Associations of high-mobility group box 1 and receptor for advanced glycation end products with acute lung injury in patient with acute aortic dissection

SUMMARY OBJECTIVE: To investigate the associations of high-mobility group box 1 and its specific receptor, receptor for advanced glycation end products with acute lung injury in patients with acute aortic dissection. METHODS: A total of 96 acute aortic dissection patients were divided into acute aortic dissection with acute lung injury group (38 cases) and acute aortic dissection without acute lung injury group (58 cases), according to partial pressure of oxygen/fraction of inspired oxygen. In addition, 44 healthy individuals were selected for the control group. The blood samples were taken. The serum high-mobility group box 1 and receptor for advanced glycation end products levels were detected by enzyme-linked immunosorbent assay, and the partial pressure of oxygen/fraction of inspired oxygen was measured. RESULTS: 24 h after admission, the high-mobility group box 1 and receptor for advanced glycation end products levels in acute aortic dissection with acute lung injury and acute aortic dissection without acute lung injury groups were significantly higher than those in the control group, respectively (p<0.05), and each index in acute aortic dissection with acute lung injury group was significantly higher than that in acute aortic dissection without acute lung injury group (p<0.05). At each time point within 96 h after admission, compared with acute aortic dissection without acute lung injury group, in acute aortic dissection with acute lung injury group, the high-mobility group box 1 and receptor for advanced glycation end products levels were increased, respectively, and the partial pressure of oxygen/fraction of inspired oxygen was decreased. The correlation analysis showed that, in acute aortic dissection patients, the high-mobility group box 1 and receptor for advanced glycation end products levels were negatively correlated with partial pressure of oxygen/fraction of inspired oxygen, respectively (p<0.05). CONCLUSIONS: The serum high-mobility group box 1 and receptor for advanced glycation end products levels may be associated with the occurrence of acute lung injury in acute aortic dissection patients. Monitoring the high-mobility group box 1 and receptor for advanced glycation end products levels can evaluate the risk of acute aortic dissection with acute lung injury.

Melatonin can be, more effective than N-acetylcysteine, protecting acute lung injury induced by intestinal ischemia-reperfusion in rat model

OBJECTIVES: The current study compared the impact of pretreatment with melatonin and N-acetylcysteine (NAC) on the prevention of rat lung damage following intestinal ischemia-reperfusion (iIR). METHODS: Twenty-eight Wistar rats were subjected to intestinal ischemia induced by a 60 min occlusion of the superior mesenteric artery, followed by reperfusion for 120 min. Animals were divided into the following groups (n=7 per group): sham, only abdominal incision; SS+iIR, pretreated with saline solution and iIR; NAC+iIR, pretreated with NAC (20 mg/kg) and iIR; MEL+iIR, pretreated with melatonin (20 mg/kg) and iIR. Oxidative stress and inflammatory mediators were measured and histological analyses were performed in the lung tissues. RESULTS: Data showed a reduction in malondialdehyde (MDA), myeloperoxidase (MPO), and TNF-alpha in the animals pretreated with NAC or MEL when compared to those treated with SS+iIR (p<0.05). An increase in superoxide dismutase (SOD) levels in the NAC- and MEL-pretreated animals as compared to the SS+iIR group (34±8 U/g of tissue; p<0.05) was also observed. TNF-α levels were lower in the MEL+iIR group (91±5 pg/mL) than in the NAC+iIR group (101±6 pg/mL). Histological analysis demonstrated a higher lung lesion score in the SS+iIR group than in the pretreated groups. CONCLUSION: Both agents individually provided tissue protective effect against intestinal IR-induced lung injury, but melatonin was more effective in ameliorating the parameters analyzed in this study.

Glycogen synthase kinase-3 beta inhibitors protectagainst the acute lung injuries resulting from acute necrotizing pancreatitis

Abstract Purpose The research is intended for clarification of the efficacy as well as the underlying mechanism of GSK-3β inhibitors on the advancement of acute lung injuries in acute necrotizing pancreatitis (ANP) in rats. Methods Seventy-two rats were randomly divided into 6 groups: (1)ANP-vehicle; (2)ANP-TDZD-8;(3)ANP-SB216763;(4)Sham-vehicle;(5)Sham-TDZD-8;(6)Sham-SB216763; Blood biochemical test, histopathological examination and immunohistochemical analysis of rats pancreas and lung tissues were performed. The protein expression of GSK-3β, phospho-GSK-3β (Ser9), iNOS, ICAM-1, TNF-α, and IL-10 were detected in lung tissues by Western-blot. Results The outcomes revealed that the intervention of GSK-3β inhibitors alleviated the pathological damage of pancreas and lung (P<0.01), reduced serum amylase, lipase, hydrothorax and lung Wet-to-Dry Ratio, attenuated serum concentrations of IL-1β and IL-6 (P<0.01), inhibited the activation of NF-κB, and abated expression of iNOS, ICAM-1 and TNF-α protein, but up-regulated IL-10 expression in lung of ANP rats (P<0.01). The inflammatory response and various indicators in ANP-TDZD-8 groups were lower than those in ANP-SB216763 groups. Conclusions Inhibition of GSK-3β weakens acute lung injury related to ANP via the inhibitory function of NF-κB signaling pathway. Different kinds of GSK-3β inhibitors have different effects to ANP acute lung injury.

Analysis of risk factors for acute lung injury/acute respiratory distress syndrome after esophagectomy / 北京大学学报(医学版)

OBJECTIVE@#To explore the incidence and risk factors for the acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) after resection of esophageal carcinoma.@*METHODS@#We retrospectively analyzed 422 consecutive patients admitted to the Department of Critical Care Medicine with esophageal carcinoma undergoing esophagectomy from January 2010 to December 2016 in Peking University Cancer Hospital. ALI/ARDS were diagnosed, the patients were divided into ALI/ARDS group and control group without ALI/ARDS, the differences of clinical features were contrasted between the two groups, and the multivariate Logistic regression modeling was used to identify the independent risk factors for ALI/ARDS.@*RESULTS@#In the study, 41 ALI/ARDS cases were diagnosed, making up 9.7% (41/422) of all the enrolled patients undergoing esophagectomy. Comparisons of the ALI/ARDS group and the control group indicated significant statistical differences in the average length of their hospital stay [(18.9±9.7) d vs. (14.8±3.6) d, P=0.011], the proportion of the patients who needed mechanical ventilation support [51.2% (21/41) vs. 9.4% (36/381), P<0.001] and in-hospital mortality [31.7% (13/41) vs. 5.0% (19/381), P<0.001]. Univariate analysis showed significant differences between the patients with ALI/ARDS and without ALI/ARDS in smoking history (P=0.064), preoperative forced expiratory volume in one second/forced vital capacity (FEV1/FVC) (P=0.020), diffusing capacity of the lung for carbon monoxide (DLCO) (P=0.011), body weight index (BMI) (P=0.044), American Society of Anesthesiologists (ASA) physical status classification (P=0.049) and one lung ventilation duration (P=0.008), while multivariate Logistic regression analysis indicated that preoperative FEV1/FVC (OR=1.053, P=0.016, 95%CI 1.010-1.098), ASA physical status classification (OR=2.392, P=0.033, 95%CI 1.073-5.335) and one lung ventilation duration (OR=0.994, P=0.028, 95%CI 0.989-0.999) were the independent risk factors for ALI/ARDS after esophagectomy.@*CONCLUSION@#ALI/ARDS was a serious complication in patients undergoing esophagectomy associated with increment in length of hospital stay and in-hospital mortality. Multivariate Logistic regression analysis indicated that preoperative FEV1/FVC, ASA classification and one lung ventilation duration were the independent risk factors for ALI/ARDS after esophagectomy. Carefully assessing the patient before operation, shortening one lung ventilation duration were the key points in preventing ALI/ARDS after esophagectomy.

Effects of CpG oligodeoxynucleotide 1826 on acute radiation-induced lung injury in mice

BACKGROUND: The radiation-induced lung injury is a common complication from radiotherapy in lung cancer. CpG ODN is TLR9 activator with potential immune modulatory effects and sensitization of radiotherapy in lung cancer. This study aimed to examine the effect of CpG ODN on acute radiation-induced lung injury in mice. METHODS AND RESULTS: The mouse model of radiation-induced lung injury was established by a single dose of 20 Gy X-rays exposure to the left lung. The results showed that the pneumonia score was lower in RT+CpG group than in RT group on 15th and 30th days. Compared with RT group, CpG ODN reduced the serum concentrations of MDA (P < 0.05) and increased the serum concentrations of SOD, GSH (P < 0.05). The serum concentration of TNF-α in RT+CpG group was lower on 15th and 30th days post-irradiation (P < 0.05). CONCLUSION: The study demonstrated that CpG ODN has preventive effects of acute radiation-induced lung injury in mice. Lung inflammatory reaction and oxidative stress are promoted in the initiation of radiation-induced pneumonia. CpG ODN may reduce the injury of reactive oxygen species and adjust the serum TNF-α concentration in the mice after irradiation, which reduces the generation of the inflammatory cytokines.

Possible Transfusion-Related Acute Lung Injury Following Convalescent Plasma Transfusion in a Patient With Middle East Respiratory Syndrome

No abstract available.

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.

Therapeutic effects of compound hypertonic saline on rats with sepsis

Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran) after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis.

The Role of Platelets in Malarial Acute Lung Injury and Acute Respiratory Distress Syndrome: A World of Possibilities.

In recent decades our understanding of platelets’ role in immune response has increased. Traditionally platelets were considered as bleeding-stopping and thrombosis-causing cells. In recent years the platelets’ role in malarial innate and adaptive immune responses is being recognized. Platelets play critical role in pathogenesis of malaria infection leading to variety of outcomes. It is being realized that platelets play dual role in case of malaria (i) by preventing early stage exponential growth of parasitemia (ii) promoting exaggerated immune responses later. Platelets role in pathogenesis of severe and cerebral malaria has been widely studied. However their role in malaria related acute lung injury and respiratory distress has gained less attention. Recently the presence of active megakaryocytes and proplatelets have been explained in human lungs. Simultaneously, the platelets role in pathogenesis of acute lung injury and respiratory distress (ALI/ARDS) was also recognized. This gives a hint that there is a possible association of platelets with malaria related respiratory diseases as well. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. In this review we have attempted to establish the importance of role of platelets in malaria related acute lungs injury and malaria acute respiratory distress syndrome and try to explain the underlying mechanism of this process. In ALI/ARDS, including those caused by malaria, platelets participate sequestration to the vascular bundle facilitating the recruitment of immune cells viz. neutrophils. Additionally, they secrete or induce the secretion of chemokines that result into vascular damage.

Coagulopathy as a Prognostic Factor of Acute Lung Injury in Children

The coagulation cascade and inflammatory process are known to be associated with the pathophysiology of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We retrospectively investigated laboratory values indicating coagulopathy obtained within 24 hr from diagnosis of ALI/ARDS in 79 children who received mechanical ventilation between 2008 and 2009 and their final outcomes. Prothrombin time (PT) (P = 0.001) and activated partial thromboplastin time PTT (APTT) (P = 0.001) were more prolonged in non-survivors than survivors (mean; 1.57 vs 1.33; 63 vs 57). In multivariate analysis with stratification by oxygenation-index ( or = 14.5), prolonged PT (> or = 1.46 international normalized ratio, [INR]) (hazard ratio; 2.043, 1.027-4.064) was associated with lower non-pulmonary-organ-failure-free survival rate (FFS), and prolonged APTT (> or = 50 seconds) (2.062, 1.031-4.121; 2.422, 1.227-4.781) was associated with lower overall survival rate (OS) and lower FFS. In stratification by ventilation-index ( or = 40), prolonged PT (2.232, 1.095-4.540; 2.177, 1.092-4.342) and prolonged APTT (2.574, 1.230-5.386; 3.089, 1.500-6.360) were associated with lower OS and lower FFS. Prolonged PT and APTT are associated with mortality in mechanically ventilated children with ALI/ARDS. We suggest PT and APTT as prognostic factors of ALI/ARDS in children.

Acute pulmonary injury induced by experimental muscle trauma / Lesão pulmonar aguda induzida por trauma muscular experimental

PURPOSE: To develop an easily reproducible model of acute lung injury due to experimental muscle trauma in healthy rats. METHODS: Eighteen adult Wistar rats were randomized in 3 groups (n=6): G-1- control, G-2 - saline+trauma and G-3 - dexamethasone+trauma. Groups G-1 and G-2 were treated with saline 2,0ml i.p; G-3 rats were treated with dexamethasone (DE) (2 mg/kg body weight i.p.). Saline and DE were applied 2h before trauma and 12h later. Trauma was induced in G-2 and G-3 anesthetized (tribromoethanol 97 percent 100 ml/kg i.p.) rats by sharp section of anterior thigh muscles just above the knee, preserving major vessels and nerves. Tissue samples (lung) were collected for myeloperoxidase (MPO) assay and histopathological evaluation. RESULTS: Twenty-four hours after muscle injury there was a significant increase in lung neutrophil infiltration, myeloperoxidase activity and edema, all reversed by dexamethasone in G-3. CONCLUSION: Trauma by severance of thigh muscles in healthy rats is a simple and efficient model to induce distant lung lesions.

OBJETIVO: Desenvolver um modelo facilmente reprodutível de lesão pulmonar aguda decorrente de trauma muscular experimental em ratos sadios. MÉTODOS: Dezoito ratos Wistar adultos foram randomizados em 3 grupos (n=6): G-1-controle, G-2 - trauma+salina e G-3 - trauma+dexametasona. Grupos G-1 e G-2 foram tratados com salina 2,0 ml ip, G-3 ratos foram tratados com dexametasona (DE) (2 mg/kg peso corporal ip). Salina e DE foram aplicadas 2h antes e 12h depois do trauma. Trauma foi induzido em ratos G-2 e G-3 anestesiados (tribromoetanol 97 por cento de 100 ml/kg, i.p.) por secção da musculatura anterior da coxa logo acima da articulação do joelho, preservando os grandes vasos e nervos. Amostras de tecido (pulmão) foram coletadas para avaliação da mieloperoxidase (MPO), e exames histopatológicos. RESULTADOS: Vinte e quatro horas após a indução da lesão muscular houve um aumento significativo na infiltração de neutrófilos pulmonares, atividade da mieloperoxidase e edema, todos revertidos por dexametasona, no G-3. CONCLUSÃO: O trauma decorrente da secção dos músculos da coxa em ratos saudáveis é um modelo simples e eficaz para induzir lesões pulmonares à distância.

The Role of Keratinocyte-derived Chemokine in Hemorrhage-induced Acute Lung Injury in Mice

Dominant inflammatory cytokines might be different depending on the underlying causes of acute lung injury (ALI). The role of kertinocyte-derived chemokine (KC), a potent chemoattractant for neutrophils, has not been clearly established in hemorrhage-induced ALI. In this study, lung injury and cytokine expressison were evaluated in LPS- or hemorrhage-induced ALI models of BALB/c mice. The myeloperoxidase activities at 4 hr after hemorrhage and LPS-injection were 47.4+/-13.0 and 56.5+/-16.4 U/g, respectively. NF-kappa B activity peaked at 4 hr after hemorrhage, which was suppressed to the control level by anti-high mobility group B1 (HMGB1) antibody. Lung expressions of TNF-alpha, MIP-2, and IL-1beta were increased by LPS injection. However, there was only a minimal increase in IL-1beta and no expressions of TNF-alpha or MIP-2 in hemorrhage-induced ALI. In contrast, lung KC increased significantly at 4 hr after hemorrhage compared to control levels (83.1+/-12.3 vs. 14.2+/-1.6 pg/mL/mg by ELISA) (P<0.05). By immunohistochemical staining, lung neutrophils stained positive for KC. Increased KC was also observed in bronchoalveolar lavage fluid and plasma. KC plays an important role in hemorrhage-induced ALI.