence.</p><p><b>Results</b>In vivo, compared with Group C, total cell counts (t = -28.182, P < 0.01), the percentage of neutrophils (t = -28.095, P < 0.01), IL-6 (t = -28.296, P < 0.01), and TNF-α (t = -19.812, P < 0.01) in bronchoalveolar lavage (BAL) fluid, lung injury scores (t = -6.708, P < 0.01), and the wet-to-dry ratio (t = -15.595, P < 0.01) were increased in Group H; IL-10 in BAL fluid (t = 9.093, P < 0.01) and the expression of E-cadherin (t = 10.044, P < 0.01) and p120-catenin (t = 13.218, P < 0.01) were decreased in Group H. Compared with Group H, total cell counts (t = 14.844, P < 0.01), the percentage of neutrophils (t = 18.077, P < 0.01), IL-6 (t = 18.007, P < 0.01), and TNF-α (t = 10.171, P < 0.01) in BAL fluid were decreased in Group H + G; IL-10 in BAL fluid (t = -7.531, P < 0.01) and the expression of E-cadherin (t = -14.814, P < 0.01) and p120-catenin (t = -9.114, P < 0.01) were increased in Group H + G. In vitro, compared with the nonstretching group, the levels of IL-6 (t = -21.111, P < 0.01) and TNF-α (t = -15.270, P < 0.01) were increased in the 20% cyclic stretching group; the levels of IL-10 (t = 5.450, P < 0.01) and the expression of E-cadherin (t = 17.736, P < 0.01) and p120-catenin (t = 16.136, P < 0.01) were decreased in the 20% cyclic stretching group. Compared with the stretching group, the levels of IL-6 (t = 11.818, P < 0.01) and TNF-α (t = 8.631, P < 0.01) decreased in the glutamine group; the levels of IL-10 (t = -3.203, P < 0.05) and the expression of E-cadherin (t = -13.567, P < 0.01) and p120-catenin (t = -10.013, P < 0.01) were increased in the glutamine group.</p><p><b>Conclusions</b>High tidal volume mechanical ventilation and 20% cyclic stretching could cause VILI. Glutamine regulates VILI by improving cytokines and increasing the adherens junctions, protein E-cadherin and p120-catenin, to enhance the epithelial barrier function.</p>

Ventilación de alta frecuencia oscilatoria en pediatría / High frequency oscillatory ventilation in pediatrics

Mechanical ventilation (MV) is a usual therapy for the management of critically ill children. However its inappropriate use can produce lung injury. Today, the evidence recommends protective ventilation such as strategie low tidal volumes (VT) that minimize injury and thus, high frequency oscillatory ventilation (HFOV) would have a theoretical role. HFOV allows gas exchange using low tidal volumes (1 – 2 ml/kg) and supraphysiologic respiratory frequencies. In pediatrics it comprises 3 – 30 percent of mechanically ventilated patients, most of the time as a rescue therapy in refractory respiratory failure cases where conventional mechanical ventilation fails. Many aspects of HFVO in children remain unclear, theoretical benefits has no solid clinical basis, when is the best time to initiate (early vs rescue mode), which are the optimal settings, and how to monitor lung mechanics. This review examines HFVO theoretical bases, suggest recommendations for its use and considers the available evidence to understand the aspects that are still unclear.

La ventilación mecánica (VM) constituye un apoyo frecuente en el manejo de niños críticamente enfermos, quienes pueden requerirla por diferentes etiologías, entre ellas el síndrome de dificultad respiratoria aguda (SDRA). Sabemos que a pesar de ser un soporte vital, su uso inapropiado puede producir daño inducido por ventilación mecánica (DIVM). En la actualidad, la evidencia recomienda las estrategias de “ventilación protectora”, bajos volúmenes corrientes, que minimicen este daño y es ahí donde la ventilación de alta frecuencia oscilatoria (VAFO) tendría un rol teórico. La VAFO permite el intercambio gaseoso usando pequeños volúmenes corrientes (VT) 1-2 ml /kg y frecuencias respiratorias supra fisiológicas, con la consiguiente disminución del riesgo de atelectrauma, manteniendo el “pulmón abierto” y en la zona de seguridad de la curva presión-volumen. Su uso en pediatría oscila entre el 3 y el 30 por ciento de los pacientes ventilados, la mayoría de las veces como terapia de rescate frente a la falla de la ventilación convencional (VMC) en insuficiencia respiratoria refractaria. Muchos aspectos de la VAFO en pediatría no han sido totalmente esclarecidos; su efecto protector teórico permanece aún sin bases sólidas en el escenario clínico, quienes se benefician de su uso, cuál es el mejor momento para iniciarla (temprana o rescate), cuales son los valores óptimos del oscilador y como monitorear la mecánica pulmonar en VAFO. La presente revisión pretende repasar los conceptos teóricos de la VAFO, formular recomendaciones para su uso y considerar la evidencia disponible que nos permitan dilucidar las interrogantes antes mencionadas.

Research on the effect of protection against ventilator-induced lung injury via regulation of caveolin-1/heme oxygenase-1 signaling / 中华危重病急救医学

ObjectiveTo determine whether the inhibition of caveolin-1 tyrosine residues 14 (Cav-1-Y14) phosphorylation with protein tyrosine kinase inhibitors (PP2) will upregulate heme oxygenase-1 (HO-1) activity to protect against ventilation induced lung injury in vivo of an animal model.Methods Fifty-four male Sprague-Dawley (SD) rats were randomly divided into nine groups (eachn = 6). Group A served as normal control group, in which rats did not receive ventilation but tracheotomy. Groups B1 and B2 received lung protective ventilation respectively for 1 hour or 2 hours. Groups C1 and C2 received high tidal volume (40 mL/kg) ventilation for 1 hour or 2 hours, respectively. The group D1 or D2 also received high tidal volume ventilation for 1 hour or 2 hour respectively, but they were given PP2 1 hour before high tidal volume ventilation. The groups E1 and E2 also received high tidal volume ventilation respectively for 1 hour or 2 hours, but tyrosine kinase inhibitor PP2 and HO-1 inhibitor zinc protoporphyrinⅨ(ZnPPⅨ) were given to animals 18 hours before high tidal volume ventilation. All the animals were sacrificed after ventilation, and the specimens of lung tissues and bronchoalveolar lavage fluid (BALF) were harvested. Then the changes in pathology of lung tissue was observed, and diffuse alveolar damage scores (DAD) were calculated, myeloperoxidase (MPO) activity was measured by colorimetric analysis, lung wet/dry ratio (W/D) was estimated. The expressions of phosphorylated caveolin-1 (P-Cav-1-Y14), caveolin-1 (Cav-1) and HO-1 were determined by Western Blot. The expressions of high mobility group B1 (HMGB1) and advanced glycation end product receptor (RAGE) in lung tissues were assayed with immunohistochemistry staining. The levels of tumor necrosis factor-α(TNF-α) in BALF were measured by enzyme linked immunosorbent assay (ELISA).Results There was no significant difference in all the parameters between group A and groups B. Compared with group B1, DAD score, W/D ratio, the activity of MPO and the concentration of TNF-α in BALF in group C1 were significantly increased [DAD score:7.97±0.59 vs. 0.55±0.13, W/D ratio: 5.70±1.61 vs. 5.04±0.63, MPO (U/g): 1.82±0.14 vs. 0.77±0.26, TNF-α(ng/L): 370.10±29.61 vs. 54.38±8.18, allP< 0.05], and the injury in ventilation 2 hours group was more serious than that in ventilation 1 hour group. Compared with groups C, all the parameters in groups D were significantly decreased. The parameters in groups E were significantly higher than those in groups A, B, and D, but no significant difference was found as compared with groups C. Compared with groups B, the protein expressions of Cav-1 and P-Cav-1-Y14 (gray value) in groups C were significantly increased (1 hour: 1.49±0.02 vs. 1.26±0.13, 1.34±0.02 vs. 0.87±0.04;2 hours: 1.58±0.02 vs. 1.27±0.27, 1.31±0.01 vs. 0.95±0.02, allP< 0.05), and the expression of HO-1 protein (gray value) was significantly decreased (1 hour: 0.59±0.02 vs. 1.10±0.01, 2 hours: 0.49±0.01 vs. 1.20±0.02, both P< 0.05). No significant difference in Cav-1 protein expression between groups D as well as groups E and groups C. The protein expression of P-Cav-1-Y14 in groups D and E was significantly lower than that in groups C. The protein expression of HO-1 in groups D was significantly higher than that in groups C, but the phenomenon was not found in groups E as compared with groups C. Compared with group A, the positive expression of HMGB1 and RAGE in lung tissue in groups C and E was significantly increased, but no significant difference was found between groups B as well as groups D and group A.Conclusion Cav-1-Y14 phosphorylation is the key factor for ventilator induced lung injury, which can not only lead to a decrease in vascular barrier function, but also inhibit the activity of HO-1 enzyme, thus further aggravates inflammatory injury of the lung as induced by mechanical ventilation.

Ventilator-Induced Lung Injury / 대한주산의학회잡지

Positive pressure ventilation (PPV) is one of the most commonly used treatment modalities in the field of neonatology to achieve adequate gas exchange for infants with respiratory difficulties. However, mechanical ventilation may cause lung injury through various mechanisms, including high airway pressure and high tidal volume, leading to acute respiratory distress syndrome, bronchopulmonary dysplasia or multiple organ failure. To prevent these injuries, clinicians, especially neonatologists, treating premature infants with respiratory distress syndrome, should be familiar with ventilator-induced lung injury and its preventive strategies. In this review, the mechanisms of lung injury, the effects of mechanical ventilation on pulmonary microvascular endothelium, extracelluar matrix and alveolar epithelium, and lung protective strategies of conventional ventilation are introduced. Several forms of conventional ventilation for preterm infants are also described.

Utilization of the lower inflection point of the pressure-volume curve results in protective conventional ventilation comparable to high frequency oscillatory ventilation in an animal model of acute respiratory distress syndrome

INTRODUCTION: Studies comparing high frequency oscillatory and conventional ventilation in acute respiratory distress syndrome have used low values of positive end-expiratory pressure and identified a need for better recruitment and pulmonary stability with high frequency. OBJECTIVE: To compare conventional and high frequency ventilation using the lower inflection point of the pressure-volume curve as the determinant of positive end-expiratory pressure to obtain similar levels of recruitment and alveolar stability. METHODS: After lung lavage of adult rabbits and lower inflection point determination, two groups were randomized: conventional (positive end-expiratory pressure = lower inflection point; tidal volume=6 ml/kg) and high frequency ventilation (mean airway pressures= lower inflection point +4 cmH2O). Blood gas and hemodynamic data were recorded over 4 h. After sacrifice, protein analysis from lung lavage and histologic evaluation were performed. RESULTS: The oxygenation parameters, protein and histological data were similar, except for the fact that significantly more normal alveoli were observed upon protective ventilation. High frequency ventilation led to lower PaCO2 levels. DISCUSSION: Determination of the lower inflection point of the pressure-volume curve is important for setting the minimum end expiratory pressure needed to keep the airways opened. This is useful when comparing different strategies to treat severe respiratory insufficiency, optimizing conventional ventilation, improving oxygenation and reducing lung injury. CONCLUSIONS: Utilization of the lower inflection point of the pressure-volume curve in the ventilation strategies considered in this study resulted in comparable efficacy with regards to oxygenation and hemodynamics, a high PaCO2 level and a lower pH. In addition, a greater number of normal alveoli were found after protective conventional ventilation in an animal model of acute respiratory distress syndrome.