Neutrophils play a critical role in ventilation-induced lung injury. This study was aimed to investigate the characteristics of neutrophils influx in lungs induced by high tidal volume ventilation. Anaesthetized rats were randomly divided into low tidal volume ventilation group (Vt: 7 mL/kg, LV group) or high tidal volume ventilation group (Vt: 42 mL/kg, HV group) (n=40 in each). Rats in each group were ventilated for 0, 60, 90, 120 and 240 min. The wet/dry lung weight ratio (W/D) was measured. The levels of macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α), and the activity of myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay (ELISA). The number of neutrophils in bronchoalveolar lavage fluid (BALF) was counted after Wright's staining, and the percentage of netrophils in lung tissues calculated. Histopatholgical examination was used to observe the changes of lung tissues after different ventilations. The results showed that the W/D weight ratio was increased, and the levels of MIP-2 and TNF-α significantly enhanced in HV group at 90, 120 and 240 min. Neutrophils in BALF and the neutrophil percentage in lung tissues were also elevated at 120 and 240 min, which coincided with the enhanced activity of MPO in HV group. The lung injury was significantly related with the ventilation time and the infiltration of neutrophils in lungs in HV group. In conclusion, in ventilation-induced lung injury, neutrophil infiltration is present in a time-dependent manner and associated with the aggravated lung injury. Pulmonary structural damage may be the main reason for ventilation-induced lung injury.
Animals ; Lung ; physiopathology ; Lung Injury ; physiopathology ; Male ; Neutrophil Infiltration ; physiology ; Neutrophils ; physiology ; Rats ; Rats, Sprague-Dawley

Animals ; Blood Gas Analysis ; Brain Ischemia ; complications ; metabolism ; physiopathology ; Lung Injury ; etiology ; metabolism ; physiopathology ; Male ; Pyrazines ; pharmacology ; Rats ; Rats, Wistar ; Reperfusion Injury ; complications ; metabolism ; physiopathology

OBJECTIVETo explore the relationship between ulcerative colitis (UC) and lung injuries by assessing their clinical manifestations and characteristics.

METHODSFrom July 2009 to April 2012, 91 UC patients presenting to Longhua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study. According to the scores of disease activity index, the patients were divided into the mild, moderate, and severe groups. Meanwhile, the records of pulmonary symptoms, chest X-ray image, and pulmonary function were reviewed.

RESULTSSixty-eight (74.7%) patients had at least 1 pulmonary symptom, such as cough (38.5%), shortness of breath (27.5%), and expectoration (17.6%). And 77 (84.6%) had at least 1 ventilation abnormality. Vital capacity value was significantly lower in the severe group than that in the mild group (91.82%±10.38% vs. 98.92%±12.12%, P<0.05).

CONCLUSIONSLung injury is a common extraintestinal complication of UC. According to the theory in Traditional Chinese Medicine that the lung and large intestine are related, both the lungs and large intestine should be treated simultaneously.

Adult ; Colitis, Ulcerative ; complications ; physiopathology ; Female ; Humans ; Lung Injury ; etiology ; Male ; Middle Aged ; Vital Capacity

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

Radiation-induced lung injury (RILI), including acute radiation pneumonitis and chronic radiation-induced pulmonary fibrosis (RIPF), is a side effect of radiotherapy for lung cancer and esophageal cancer. Pulmonary macrophages, as a kind of natural immune cells maintaining lung homeostasis, play a key role in the whole pathological process of RILI. In the early stage of RILI, classically activated M1 macrophages secrete proinflammatory cytokines to induce inflammation and produce massive reactive oxygen species (ROS) through ROS-induced cascade to further impair lung tissue. In the later stage of RILI, alternatively activated M2 macrophages secrete profibrotic cytokines to promote the development of RIPF. The roles of macrophage in the pathogenesis of RILI and the related potential clinical applications are summarized in this review.
Humans ; Lung/radiation effects* ; Lung Injury/physiopathology* ; Macrophages/metabolism* ; Radiation Injuries ; Radiation Pneumonitis/etiology* ; Radiotherapy/adverse effects*

AIMTo study the effect of ischemic preconditioning on lung injury following ischemia/reperfusion (I/R) in the hind limbs of rats.

METHODSWistar rats were randomly divided into four groups (n=8): control group,limbs ischemia/reperfusion (LI/R) group, ischemia preconditioning (IPC) group and L-NAME group. At the end of the experiment, blood/gas analysis and the contents of serum MDA, NO, ET and lung tissue MDA, NO, ET, MPO were measured. Meanwhile, lung index and W/D) of lung were measured.

RESULTSAfter the rats' hind limbs suffered ischemia/reperfusion, the level of PaO2 decreased and the values of W/D, LI, MPO of the lung issure and MDA, NO, ET of plasma and lung all increased significantly in the LI/R group; but the ratio of NO/ET decreased. Compared with LI/R group, the contents of NO and ratio of NO/ET increased but other parameters decreased in the IPC group. Compared with IPC group, the contents of NO and ratio of NO/ET decreased, but other parameters increased in the L-NAME group.

CONCLUSIONThe IPC can attenuate lung injury following IR in the hind limbs of rats, which may correlated with the increase of NO.

Acute Lung Injury ; prevention & control ; Animals ; Extremities ; blood supply ; Ischemia ; physiopathology ; Ischemic Preconditioning ; methods ; Lung ; blood supply ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; prevention & control

OBJECTIVETo study the effect of oxygen at lethal levels (95%) on pulmonary development and lung injury in neonatal rats and establish rat models of bronchopulmonary dysplasia.

METHODSThree-day-old and adult SD rats were assigned to experimental or control groups and subjected to 95% O(2) exposure and room air for 7 days. Body weight and length of the rats were recorded, and histological study of the lung tissue and radical alveoli count (RAC) were carried out.

RESULTSThe mortality rate of the neonatal and adult rats was 12.5% and 35.2% in hyperoxia group, respectively. The newborn rats in hyperoxic group had lower body weight (18.02-/+0.68 vs 13.24-/+0.59 g) and length (8.83-/+0.25 vs 6.76-/+0.51 cm) than those in the control group (P<0.05), with also lower RAC (9.50-/+1.05 vs 13.00-/+1.79, P<0.05); RAC of the adult rats with hyperoxic exposure (12.67-/+2.25) was higher that of exposed neonatal rats, but not significantly different from that of the adult or neonatal rats in the control group (P>0.05). Structure configuration of the rats on the first 10 days of life resembled that of adulthood. The lung of hyperoxic neonatal rats showed thinner walls of alveoli, simple alveolar structure, fewer and larger alveoli, expanded and shrunk alveoli, while the lung of the adult rats displayed thicker septa, smaller space of alveoli, and cells in the space of the alveoli.

CONCLUSIONExposure of neonatal rats to 95% O(2) may result in mild pulmonary inflammation in addition to growth impediment and impaired lung development, which shares morphologic similarities to human bronchopulmonary dysplasia.

Animals ; Animals, Newborn ; Disease Models, Animal ; Female ; Hyperoxia ; complications ; physiopathology ; Lung ; physiopathology ; Lung Diseases ; etiology ; physiopathology ; Lung Injury ; Pregnancy ; Pulmonary Alveoli ; pathology ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which manifests as non-cardiogenic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.
Acute Disease ; Animals ; Cell Transplantation ; Genetic Therapy ; Humans ; Lung ; physiopathology ; Lung Injury ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; etiology ; physiopathology ; therapy

OBJECTIVETo investigate the protective effect of ulinastatin (UTI) against acute lung injury induced by heatstroke in mice.

METHODSSixty C57/BL6 mice were randomly divided into 6 groups, with 10 mice in each: control group, heatstroke group, UTI pretreatment group, saline pretreatment group, UTI post-treatment group, saline post-treatment group. The control mice were housed at a controlled room temperature of (22∓1) degrees; celsius, and the other groups were placed inside a temperature and humidity controlled chamber pre-set at 37 degrees; celsius and 60%. The two UTI groups were intraperitoneally injected with UTI at 5×10(4) U/kg 10 min before or after heat stress, and the two saline groups were given then equal amounts of saline in the same manner. The core body temperature of mice was monitored by a mercury thermometer every 30 min in the first 1.5 h during heating. The core temperature was measured, then every 15 min until it reached 42.7 degrees; celsius, which was taken as the onset of heatstroke. The animals were allowed to recover passively at ambient temperature for 6 h. The lung histopathological changes, protein concentration in BALF, lung wet/dry weight ratios, lung water content, and pulmonary microvascular permeability were assayed after 6 h of recovery at 37 degrees;celsius.

RESULTSCompared with the control group, the heatstroke model group and two saline groups displayed more severe lung damage and pathological morphology changes, and the lung wet/dry weight ratio, protein concentration in BALF, lung water content and pulmonary microvascular permeability were also significantly increased. These effects were significantly alleviated in UTI treated group. Pretreat ment with UTI significantly prolonged the time to Tc≥42.7 degrees; celsius but had no effect on lung injury induced by heatstroke.

CONCLUSIONUTI can reduce the pulmonary edema and inflammatory exudation in acute lung injury caused by heatstroke.

Acute Lung Injury ; drug therapy ; physiopathology ; Animals ; Body Temperature ; Bronchoalveolar Lavage Fluid ; chemistry ; Edema ; prevention & control ; Glycoproteins ; therapeutic use ; Heat Stroke ; physiopathology ; Lung ; pathology ; Mice ; Mice, Inbred C57BL

BACKGROUNDAnimal models that demonstrate changes of renal function in response to acute lung injury (ALI) and mechanical ventilation (MV) are few. The present study was performed to examine the effect of ALI induced by oleic acid (OA) in combination with conventional MV strategy on renal function in piglets.

METHODSTwelve Chinese mini-piglets were randomly divided into two groups: the OA group (n = 6), animals were ventilated with a conventional MV strategy of 12 ml/kg and suffered an ALI induced by administration of OA, and the control group (n = 6), animals were ventilated with a protective MV strategy of 6 ml/kg and received the same amount of sterile saline.

RESULTSSix hours after OA injection a severe lung injury and a mild-moderate degree of renal histopathological injury were seen, while no apparent histological abnormalities were observed in the control group. Although we observed an increase in the plasma concentrations of creatinine and urea after ALI, there was no significant difference compared with the control group. Plasma concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C increased (5.6 ± 1.3) and (7.4 ± 1.5) times in the OA group compared to baseline values, and were significantly higher than the values in the control group. OA injection in combination with conventional MV strategy resulted in a dramatic aggravation of hemodynamic and blood gas exchange parameters, while these parameters remained stable during the experiment in the control group. The plasma expression of TNF-α and IL-6 in the OA group were significantly higher than that in the control group. Compared with high expression in the lung and renal tissue in the OA group, TNF-α and IL-6 were too low to be detected in the lung and renal tissue in the control group.

CONCLUSIONSOA injection in combination with conventional MV strategy not only resulted in a severe lung injury but also an apparent renal injury. The potential mechanisms involved a cytokine response of TNF-α and IL-6 in plasma, lung and renal tissues.

Acute Lung Injury ; chemically induced ; pathology ; physiopathology ; Animals ; Cytokines ; analysis ; Hemodynamics ; Kidney ; pathology ; physiopathology ; Lung ; pathology ; Oleic Acid ; pharmacology ; Respiration, Artificial ; Swine ; Swine, Miniature