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 study the protective effects of Ginkgo biloba extract (EGb) on the lung injury of dogs undergoing hypothermic cardiopulmonary bypass (CPB).

METHODSFourteen healthy hybrid dogs were randomly divided into the control group and the EGb group, 7 in each group. EGb (8 mg/kg) was intravenously dripped to dogs in the EGb group before thoracotomy after anesthesia, while equal volume of normal saline was intravenously dripped to those in the control group. The lung tissue was collected after 60-min CPB and 120-min recovery of heart beat. The lung tissues were collected to detect the wet weight-dry weight ratio and the permeability. The contents of malondialdehyde (MDA), the activities of myeloperoxidase (MPO) and total superoxide dismutase (T-SOD) in the lung tissues were detected by biochemical assay. The levels of IL-1beta, IL-8, tumor necrosis factor alpha (TNF-alpha), platelet activating factor (PAF) in the lung tissue were detected by enzyme linked immunosorbent assay (ELISA).

RESULTSCompared with the control group, the wet weight-dry weight ratio was reduced and the permeability of the lung tissue decreased (P < 0.05), the MDA content was reduced, the activity of MPO decreased, and the activity of T-SOD increased (P < 0.05), and the levels of IL-1beta, IL-8, and PAF obviously decreased (P < 0.05).

CONCLUSIONSEGb showed better protective effects on the lung injury of dogs undergoing hypothermic CPB. Its possible mechanisms might be associated with alleviating ischemia-reperfusion injury of in vitro circulation and systemic inflammatory response.

Animals ; Cardiopulmonary Bypass ; adverse effects ; methods ; Dogs ; Ginkgo biloba ; Lung Injury ; etiology ; prevention & control ; Plant Extracts ; pharmacology

With the increasing incidence of blast injury, the research on its mechanisms and protective measures draws more and more attention. Blast injury has many characteristics different from general war injuries or trauma. For example, soldiers often have various degrees of visceral injury without significant surface damage, combined injuries and arterial air embolism. Researchers in China began to investigate blast injury later than the United States and Sweden, but the development is so fast that lots of achievements have been gained, including the development of biological shock tube, the mechanisms and characteristics of blast injury in various organs, as well as protective measures under special environments. This article reviews the past and current situation of blast injury research in China.
Animals ; Blast Injuries ; diagnosis ; etiology ; prevention & control ; therapy ; Brain Injuries, Traumatic ; etiology ; China ; Disease Models, Animal ; Ear ; injuries ; Eye Injuries ; etiology ; High-Energy Shock Waves ; Humans ; Lung Injury ; etiology ; Research

AIMTo approach the relationship between lung injury induced by shock/reperfusion and nitric oxide as well as the beneficial effect of taurine.

METHODSTwenty four rabbits were divided randomly into 3 groups (n = 8): control group, shock group, taurine group. The model of lung injury induced by shock/reperfusion was used. The activities of nitric oxide synthase (NOS), superoxide dismutase (SOD), the contents of malondialdehyde (MDA), nitric oxide products (NO2-/NO3-) in plasma and lung homogenate, lung wet/dry weight, lung water content, lung permeability index, and protein content in the pulmonary alveolar lavage fluid were measured. Meanwhile, pathologic samples treated routinely.

RESULTS(1) At 3 hours after reperfusion, the activities of SOD in plasma and lung homogenate decreased markedly, but the other indexes above mentioned were increased significantly compared with the control group (P < 0.01). (2) A close correlation was shown between MDA content and NO2-/NO3- content in plasma and lung. Furthermore, the content of NO2-/NQ3- in lung homogenate showed strong positive correlation with the lung injury parameters. (3) Taurine (40 mg x kg(-1) i.v.) could attenuate all the changes above mentioned at the same time points of reperfusion.

CONCLUSIONNO may play an important role in lung injury induced by shock/reperfusion. Taurine can ameliorate the lung injury, mechanism of which may be related to decreasing the generation of NO and anti-lipoperoxidation.

Animals ; Lung ; drug effects ; metabolism ; Lung Injury ; etiology ; prevention & control ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rabbits ; Reperfusion Injury ; complications ; drug therapy ; Shock, Hemorrhagic ; complications ; drug therapy ; Superoxide Dismutase ; metabolism ; Taurine ; pharmacology ; therapeutic use

OBJECTIVETo investigate the effects of ulinastatin on lung injury in hemorrhagic shock rats.

METHODSTwenty-four normal SD rats were randomly divided into 3 groups (n=8), namely the control group, hemorrhagic shock group (group H) and ulinastatin group (group U). In group H and group U, blood was drawn from the femoral artery over a period of 10 min until a mean arterial pressure of 40 mmHg was obtained. Controlled hypotension was then maintained at 40-/+5 mmHg for 60 min by blood drawing or infusion when necessary. All the blood drawn and an equivalent volume of Ringer lactate solution were subsequently infused for resuscitation. Four hours after the resuscitation, the activity of superoxidedismutase (SOD), content of malondialdehyde (MDA), expression of heme oxygenase-1 (HO-1), wet to dry weight ratio (W/D), and pathologic changes of the lung tissues were measured or observed.

RESULTSCompared with those in the control group, the content of MDA, expression of HO-1 and W/D increased significantly in both group H and group U (P<0.05); these indexes in group U were significantly lower than those in group H (P<0.05). The activity of SOD in group U was significantly lower than that in the control group (P<0.05) but higher than that in group H (P<0.05). Optical microscopy demonstrated milder inflammatory cell infiltration and interstitial edema in the lung tissues in group U than in group H.

CONCLUSIONUlinastatin can lower the content of MDA, W/D and the expression of HO-1, increase the activity of SOD, and reduce histological lung injury in rats with hemorrhagic shock.

Animals ; Glycoproteins ; pharmacology ; Heme Oxygenase-1 ; metabolism ; Lung Injury ; etiology ; prevention & control ; Male ; Malondialdehyde ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic ; complications ; metabolism ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the effect of pentoxifylline on one-lung ventilation injury in rabbits.

METHODSTwenty rabbit models of one-lung ventilation by intrabronchial intubation after tracheotomy were randomly allocated in control group (with one-lung ventilation) and experiment group (with one-lung ventilation and intravenous pentoxifylline administration). One-lung ventilation was maintained for 3 h in both groups using the volume-control mode (tidal volume of 8 ml/kg at the frequency of 30 per min). Arterial blood samples were taken after anesthesia and at 3 h of one-lung ventilation for arterial blood gas analysis to obtain the oxygenation index. At the end of the experiment, the pulmonary wet/dry ratio (W/D), tumor necrosis factor-alpha (TNF-alpha), NO, malondialdehyde (MDA) and superoxide dismutase (SOD) contents in bronchoalveolar lavage fluid (BALF) were measured and the histological appearance of the lung tissue was observed.

RESULTSThe oxygenation index was significantly higher (P<0.05), W/D ratio lower (P<0.05), and contents of TNF-alpha, NO and MAD in the BALF lower in the experimental group than in the control group (P<0.05). The activity of SOD increased significantly in the experimental group as compared with the control group (P<0.01), and the rabbits in the experimental group showed milder pathological changes.

CONCLUSIONIntravenous pentoxifylline may improve pulmonary ventilation function and alleviate pulmonary injury, thus offering protection against pulmonary injury after one-lung ventilation.

Acute Lung Injury ; etiology ; prevention & control ; Animals ; Continuous Positive Airway Pressure ; methods ; Female ; Intubation, Intratracheal ; Male ; Pentoxifylline ; pharmacology ; Pulmonary Ventilation ; Rabbits ; Respiration, Artificial ; adverse effects ; methods

OBJECTIVETo investigate the protective effect of exogenous inhibitor of matrix metalloproteinases-9 (MMP-9), batimastat, in the lung injury induced by cardiopulmonary bypass (CPB) in dogs.

METHODSThirty healthy mongrel puppies were randomly divided into 3 groups: control group, low-dose group [batimastat 10 mg/(kg.d) for 3 days before operation] and high-dose group [batimastat 30 mg/(kg.d) for 3 days before operation]. The off-pump puppies' model of acute lung injury was established, and hemodynamic and respiratory parameters were monitored. The preoperative and postoperative alveolar-arterial oxygen difference (A-aDO(2)) and respiratory index (RI) were calculated. From the beginning of surgery, blood samples were taken at the time 0, 60, 120, and 270 min. Plasma concentrations of MMP-9 were measured by ELISA, and blood MMP-9 mRNA expressions were determined by RT-PCR. The myeloperoxidase (MPO) activity of centrifugal bronchoalveolar lavage fluid were measured by Colorimetry. And MMP-9 activity was determined by Gelatin zymography. Light and electronic microscope were used to observe the morphological changes of lung tissue. A small piece of left lung tissue was taken, weighed and baked to calculate the wet weight (W/D) index.

RESULTSAfter cardiopulmonary bypass, the concentrations of MMP-9 and mRNA expressions of the control group were increased significantly, and lung injury was apparent. At 270 min, the MMP-9 plasma concentration of high-dose group (17.36 +/- 1.18) microg/L was significant reducing than control group (30.47 +/- 2.22) microg/L (P < 0.05). After operation, A-aDO(2) and RI of high-dose group were significantly improved than control group (P < 0.05). The W/D index of the high-dose group (2.8 +/- 0.48) was significantly lower than that of control group (4.7 +/- 0.6) (P < 0.05). And the pathological changes of lung tissue were significantly improved in the high-dose group. However, there was no significant difference in the MMP-9 mRNA expression in three groups.

CONCLUSIONSBatimastat plays a role in the protection of the lung injury of CBP by reducing the concentration and activity of MMP-9, the degradation of the cell membrane and pulmonary neutrophil infiltration and reduction of pulmonary edema.

Acute Lung Injury ; etiology ; prevention & control ; Animals ; Cardiopulmonary Bypass ; Disease Models, Animal ; Dogs ; Lung ; pathology ; Matrix Metalloproteinase 9 ; metabolism ; Matrix Metalloproteinase Inhibitors ; Phenylalanine ; analogs & derivatives ; pharmacology ; Postoperative Complications ; prevention & control ; Thiophenes ; pharmacology

OBJECTIVETo investigate the effect of H₂S on lower limb ischemia-reperfusion (LIR) induced lung injury and explore the underlying mechanism.

METHODSWistar rats were randomly divided into control group, IR group, IR+ Sodium Hydrosulphide (NaHS) group and IR+ DL-propargylglycine (PPG) group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NaHS (0.78 mg/kg) as exogenous H₂S donor and PPG (60 mg/kg) which can suppress endogenous H₂S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1 (AQP₁), aquaporin-5 (AQP₅) as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4 (TLR₄), myeloid differentiation primary-response gene 88 (MyD88) and p-NF-κB as indexes of inflammation.

RESULTSLIR induced lung injury was accompanied with upregulation of TLR₄-Myd88-NF-κB pathway and downregulation of AQP1/AQP₅. NaHS pre-treatment reduced lung injury with increasing AQP₁/AQP₅ expression and inhibition of TLR₄-Myd88-NF-κB pathway, but PPG adjusted AQP₁/AQP₅ and TLR4 pathway to the opposite side and exacerbated lung injury.

CONCLUSIONEndogenous H₂S, TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ were involved in LIR induced lung injury. Increased H₂S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ expression to reduce inflammatory reaction and lessen pulmonary edema.

Acute Lung Injury ; complications ; pathology ; prevention & control ; Animals ; Aquaporins ; metabolism ; Drug Evaluation, Preclinical ; Edema ; etiology ; pathology ; Hydrogen Sulfide ; pharmacology ; therapeutic use ; Inflammation ; prevention & control ; Lung ; pathology ; Male ; Myeloid Differentiation Factor 88 ; metabolism ; NF-kappa B ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; complications ; pathology ; prevention & control ; Toll-Like Receptor 4 ; metabolism ; Water ; metabolism

OBJECTIVETo investigate the protective effects of captopril against lung injury in a rat model of severe acute pancreatitis (SAP).

METHODSSeventy-two male SD rats were randomized into sham-operated group (SO group), SAP group and captopril intervention group (CAP group). Serum amylase and myeloperoxidase (MPO) activity in the lung tissue were examined at 1, 6 and 12 h after the operation. TNF-α and AngII in the lung tissue were detected by ELISA, and the histopathological changes of the pancreas and lung were observed microscopically.

RESULTSThe MPO activity , which was similar between SAP group and CAP group at 1 h, were significantly lowered in CAP group at 6 and 12 h (P<0.05). Serum amylase level and the levels of TNF-α and AngII in the lung tissue homogenate were all reduced significantly in CAP group as compared to those in SAP group (P<0.01). The pathological injury of the lung was obviously lessened in CAP group in comparison with that in SAP group.

CONCLUSIONCaptopril can ameliorate SAP-induced lung injury in rats.

Amylases ; blood ; Angiotensin II ; metabolism ; Animals ; Captopril ; pharmacology ; therapeutic use ; Disease Models, Animal ; Lung ; metabolism ; pathology ; Lung Injury ; etiology ; prevention & control ; Male ; Pancreatitis ; complications ; drug therapy ; Peroxidase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVE: To assess the effect of neutralizing CD96 on natural killer (NK) cell functions in mice with pulmonary infection and explore the possible mechanism. METHODS: Male BALB/c mice were randomly divided into infection group (Cm group), anti-CD96 treatment group (anti-CD96 group) and control group (=5). In the former two groups, was inoculated intranasal administration to establish mouse models of pulmonary infection, and the mice in the control group received intranasal administration of the inhalation buffer. In anti-CD96 group, the mice were injected with anti-CD96 antibody intraperitoneally at the dose of 250 μg every 3 days after the infection; the mice in Cm group received intraperitoneal injections of saline. The body weight of the mice was recorded daily. The mice were sacrificed 5 days after infection, and CD96 expression was detected by quantitative real-time PCR and Western blotting. HE staining and pathological scores were used to evaluate pneumonia of the mice. The inclusion body forming units (IFUs) were detected in the lung tissue homogenates to assess lung tissue chlamydia load. Flow cytometry and ELISA were used to assess the capacity of the lung NK cells to produce interferon-γ (IFN-γ) and regulate macrophages and Th1 cells. RESULTS: infection inhibited CD96 expression in NK cells of the mice. Compared with those in Cm group, the mice in antiCD96 mice showed significantly milder lung inflammation ( < 0.05) and reduced chlamydia load in the lung tissue ( < 0.05). Neutralizing CD96 with anti-CD96 significantly enhanced IFN-γ secretion by the NK cells ( < 0.05) and augmented the immunoregulatory effect of the NK cells shown by enhanced responses of the lung macrophages ( < 0.05) and Th1 cells ( < 0.05). CONCLUSIONS Inhibition of CD96 alleviates pneumonia in -infected mice possibly by enhancing IFN-γ secretion by NK cells and augmenting the immunoregulatory effect of the NK cells on innate and adaptive immunity.
Animals ; Antigens, CD ; metabolism ; Chlamydia Infections ; complications ; immunology ; physiopathology ; Chlamydia muridarum ; Interferon-gamma ; genetics ; metabolism ; Killer Cells, Natural ; metabolism ; Lung Injury ; etiology ; genetics ; prevention & control ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL