[Effects of ventilation in prone position combined with recruitment maneuver on lung injury in dogs with acute respiratory distress syndrome].

OBJECTIVE: To evaluate protective effect and its mechanism of prone position ventilation (PPV) combined with recruitment maneuver (RM) as a lung protective ventilation strategy on oleic acid-induced acute respiratory distress syndrome (ARDS) in dogs. METHODS: Twenty-four oleic acid-induced ARDS dogs were ventilated with volume controlled ventilation (VCV): 16 cm H2O (1 cm H2O=0.098 kPa) of positive end-expiratory pressure (PEEP) and 10 ml/kg of tidal volume (VT). All dogs were randomly divided by random digit table into four groups: supine position (SP group), prone position (PP group), supine position+RM (SPRM group), and prone position+RM (PPRM group, 6 in each group), and ventilated by VCV for 4 hours and then sacrificed by exsanguination. The serum levels of inflammatory mediators were measured respectively at 0.5, 2 and 4 hours. After they were sacrificed, the levels of cytokines in left lung tissue homogenate were measured. The wet/dry weight ratio of right lung was determined and histological sections of the lungs were prepared and examined. RESULTS: (1) At 4 hours, interleukin-8 (IL-8) in serum in the SPRM group was significantly higher than in other three groups (all P<0.05), tumor necrosis factor-alpha (TNF-alpha) in serum in the SPRM group was significantly higher than in the PP group and the PPRM group (all P<0.05). (2) IL-8 in lung tissue homogenate of the dorsal aspect of the lung in the SP group was higher than in the PP group and the PPRM group (both P<0.05). TNF-alpha in lung tissue homogenate at the dorsal aspect of the lung in the SPRM group was higher than in the PP group and the PPRM group (both P<0.05). (3) Wet/dry weight ratio of right lung in the PP group and the PPRM group were significantly lower than that in the SP group and the SPRM group (all P<0.05). (4)Pathology score of lung tissue at the dorsal aspect of the lung in the PP group and PPRM group was significantly lower than in the SP group and the SPRM group (all P<0.05). CONCLUSION: Protective ventilation strategy combined with RM is safer in prone position than supine position, and it alleviates lung injury in dog with ARDS.

[Nitric oxide inhalation improves alveolar liquid clearance in rabbit with endotoxin induced acute lung injury].

OBJECTIVE: To investigate the effects of nitric oxide (NO) inhalation (iNO) on alveolar liquid clearance (ALC), alveolar permeability, and lung edema, and its possible mechanism. METHODS: Eighteen male rabbits were challenged with endotoxin, and they were randomly assigned into three groups: mechanical ventilator (MV) group [volume control ventilation: tidal volume (V(T)) 15 ml/kg, respiration rate (RR) 40 beats/minute, positive end-expiratory pressure (PEEP): 5 cm H(2)O (1 cm H(2)O=0.098 kPa)], high; NO ( 40 x 10(-6) NO, HNO) group and low concentration; NO (10 x 10(-6) NO, LNO) group. Indexes including haemodynamics, blood gas analysis, and mechanics of breathing were determined after MV at different time points in each group. The rabbits were sacrificed after MV lasting for 4 hours. Wet/dry weight (W/D) ratio of the lung was calculated, and the condition of alveolar exudation was observed. RESULTS: (1) Oxygenation index (PaO(2)/FiO(2)) in HNO group and LNO group were higher than those in MV group at 0.5 hour after treatment. (2) The peak pressure of airway (Ppeak) and plateau pressure of airway (Pplat) in LNO group were lower than those in MV group at 0.5, 2 and 4 hours after treatment (P<0.05 or P<0.01). Ppeak at 4 hours, Pplat at 2 hours and 4 hours were lower in HNO group as compared with those in MV group (P<0.05 or P<0.01). Pplat in LNO group was lower than that in HNO group at 2 hours and 4 hours (both P<0.01). (3) Alveolar exudation in HNO group and LNO group was milder than that in MV group (F=22.756, P<0.01). ALC in HNO group and LNO group were higher than that in MV group (F=3.965, P<0.05). The W/D ratio of lung in MV group was higher than that in HNO group, and the W/D rate in HNO group was higher than that in LNO group (F=11.740, P<0.01). (4) Lung injury score in HNO group and LNO group was higher than that in MV group, but without significant difference. CONCLUSION: iNO can reduce lung edema by increasing ALC and improving alveolar permeability, and the LNO may be more effective than HNO in treatment of early acute lung injury induced by endotoxin.

[The role of polymorphonuclear cells in lung ischemia-reperfusion injury in a canine model of pulmonary thromboembolism].

OBJECTIVE: To explore the effects of polymorphonuclear cells (PMN) on lung ischemia-reperfusion (I/R) injury in a canine model of pulmonary thromboembolism. METHODS: Fifteen dogs were divided into three groups: a sham group (n = 5), an ischemia group (n = 5) and a reperfusion group (n = 5). PMN in the whole blood were isolated with density gradient centrifugation. Apoptosis rates of the PMN was measured through flow cytometer after the cells were labeled by Annexin V-FITC before embolectomy and at 2, 4, 6 h after the operation. The myeloperoxidase (MPO) concentrations in lung homogenates were measured by ELISA. Alveolar PMN in the reperfusion lobar were observed by optical microscopy. The lung ultrastructure was studied by transmission electron microscopy. RESULTS: Alveolar PMN infiltration and the concentrations of MPO in the reperfusion group were significantly higher than those in the ischemia group (PMN (31 +/- 11) vs (8 +/- 4)/ten high power fields, MPO (11.7 +/- 1.6) vs (9.1 +/- 0.5) microg/L, P < 0.05). In the reperfusion group, abundant inflammatory cell infiltration was observed, predominantly with PMN in the alveoli. Apoptosis rates of the blood PMN at 6 h after reperfusion were much lower than before reperfusion (3.0 +/- 2.5)% vs (7.4 +/- 4.5)%, P < 0.05). At 4 and 6 h after operation, the PMN apoptosis rates in the reperfusion group were significantly lower than the ischemia group (4 h: (4.8 +/- 2.6)% vs (9.3 +/- 2.0)%, 6 h: (3.0 +/- 2.5)% vs (8.0 +/- 1.6)%, P < 0.05). PMN attaching firmly to the alveolar septum were observed by electron microscope. CONCLUSION: PMN with enhanced activities and decreased apoptosis rate, are involved in the cellular mechanisms of the lung I/R injury in this model of pulmonary thromboembolism.

[Effects of different durations of thromboembolism on blood gases, hemodynamics, pulmonary arteriography and thrombo-pathology in a canine model with selective embolization of pulmonary lobar arteries].

OBJECTIVE: To investigate the effects of different durations of thromboembolism on blood gases, hemodynamic parameters, pulmonary arteriography and thrombo-pathology in an animal model mimicking chronic pulmonary thromboembolism (PTE). METHODS: Sixteen dogs were embolized with five thrombi developed by autologous blood into the left lower pulmonary artery (n = 15) and the right lower pulmonary artery (n = 1, used to confirm the available method of selective embolization). The 15 dogs were divided into three groups: sham group (n = 5), one-week group (n = 5) and two-week group (n = 5) according to the different durations of embolization. Swan-Ganz catheter was used to guide a plastic duct, through which the thrombi were injected selectively into the left or right lower pulmonary artery by X-ray fluoroscopy. Local pulmonary arteriography of lower pulmonary arteries was taken. Blood pressure (BP), and blood gases were measured. Central venous pressure (CVP), mean pulmonary arterial pressure (MPAP), pulmonary arteriole wedge pressure (PAWP), and cardiac output (CO) were recorded, and pulmonary vascular resistance (PVR) was calculated. Each dog underwent muscular injection with tranexamic acid for one or two weeks to prevent thrombolysis. The lower lung lobe was dissected to confirm the thromboembolism after one or two weeks. The lung sections were stained with phosphotungstic acid hematoxylin (PTAH) to observe thromboemboli with optical microscopy. RESULTS: In the PTE group, PaO(2)/FiO(2), MPAP and PVR changed significantly as compared to baseline values (P < 0.05) after one hour of embolization, with MPAP increasing from (15 +/- 3) mm Hg to (21 +/- 4) mm Hg, PVR increasing from (178 +/- 114) mm Hg.s/L to (404 +/- 260) mm Hg.s/L, and PaO(2)/FiO(2) decreasing from (508 +/- 58) mm Hg to (395 +/- 100) mm Hg; these parameters returned to the baseline values one or two weeks later. After embolization, pulmonary arteriography demonstrated lower lobar artery cut-off perfusion defects. One week later, pulmonary arteriography demonstrated irregularities and stiffness of the arterial wall, enlarged proximal part of lower pulmonary artery and cut-off perfusion defects. Poor filling at embolus site was evident after embolization for two weeks. In the 1-week PTE group, organized tissue covered with the blue-purple fibrin nest was observed in the thrombus with PTAH stain. In the two-week group, the well organized thrombi were partially recanalized and surrounded and invaded by hyperplastic tissues from pulmonary artery wall. CONCLUSIONS: A canine model mimicking chronic PTE can be established by the use of fibrinolytic inhibitor tranexamic acid. Different manifestations on pulmonary arteriography and varied degree of organization of thrombi are evident at different times after embolization.

Relationship between polymorphisms of genes encoding microsomal epoxide hydrolase and glutathione S-transferase P1 and chronic obstructive pulmonary disease.

BACKGROUND: Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only 10% - 20% of chronic heavy cigarette smokers develop symptomatic disease. COPD is most likely the result of complex interactions between environmental and genetic factors. Genetic susceptibility to COPD might depend on the variations in enzyme activities that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST). In this study, we investigated the relationship between polymorphisms in the genes encoding mEH and glutathione S-transferase P1 (GSTP1) and COPD in a Chinese population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find mEH polymorphism in exon 3 (Tyr113-->His), exon 4 (His139-->Arg) and GSTP1 polymorphism in exon 5 (Ile105-->Val) in 100 COPD patients and 100 age- and sex-matched healthy controls. RESULTS: The proportion of mEH exon 3 heterozygotes was significantly higher in patients with COPD than that in the control subjects (42% vs 32%). The odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarette years was 2.96 (95% CI 1.24 - 7.09). There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and the controls. When COPD patients were non-smokers, the OR of very slow activity genotype versus other genotypes was more than 1.00; and when COPD patients were smokers (current smokers and ex-smokers), the OR was less than 1.00. There was no significant difference in GSTP1 polymorphism adjusted by age, sex, BMI and smoking between COPD patients and the controls. CONCLUSIONS: mEH exon 3 heterozygotes might be associated with susceptibility to COPD in China. The interaction might exist between mEH genotype and smoke. The gene polymorphism for GSTP1 might not be associated with susceptibility to COPD in the Chinese population.

[Association between polymorphisms in the microsomal epoxide hydrolase (mEH) gene and chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the association between polymorphisms in the microsomal epoxide hydrolase (mEH) gene and susceptibility to chronic obstructive pulmonary disease (COPD) in a Chinese population. METHODS: Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype mEH polymorphisms in exon3 (Tyr113-->His) and exon4 (His139-->Arg) in 100 COPD patients and 100 age and sex matched healthy controls. RESULTS: (1) The proportion of mEH heterozygotes in exon3 was significantly higher in the patients with COPD than that in the control subjects (42% vs 32%). The odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarettes years was 2.96 (95% CI 1.24 - 7.09). (2) There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and controls. (3) When COPD patients were nonsmokers, the OR of very slow activity genotype versus other genotypes was more than 1.00, and when COPD patients were smokers (Current smokers and ex-smokers), the OR was less than 1.00. CONCLUSIONS: (1) mEH heterozygotes in exon3 might be associated with the susceptibility to COPD in China. (2) The interaction might be existed between mEH genotype and smoke.

[Association between polymorphisms in the gene coding for glutathione S-transferase P1 and chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the association between polymorphisms in the gene coding for glutathione S-transferase P1 (GSTP1) and susceptibility to chronic obstructive pulmonary disease (COPD) in a Chinese population. METHODS: This was a pilot study of the molecular epidemiology in patients with COPD. The research design was a case-control study. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype GSTP1 polymorphisms in exon 5 in 100 COPD patients and 100 age and sex matched healthy controls. Logistic regression analysis method was used to calculate the odds ratio (OR) and the 95% confidence interval (CI). RESULT: There was no significant difference in GSTP1 polymorphisms adjusted by age, sex, body mass index and smoking between COPD patients and controls. CONCLUSION: The gene polymorphism for GSTP1 was not associated with susceptibility to COPD in the Chinese population.