PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.
Animals ; Lung Injury/etiology* ; Blast Injuries ; Goats ; Explosions ; Lung/pathology*

Sepsis is one of the most common pathogenetic causes of acute lung injury (ALI), and at present there is still a lack of effective targeted techniques and methods for its prevention and treatment. Autophagy is a homeostatic mecha- nism common to all eukaryotic cells, including adaption to environment, defense against invasion of pathogens, and maintenance of cellular homeostasis. Autophagy is also involved in a variety of lung-related diseases. In septic lung injury, autophagy not only serves to dissipate dysfunctional organelles, but also inhibits the release of inflammatory cytokines. This review aims at eliciting the role of autophagy in sepsis-induced ALI and further exploring the potential targets of autophagy in inhibiting inflammation, in an effort to provide a new perspective for clinical treatment of sepsis-induced ALI.
Acute Lung Injury ; etiology ; metabolism ; Autophagy ; Cytokines ; metabolism ; Inflammation ; metabolism ; Lung ; metabolism ; Lung Injury ; Sepsis ; complications ; metabolism

Acute Lung Injury ; epidemiology ; etiology ; therapy ; Humans ; Respiratory Distress Syndrome, Adult ; epidemiology ; etiology ; therapy

OBJECTIVES: To study the role of the low-density lipoprotein receptor-related protein 1 (LRP1)-proline-rich tyrosine kinase 2 phosphorylation (pPyk2)-matrix metalloproteinases 9 (MMP9) pathway in hyperoxia-induced lung injury in neonatal rats. METHODS: A total of 16 neonatal rats were randomly placed in chambers containing room air (air group) or 95% medical oxygen (hyperoxia group) immediately after birth, with 8 rats in each group. All of the rats were sacrificed on day 8 of life. Hematoxylin and eosin staining was used to observe the pathological changes of lung tissue. ELISA was used to measure the levels of soluble LRP1 (sLRP1) and MMP9 in serum and bronchoalveolar lavage fluid (BALF). Western blot was used to measure the protein expression levels of LRP1, MMP9, Pyk2, and pPyk2 in lung tissue. RT-PCR was used to measure the mRNA expression levels of LRP1 and MMP9 in lung tissue. RESULTS: The hyperoxia group had significantly higher levels of sLRP1 and MMP9 in serum and BALF than the air group ( CONCLUSIONS The activation of the LRP1-pPyk2-MMP9 pathway is enhanced in hyperoxia-induced lung injury in neonatal rats, which may be involved in the pathogenesis of bronchopulmonary dysplasia.
Animals ; Animals, Newborn ; Hyperoxia/complications* ; Lung ; Lung Injury/etiology* ; Matrix Metalloproteinase 9/genetics* ; Rats

OBJECTIVE: To explore the influence of intraoperative urine volume on postoperative acute kidney injury (AKI) and the independent risk factors of AKI. METHODS: This was a retrospective cohort study recruiting patients who received selective pulmonary resection under general anesthesia in Peking University First Hospital from July, 2017 to June, 2019. The patients were divided into the AKI group and the control group according to whether they developed postoperative AKI or not. Firstly, univariate analysis was used to analyze the relationship between perioperative variables and postoperative AKI. Secondly, receiver operating characteristic (ROC) curve was used to explore the predictive value of intraoperative urine output for postoperative AKI. The nearest four cutoff values [with the interval of 0.1 mL/(kg·h)] at maximum Youden index were used as cutoff values of oliguria. Then univariate analysis was used to explore the relationship between oliguria defined by these four cutoff values and the risk of AKI. And the cutoff value with maximum OR was chosen as the threshold of oliguria in this study. Lastly, the variables with P < 0.10 in the univariate analysis were selected for inclusion in a multivariate Logistic model to analyze the independent predictors of postoperative AKI. RESULTS: A total of 1 393 patients were enrolled in the study. The incidence of postoperative AKI was 2.2%. ROC curve analysis showed that the area under curve (AUC) of intraoperative urine volume used for predicting postoperative AKI was 0.636 (P=0.009), and the cutoff value of oliguria was 0.785 mL/(kg·h) when Youden index was maximum (Youden index =0.234, sensitivity =48.4%, specificity =75.0%). Furthermore, 0.7, 0.8, 0.9, 1.0 mL/(kg·h) and the traditional cutoff value of 0.5 mL/(kg·h) were used to analyze the influence of oliguria on postoperative AKI. Univariate analysis showed that, when 0.8 mL/(kg·h) was selected as the threshold of oliguria, the patients with oliguria had the most significantly increased risk of AKI (AKI group 48.4% vs. control group 25.3%, OR=2.774, 95%CI 1.357－5.671, P=0.004). Multivariate regression analysis showed that intraoperative urine output < 0.8 mL/(kg·h) was one of the independent risk factors of postoperative AKI (OR=2.698, 95%CI 1.260－5.778, P=0.011). The other two were preoperative hemoglobin ≤120.0 g/L (OR=3.605, 95%CI 1.545－8.412, P=0.003) and preoperative estimated glomerular filtration rate < 30 mL/(min·1.73 m²) (OR=11.009, 95%CI 1.813－66.843, P=0.009). CONCLUSION Oliguria is an independent risk fact or of postoperative AKI after pulmonary resection, and urine volume < 0.8 mL/(kg·h) is a possible screening criterium.
Acute Kidney Injury/etiology* ; Humans ; Lung ; Oliguria/etiology* ; Postoperative Complications/etiology* ; Postoperative Period ; Retrospective Studies ; Risk Factors

Adequate pulmonary function is pivotal for preterm infants. Besides being structurally immature, the preterm lung is susceptible to injury resulting from different prenatal conditions and postnatal insults. Lung injury might result in impaired postnatal lung development, contributing to chronic lung disease of prematurity, bronchopulmonary dysplasia (BPD). This review focuses on lung injury mediated by and related to inflammatory changes in the lung. We give an overview on experimental models which have helped to elucidate mechanisms of pulmonary inflammation in prematurity. We describe experimental data linking acute and chronic chorioamnionitis with intrapulmonary inflammation, lung maturation and surfactant production in various animal models. In addition, experimental data has shown that fetal inflammatory response is modulated by the fetus himself. Experimental data has therefore helped to understand differential effects on lung function and lung maturation exerted by maternal administration of potentially anti-inflammatory substances like glucocorticosteroids (GCS). New approaches of modulation of pulmonary inflammation/injury caused by postnatal interventions during resuscitation and mechanical ventilation have been studied in animal models. Postnatal therapeutic interventions with widely used drugs like oxygen, steroids, surfactant, caffeine and vitamin A have been experimentally and mechanistically assessed regarding their effect on pulmonary inflammation and lung injury. Carefully designed experiments will help to elucidate the complex interaction between lung injury, lung inflammation, repair and altered lung development, and will help to establish a link between lung alterations originating in this early period of life and long-term adverse respiratory effects.
Acute Lung Injury ; etiology ; Animals ; Chorioamnionitis ; Chronic Disease ; Female ; Glucocorticoids ; adverse effects ; Humans ; Infant, Newborn ; Inflammation ; complications ; Lung Injury ; etiology ; Pregnancy ; Respiration, Artificial ; adverse effects

BACKGROUND: Adverse transfusion reactions (ATRs) are clinically relevant to patients with significant morbidity and mortality. This study aimed to review the cases of ATR reported in the recipient-triggered trace back system for a recent nine-year period in Korea. METHODS: Nine-year data obtained from 2006 to 2014 by the trace back system at the Division of Human Blood Safety Surveillance of the Korean Centers for Disease Control (KCDC) were reviewed. The suspected cases were assessed according to six categories: (i) related to, (ii) probably related to, (iii) probably not related to, (iv) not related to transfusion, (v) unable to investigate, and (vi) under investigation. RESULTS: Since 2006, 199 suspected serious ATRs were reported in hospitals and medical institutions in Korea, and these ATRs were reassessed by the division of Human Blood Safety Surveillance of the KCDC. Among the reported 193 cases as transfusion related infections, hepatitis C virus (HCV) infection (135, 67.8%) was reported most frequently, followed by hepatitis B virus (HBV) infection (27, 13.6%), HIV infection (13, 6.5%), syphilis (9, 4.5%), malarial infection (4, 2.0%), other bacterial infections (3, 1.5%), HTLV infection (1, 0.5%), and scrub typhus infection (1, 0.5%), respectively. Of the 199 cases, 13 (6.5%) cases were confirmed as transfusion-related (3 HCV infections, 3 malarial infections, 1 HBV infection, 2 Staphylococcus aureus sepsis, 3 transfusion-related acute lung injuries, and 1 hemolytic transfusion reaction). CONCLUSIONS: This is the first nationwide data regarding serious ATRs in Korea and could contribute to the implementation of an effective hemovigilance system.
Acute Lung Injury/epidemiology/etiology ; Blood Transfusion/*adverse effects ; HIV Infections/epidemiology/etiology ; Hepatitis C/epidemiology/etiology ; Humans ; Malaria/epidemiology/etiology ; Republic of Korea ; Retrospective Studies ; Transfusion Reaction/*etiology

OBJECTIVETo observe the pathological change of partial liquid ventilation (PLV) through establishing the rabbit model of acute lung injury (ALI) induced by meconium aspiration.

METHODSAdult, healthy male or female New Zealand white rabbits were randomly allocated into six groups as follows: (1) control group, (2) conventional mechanical ventilation (CMV) group, (3) high-frequency oscillatory ventilation (HFOV) group, (4) CMV combined with PLV group, (5) HFOV combined with PLV group and (6) normal group. The animals were anesthetized with 1% pentobarbital and tracheotomy was performed and endotracheal tube was placed, 20% meconium fluid (3 ml/kg) was quickly injected into the lung through the endotracheal tube and arterial blood gas was analyzed 30 minutes later. ALI was indicated when P/F ratio (PaO2)/FiO(2)) was < or = 300 mm Hg (1 mm Hg = 0.133 kPa) and Cdyn Dynamic Compliance declined by more than 30% of the baseline. The animals were then randomly allocated into one of the 6 groups. In PLV groups (including CMV + PLV and HFOV + PLV) warmed (37 degrees C) and oxygenated perfluorocarbon was slowly instilled into the lungs of the rabbits through the endotracheal tube at a low-dose 3 ml/kg, then set 15-min positive pressure by sacculus proprius to guarantee perfluorocarbon to steadily diffuse in to the lungs. Six hours after ventilation the animals were sacrificed by using overdose of room air instillation via vein. The lungs were taken and fixed in 4% paraformaldehyde (PFA) and were stained with hematoxylin-eosin (HE). Pathological evaluations included inflammatory manifestation, edema and hemorrhage in both alveolar and interstitial area, damages of small airway (alveolar tube and alveolar bursa) and hyaline membrane formation. One way analysis of variance, Student Newman-Keuls (SNK) method and Kruskal-Wallis (K-W) test were used for comparisons.

RESULTSWith the exception of normal group 30 minutes after meconium injections blood gas analysis in different groups showed significant changes and PaO(2)/FiO(2) (< 300 mm Hg), Cdyn declined by more than 60% compared with baseline (P < 0.05). The pathological analysis showed that alveolar and interstitial inflammation, edema, alveolar and interstitial hemorrhage, and small airway damage existed in each group. The hyaline membrane formation was found in one of CMV + PLV group rabbits. The perfluorocarbon-treated animals (CMV + PLV and HFOV + PLV) showed significantly less injury in dependent lung and less damage of small airway (CMV + PLV or HFOV + PLV vs. CMV = 1.1 +/- 0.4 or 0.9 +/- 0.3 vs 2.6 +/- 0.5) compared with the animals of CMV group (P < 0.01). HFOV group (2.1 +/- 0.3) also had less alveolar and interstitial inflammation compared with CMV group (3.0 +/- 0) (P < 0.05), and there was less evidence of alveolar and interstitial edema in the animals treated with HFOV + PLV (1.0 +/- 0.7) compared with CMV (2.0 +/- 0.8) (P < 0.01). Treatment with perfluorocarbon did not result in significant difference in alveolar and interstitial hemorrhage. Compared with CMV and HFOV groups, the groups treated with PLV showed lower mortality of animals (21.4% and 14.3%).

CONCLUSIONSPLV can alleviate the histological damage of acute lung injury induced by meconium aspiration and increased survival chance and therefore PLV would be a useful treatment for MAS. The effectiveness and safety of application of PLV should be evaluated in clinical studies.

Acute Lung Injury ; etiology ; pathology ; Animals ; Animals, Newborn ; Disease Models, Animal ; Female ; Liquid Ventilation ; Male ; Rabbits

Burns and traumas are common injuries during both peace time and wartime. Lung is the earliest organ subjected to dysfunction and the incidence is highest. The systemic protective technology for the burn and trauma related lung injuries is based on evidence-based medicine and translational medicine. It includes a series of effective measures, such as rescue and treatment scheme for massive burn casualties, prophylactic tracheostomy, protective ventilation strategy, sequential cell protection, and prevention and treatment of sequelae, which prevents aggravation of lung injuries caused by ischemia reperfusion, oxidative stress, and iatrogenic factors, as well as reduces the incidence of complications to ensure the recovery after burns and traumas.
Burns ; complications ; Evidence-Based Medicine ; Humans ; Lung Injury ; etiology ; prevention & control ; Translational Medical Research

OBJECTIVETo investigate the effect of continuous veno-venous hemodiafiltration (CVVHDF) on endotoxin-induced acute lung injury (ALI) of piglets.

METHODSEighteen piglets were randomly divided into three groups: control group (n = 6); heparin group (n = 6) and CVVHDF treatment group (n = 6). All the animals were anesthetized by muscle injection of ketamine (30 mg/kg), then placed in supine position, received continuous intravenous infusion of ketamine with the rate of 10 mg/(kgxh). After placing a 4.5 cm (inner diameter) tracheal tube via tracheostoma, controlled mechanical ventilation was established using the assisted-controlled ventilation option of the NEWPORT 200. Respiratory rate at 30 breath/min; PIP at 10 cm H2O (1 cm H2O = 0.098 kPa); PEEP at 2 cm H2O and fraction of inspired oxygen at 0.3. A vein catheter was placed into right vena jugularis interna to administer a Ringer's solution. Initially, at a rate of 10 ml/kg, followed by a rate of 15 ml/kg when the mean arterial blood pressure was below 70 mm Hg (1 mm Hg = 0.133 kPa), the rate of 20 ml/kg was used when the mean arterial blood pressure was below 60 mm Hg. An 8Fr double-lumen catheter was inserted into left femoral vein and served as the pathway for CVVHDF. A Pulsiocath Pcco catheter was positioned into left femoral artery to monitor the circulatory parameters. All catheters were flushed with heparinized saline to prevent clotting. Then all the animals were given intravenous infusion of 150 microg/kg endotoxin within 30 minutes to induce ALI. When the oxygenation index < 300 and pulmonary compliance < 30% of the baseline, the animals of heparin group received heparin infusion to maintain blood active coagulation time (ACT) 180 - 250 s, the animals of treatment group received CVVHDF with the blood flow of 50 ml/min, replacement rate of 300 ml/h, dialysis rate of 600 ml/h and the ultrafiltrate rate of 350 ml/h for six hours, heparin infusion to keep blood ACT 180 - 250 s. The circulatory parameters: heart rate (HR), mean arterial blood pressure (MABP), central venous pressure (CVP), pulse contour cardiac output index (PCCI); systemic venous resistance index (SVRI), cardiac function index (CFI), external venous lung water index (EVLWI), left ventricular contractile index (dPmx); respiratory parameters: respiratory rate (RR), pulmonary compliance (Cdyn) were monitored; arterial blood gas analysis was performed and oxygenation index (PaO2/FiO2) was calculated. All the parameters were recorded at baseline (B), onset of ALI (A 0 h), two hours (A 2 h), four hours (A 4 h), six hours (A 6 h) after ALI.

RESULTSNo significant difference in circulatory parameters, respiratory parameters and blood gas analysis were found at B and A 0 h among the three groups. When the ALI occurred, PaO2/FiO2, Cdyn, MABP and PCCI of the three groups decreased; HR, RR, EVLWI, SVRI increased. After four hours of ALI, the RR, EVLWI, SVRI, CFI and dPmx of treatment group were improved, the differences were significant compared with the other two groups (P < 0.05). After six hours of ALI, the HR, PCCI, MABP, PaO2/FiO2 and Cdyn of treatment group were significantly improved, compared with control group and heparin group (P < 0.05). There were no significant differences in any of the parameters between control group and heparin group. The difference in CVP among three groups was not significant.

CONCLUSIONCVVHDF has a good effect on hemodynamics of the endotoxin-induced ALI of the piglets.

Acute Lung Injury ; etiology ; physiopathology ; therapy ; Animals ; Endotoxins ; adverse effects ; Hemodiafiltration ; Hemodynamics ; Swine