[Platelet factor 4 and ß-thromboglobulin in blood plasma of patients with acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To explore the role of platelet factor 4 (PF4) and ß-thromboglobulin (ß-TG) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: A total of 71 AECOPD patients and 50 chronic obstructive pulmonary disease (COPD) patients within a stable stage were admitted into Beijing Chaoyang Hospital from January 2008 to June 2010. And another 40 healthy volunteers were selected as control group. The data of demographics, arterial blood gas analysis and pulmonary function parameters was collected and analyzed. The plasma levels of PF4 and ß-TG were measured by enzyme-linked immunosorbent assay (ELISA). Platelet count was measured by hematology analyzer. Statistical analysis was used for PF4, ß-TG and platelet count. Spearman rank correlation was used for correlation analysis. RESULTS: No differences in age and gender existed among the AECOPD, stable and control groups. The plasma level of PF4 in the AECOPD group (2.28 µg/L) was significantly higher than that of the stable group (2.01 µg/L) and control group (1.57 µg/L) (both P < 0.05). The level of ß-TG in AECOPD was 2.32 µg/L and it was significantly higher than that of the stable group (1.85 µg/L) and control group (1.29 µg/L) (both P < 0.05). The differences in platelet counts were insignificant between the AEC OPD group ((196 ± 67) ×10(9)/L), stable group ((194 ± 50) ×10(9)/L) and control group ((190 ± 48) ×10(9)/L). AECOPD group was divided into moderate, severe and very severe groups by pulmonary function parameters. The levels of PF4 and ß-TG in very severe group were significantly higher than those in moderate and severe groups (P < 0.05). A significant positive correlation was observed between PF4 and ß-TG (r = 0.518, P < 0.01). The levels of PF4 and ß-TG were negatively correlated with FEV1%, FEV1/FVC and PaO2 (all P < 0.05). CONCLUSION: Abnormal platelet activation exists in AECOPD. And the levels of PF4 and ß-TG may reflect the severity of AECOPD and can be used as the markers of estimating prethrombotic state.

[Effects of aerosolized earthworm fibrinolytic enzyme on bleomycin induced pulmonary fibrosis in rats].

OBJECTIVE: To explore the effects of aerosolized earthworm fibrinolytic enzyme (EFE) on bleomycin-induced pulmonary fibrosis in rats. METHODS: A total of 72 male SD rats were divided randomly into 3 groups of bleomycin (BLM) group with intratracheal BLM (5 mg/kg), control group with the same dose of normal saline, then after both receiving aerosolization of normal saline once daily instead of EFE, EFE group with EFE (2500 U/kg) by aerosolization once daily after BLM instillation. Lung histopathology, immunohistochemistry for transforming growth factor ß(1) (TGF-ß(1)), lung hydroxyproline contents, levels of urokinase PA (uPA), tissue plasminogen activator (tPA) and PA inhibitor 1 (PAI-1) in lung and blood were observed at Days 7, 14 and 28 of experiment, respectively. RESULTS: Compared with BLM group, pulmonary fibrosis improved and the TGF-ß(1) expression of lung tissue decreased (P < 0.01). Hydroxyproline content of lung tissue decreased in EFE group compared with BLM group ((5.8 ± 2.5) vs (9.6 ± 1.3), (6.7 ± 1.4) vs (9.7 ± 1.5), (7.5 ± 1.2) vs (9.7 ± 1.4) mg/L, P < 0.01). Compared with BLM group, the uPA levels of lung were elevated in EFE group at Days 7 and 14 ((1.04 ± 0.36) vs (0.72 ± 0.11), (0.90 ± 0.09) vs (0.75 ± 0.08) µg/L, P < 0.05). Moreover, the plasma levels uPA of increased at Days 14 and 28 ((0.32 ± 0.04) vs (0.25 ± 0.02), (0.36 ± 0.05) vs (0.28 ± 0.04) µg/L, P < 0.05). Consistently, compared with BLM group, the tPA levels of lung increased in EFE group ((4.70 ± 0.87) vs (3.01 ± 0.62), (5.72 ± 0.37) vs (3.00 ± 0.51), (6.73 ± 1.12) vs (3.18 ± 0.38) µg/L, P < 0.01) and the plasma levels of tPA also increased ((3.40 ± 0.36) vs (1.79 ± 0.38), (3.17 ± 0.37) vs (2.18 ± 0.17), (3.85 ± 0.56) vs (2.80 ± 1.06) µg/L, P < 0.01). However, compared with BLM group, the PAI-1 levels of lung decreased in EFE group ((6.04 ± 0.81) vs (8.52 ± 1.01), (6.78 ± 0.81) vs (9.81 ± 1.73), (7.63 + 0.99) vs (11.44 ± 2.54), P < 0.05) and the plasma levels of PAI-1 also decreased in EFE group ((4.82 ± 0.42) vs (6.89 ± 0.84), (5.73 ± 0.40) vs (7.30 ± 1.09), (5.64 ± 0.87) vs (7.98 ± 1.10) µg/L, P < 0.05). CONCLUSIONS: Earthworm fibrinolytic enzyme may decrease bleomycin-induced pulmonary fibrosis and TGF-ß(1) expression while increasing fibrinolytic activation. And fibrinolytic strategies are probably useful for the therapy of fibrotic lung diseases.

[Change of coagulation functions and its significance in acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To explore the changes and clinical significances of plasma D-dimer, factor X and tissue factor in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and analyze the in-depth changes of these indicators in AECOPD with co-current deep venous thrombosis (DVT). METHODS: A total of 56 AECOPD patients were divided into the DVT and non-DVT subgroups (n = 28 each). And 60 normal control subjects were recruited according to age and gender. For each subject, 2.7 ml whole blood was drawn and then the plasma levels of D-dimer, factor X and tissue factor were detected. The results were statistically analyzed with the software SPSS 13.0. And the analysis of variance was performed between the groups. RESULTS: There was no significant difference between the distribution of the AECOPD group and the control group by gender and age. Therefore two groups were comparable. And in the AECOPD group, there was no significant difference between the distribution of DVT and non-DVT subgroups by gender and age. Therefore these two subgroups were comparable as well. The value of D-dimer in the AECOPD patients was significantly higher than that in the normal control [(0.76 ± 0.30) vs (0.29 ± 0.11) mg/L, P < 0.01]; and in the AECOPD group, the value of D-dimer in the DVT subgroup was significantly higher than that in the non-DVT subgroup [(0.85 ± 0.29) vs (0.67 ± 0.28) mg/L, P < 0.05]. In the AECOPD group, the value of tissue factor was (238 ± 68) mg/L and the value of factor X (1181 ± 337) mg/L. While in the normal control group, the values were (124 ± 30) and (998 ± 260) mg/L respectively. As for tissue factor and factor X, there were significant differences between two groups (all P < 0.01). Yet in AECOPD patients, neither indicator had significant differences between the DVT and non-DVT subgroups (all P > 0.05). CONCLUSION: The blood of AECOPD patients is in a hypercoagulatory state. And an obvious rise in their plasma level of D-dimer suggests that it may be complicated with DVT.

Chemokine receptor CXCR3 is important for lung tissue damage and airway remodeling induced by short-term exposure to cigarette smoking in mice.

AIM: To investigate the role of chemokine receptor CXCR3 in cigarette smoking (CS)-induced pulmonary damage. METHODS: CXCR3 knockout (CXCR3-/-) mice were used. Differences in airspace enlargement, mRNA expression of matrix metalloproteinases (MMPs), transforming growth factor (TGF) beta1, CXCL10 in lung homogenates, and CXCL10 content in bronchoalveolar lavage (BAL) fluids and homogenates were compared between CXCR3-/- mice and wild-type (WT) mice three days after three-day CS exposures. RESULTS: The linear intercept was significantly less in CXCR3-/- mice than in WT mice (30.1+/-0.9 microm vs 40.3+/-2.4 microm, P<0.01). Morphologically, collagen was deposited less around airways and vessels in CXCR3-/- mice. The lung hydroxyproline content was significantly lower in CXCR3-/- mice than in WT mice (6.0+/-1.0 microg/mL vs 12.0+/-1.6 microg/mL, P<0.05). Profoundly lower mRNA expression of MMP2, MMP12, TGF beta 1, and CXCL10 was seen in lung homogenates from CXCR3-/- mice. CXCL10 concentrations in BAL fluid and lung homogenates were significantly lower in CXCR3-/- mice than in WT mice (BAL fluid: 19.3+/-1.4 pg/mL vs 24.8+/-1.6 pg/mL, P<0.05; lung homogenates: 76.6+/-7.0 pg/mL vs 119.5+/-15.9 pg/mL, P<0.05). CONCLUSION: CXCR3 is important in mediating lung tissue damage and airway remodeling following a short-term CS insult, possibly through up-regulation of CXCL10 and inducement of mRNA expression of MMPs. Targeting CXCR3 may be helpful for prevention of CS-induced pulmonary pathology.

[Hemodynamic effects of synchronous and asynchronous independent lung ventilation with different levels of positive end-expiratory pressure and tidal volumes on unilateral lung injury in dogs].

OBJECTIVE: To investigate the effects of asynchronous independent lung ventilation and synchronous independent lung ventilation with different levels of positive end-expiratory pressure (PEEP) and tidal volumes on hemodynamics and gas exchange in dogs with a hydrochloric acid induced acute lung injury. METHODS: Twelve dogs with hydrochloric acid induced acute lung injury (left lung) were ventilated with volume controlled ventilation (VCV). The animals were randomly divided by random digit table into 2 groups. The first group (group NS, n = 6) received asynchronous independent lung ventilation with the left lung PEEP 10 cm H2O (1 cm H2O = 0.098 kPa), VT 3.5 ml/kg and the right lung PEEP 0 cm H2O, VT 5 ml/kg. The second group (group S, n = 6) received synchronous independent lung ventilation with the parameters as same as group NS. HR, mABP, mPAP, PAWP, CO and blood gas levels were measured during ventilation with different levels of PEEP (15, 20, 25 cm H2O) and VT (5, 7.5, 10 ml/kg) for 30 min. RESULTS: (1) After 30 min ventilation, no significant differences for hemodynamics and gas exchange were found between group NS and group S when Left lung PEEP was 15 or 20 cm H2O and VT was 5 or 7.5 ml/kg. (2) After 30 min ventilation, HR, mABP, CO, PaO2/FiO2, SvO2 in group NS [(98 ± 8) beats/min, (84 ± 6) mm Hg (1 mm Hg = 0.133 kPa), (1.10 ± 0.13) L/min, (199 ± 14) mm Hg and (55 ± 6)%, respectively] were significantly lower than those in group S [(124 ± 9) beats/min, (103 ± 7) mm Hg, (1.52 ± 0.28) L/min, (221 ± 15) mm Hg and (62 ± 4)%, respectively] when PEEP was 25 cm H2O (all P < 0.01). (3) After 30 min ventilation, HR, mABP, CO, PaO2/FiO2, SvO2 in group NS [(92 ± 6) beats/min, (83 ± 9) mm Hg, (1.23 ± 0.08) L/min, (196 ± 8) mm Hg and (57 ± 2)%, respectively] were significantly lower than those in group S [(122 ± 10) beats/min, (104 ± 4) mm Hg, (1.56 ± 0.12) L/min, (216 ± 14) mm Hg and (63 ± 4)%, respectively] when VT was 10 ml/kg (all P < 0.01). CONCLUSIONS: In this animal model, the hemodynamics kept stable when the difference between the left lung PEEP and the right lung PEEP was less than 20 cm H2O. Synchronous independent lung ventilation caused less hemodynamic compromise when higher PEEP (> 25 cm H2O) was used because of the marked asymmetry in the mechanics of the 2 lungs.

[The effect of simvastatin on alveolar epithelial cells in cigarette smoking-induced emphysema].

OBJECTIVE: to explore the effect of simvastatin on alveolar epithelial cells and the expression of vascular endothelial growth factor (VEGF) in cigarette smoking-induced emphysema in rats. METHODS: twenty-four, 12-week-old healthy male and female Wistar rats were randomly divided into 4 groups of 6 each: a control (W) group, a smoking (Sm) group, a simvastatin (St) group, and a smoking-simvastatin (SmSt) group. The rats were simultaneously fed, and kept in individual cages for 16 weeks. The VEGF level in lung tissue and bronchoalveolar lavage fluid (BALF) of each group was measured by ELISA. The expression of VEGF mRNA was determined by RT-PCR. The expressions of VEGF and proliferating cell nuclear antigen (PCNA) were determined by two-step immunohistochemistry assay. One-way ANOVA and LSD-t test were used for statistical analysis. RESULTS: the percentage of PCNA-positively stained alveolar epithelial cells was significantly higher in the SmSt group [(10.3 ± 2.0)%] than in the Sm group [(4.8 ± 0.8)%]. The levels of VEGF in BALF and lung tissue homogenate of the SmSt group [(187 ± 15) ng/L and (6782 ± 50) ng/L] were similar to the W group [(200 ± 20) ng/L and (7558 ± 330) ng/L], but were significantly higher than that in the Sm group [(71 ± 16) ng/L and (4149 ± 110) ng/L]. VEGF expression in alveolar and bronchial epithelial cells of rats in the SmSt group [(67.7 ± 5.0)% and (49.0 ± 3.0)%], was similar to the W group [(68.3 ± 3.3)% and (51.3 ± 2.9)%]. But the level of VEGF expression was significantly increased as compared to that in the Sm group [(27.0 ± 5.9)% and (16.3 ± 2.7)%]. SmSt group vs Sm group t = 1.117 - 12.001, all P < 0.01. CONCLUSIONS: simvastatin ameliorated the development of cigarette smoke-induced COPD in rats, partly by promoting alveolar epithelial cell proliferation and up-regulating the expression of VEGF.

[Expression of intercellular cell adhesion molecule-1, interleukin-10 and the activation of activator protein-1 in ventilator-induced lung injury in rabbits].

OBJECTIVE: To study the expression of intercellular cell adhesion molecule-1 (ICAM-1), Interleukin-10 (IL-10) and the activation of transcription factor activator protein-1 (AP-1) in a rabbit model of ventilator-induced lung injury (VILI) and therefore to explore their possible role in VILI. METHODS: The VILI model was established by mechanical ventilation with a large tide volum (V(T)) of 40 ml/kg. Forty healthy male New Zealand rabbits were randomly divided into 5 groups: a control group without mechanical ventilation, a conventional ventilation group, and injurious ventilation with large V(T) for 1 h group, 2 h group and 4 h group. The concentrations of soluble ICAM-1 (sICAM-1) and IL-10 in lung homogenates were measured by enzyme-linked immunosorbent assay (ELISA). The level of mRNA was measured by semiquantitative transcription-polymerase chain reaction (RT-PCR). The DNA-binding activity of AP-1 was measured by electrophoretic mobility shift assay (EMSA). The partial arterial blood pressure of oxygen (PaO2), myeloperoxidase (MPO) in lung homogenate, wet lung weight to dry lung weight ratio (W/D) were observed. RESULTS: (1) The concentrations of sICAM-1 in large V(T) for 2 h group (23 ± 5) ng/L and 4 h group (35 ± 5) ng/L were higher than that in the conventional ventilation group (16 ± 4) ng/L (P all < 0.05), and that in the Large V(T) for 4 h group were higher than that in 1 h group (19 ± 4) ng/L and 2 h group (P all < 0.01). The concentrations of IL-10 in the large V(T) for 2 h group (24 ± 4) ng/L and 4 h group (26 ± 5) ng/L were higher than that in the conventional ventilation group (15 ± 2) ng/L (P all < 0.05), and that in the Large V(T) for 4 h group was higher than that in the 1h group (19 ± 4) ng/L(P < 0.05). The level of ICAM-1 mRNA in the large V(T) for 2 h group (1.18 ± 0.19) and 4 h group (1.29 ± 0.19) were higher than that in the conventional ventilation group (0.84 ± 0.13) (P all < 0.05), and that in Large V(T) for 4 h group was higher than that in 1 h group (0.96 ± 0.24) (P < 0.05). The level of IL-10 mRNA in the large V(T) for 4 h group (1.13 ± 0.17) was higher than that in the conventional ventilation group (0.84 ± 0.20) and Large V(T) for 1 h group (0.86 ± 0.12) (P all < 0.05). (2) The DNA-binding activity of AP-1 in the large V(T) for 2 h group (33.77 ± 8.23) and 4 h group (38 ± 9) were higher than that in the conventional ventilation group (23 ± 9) (P all < 0.01), and that in Large V(T) for 4 h group was higher than that in 1h group (25 ± 9) (P < 0.01). (3) Histopathological findings demonstrated that diffused alveolar damage induced by mechanical ventilation was worse with time, and after mechanical ventilation with large V(T) for 2 h, the level of MPO began to increase, and for 4 h the PaO2 reduced and the W/D increased. CONCLUSIONS: ICAM-1 and IL-10 took part in the inflammatory responses of VILI, and their up-regulation maybe due to the increase of their mRNA. Nuclear transcription factor AP-1 maybe involved in the transcriptional regulation mechanisms of these inflammatory mediators.

Decreased plasma soluble thrombomodulin levels as a risk factor for pulmonary thromboembolism.

OBJECTIVE: To observe the changes of the plasma soluble thrombomodulin (sTM) concentrations in patients with pulmonary thromboembolism (PTE) and assess the association between plasma sTM concentration and the risk of PTE. PATIENTS AND METHODS: We measured plasma concentrations of sTM, protein C (PC) and protein S (PS) and examined the association between those plasma markers and the risk of PTE in 72 selected PTE patients and 70 controls. RESULTS: Significant difference was identified in plasma sTM level between overall PTE patients and controls. Female PTE patients had statistically lower sTM concentrations than male patients. A positive linear correlation was found between plasma sTM concentration and age in female patients. Decreased plasma sTM concentration was associated with a continuously and progressively increased risk for PTE in women. The concentrations of plasma PC and PS did not differ between groups and no significant quantitative association was identified between the risk of PTE and the levels of plasma PC or PS. CONCLUSION: Decreased plasma sTM concentration is associated with an increased risk of PTE in women.

[Effect of guishen zhiyang recipe for treatment of patients with senile pruritus of blood-deficiency and Gan-hyperactive syndrome type and its impact on stem cell factor and dynorphin].

OBJECTIVE: To explore the mechanism of Chinese medicinal therapy for nourishing blood and softening Gan in treating senile pruritus through observing the impact of Guishen Zhiyang Recipe (GZR) on serum levels of stem cell factor (SCF) and dynorphin (DYN) in patients suffered from the disease of blood-deficiency and Gan-hyperactive syndrome type (BDGH). METHODS: Sixty patients with senile pruritus were equally randomized into two groups, the patients in the treated group (33 cases) were treated by GZR, and those in the control group (28 cases) were treated by Fuyang Granule, all for 8 weeks. Changes of symptoms and skin lesions as well as blood levels of SCF and DYN were observed before and after treatment. RESULTS: Three patients were rejected from the treated group. Twenty patients in the treated group were cured after treatment, the cure rate being 66.7%, which was significantly higher than that in the control group (10 patients, 35.7%, P < 0.05). Levels of SCF and DYN in the treated group significantly lowered after treatment (all P < 0.01), and were lower than those in the control group (P < 0.05 and P < 0.01, respectively). CONCLUSION: GZR shows favorite effect in treating senile pruritus of BDGH type and it may be achieved by regulating SCF and DYN levels to improve the pruritus associated inflammatory media.

Acute pulmonary inflammation is inhibited in CXCR3 knockout mice after short-term cigarette smoke exposure.

AIM: CXCR3, via binding its specific ligand CXCL10, plays an important role in cigarette smoke (CS)-induced pulmonary inflammation. CXCR3 is preferentially expressed in activated T cells (chiefly CD8+ T cells). The purpose of this study was to investigate the role of CXCR3 in CS-induced pulmonary injury using CXCR3 gene-deficient (CXCR3-/-) mice. METHODS: Differences in the infiltration of inflammatory cells and CD8+ T cells and the expression of inflammatory mediators and chemokines in the bronchoalveolar lavage fluid and lungs at the mRNA and protein levels were compared between CXCR3-/- mice and wild-type (WT) mice at 2 h after 3 d of CS exposure. RESULTS: Compared with their WT counterparts, the CXCR3-/- mice showed alleviated inflammation, as evidenced by fewer inflammatory cells, particularly cytotoxic CD8+ T cells, in bronchoalveolar lavage fluid and lung tissues. At both the mRNA and protein levels, there were significantly lower levels of inflammatory and chemotactic cytokines, including TNF-alpha, interleukin-8, interferon-gamma, transforming growth factor-beta1, and CXCL10 in the CXCR3-/- mice. CONCLUSION: Our data show that CXCR3 is important in recruiting inflammatory cells (particularly CD8+ T cells) into the airways and lungs, as well as initiating inflammatory and fibrotic cytokines release at 2 h following a short-term CS insult. CXCR3 could be a novel target for the treatment of pulmonary inflammation induced by CS.

[Effects of prone position ventilation combined with recruitment maneuver on oxygenation and shunt in canines with acute respiratory distress syndrome].

OBJECTIVE: To evaluate the effects of prone position ventilation (PPV) combined with recruitment maneuver (RM) on oxygenation and intrapulmonary shunting in oleic acid-induced acute respiratory distress syndrome (ARDS) in canines while ventilated with lung protective ventilation strategy. METHODS: ARDS was induced by oleic acid in 24 dogs, and the animals were ventilated with volume controlled ventilation (VCV), 16 cm H2O (1 cm H2O = 0.098 kPa) of positive end-expiratory pressure (PEEP) and small tidal volumes (V(T) 10 ml/kg). All the dogs were randomly divided by random digit table into 4 groups (6 each), a control group (supine position, SP group), a prone position group (PP group), a supine position + RM group (SPRM group), and a prone position + RM group (PPRM group), and then were ventilated by VCV for 4 h. Arterial and mixed venous blood gas analyses were measured. Data were analyzed using the SPSS for windows (version 11.5). Results were expressed as x +/- s. Homogeneity of variance test was performed. The differences in means were calculated using one-way ANOVA. Post-hoc multiple comparisons of means were performed using Least Significant Difference. Nonparametric tests for several independent samples were performed to compare differences between the ranks in the groups studied. P value of < 0.05 was considered statistically significant. RESULTS: (1) At 15 min, PaO2/FiO2 in the SPRM group, the PP group and the PPRM group [(368 +/- 45) mm Hg (1 mm Hg = 0.133 kPa), (349 +/- 80) mm Hg, ( 423 +/- 43) mm Hg, respectively] was significantly higher than that in the SP group [(269 +/- 72) mm Hg, q = 2.77, 2.23, 4.31, respectively, all P < 0.05]. At 2 h, PaO2/FiO2 in the PP group and the PPRM group [(401 +/- 82) mm Hg, (416 +/- 23) mm Hg, respectively] was significantly higher than that in the SP group [(232 +/- 40) mm Hg, q = 3.99, 4.35, respectively, all P < 0.05]. At 4 h, PaO2/FiO2 in the PPRM group [(384 +/- 68) mm Hg] was significantly higher than that in the SP group [(256 +/- 75) mm Hg], that in the SPRM group [(267 +/-92) mm Hg] and that in the PP group [(284 +/- 83) mm Hg, q = 2.75, 2.56, 2.17, respectively, all P < 0.05]. (2) Intrapulmonary shunt (Q(S)/Q(T)) in the PP group was significantly decreased compared with that in the SP group from 30 min to 2 h [30 min (9.9 +/- 4.4)% vs (15.0 +/- 1.6)%, 1 h (9.7 +/- 4.5)% vs (16.0 +/- 2.0)%, 2 h (8.3 +/- 4.6)% vs (16.2 +/- 1.8)%, q = 2.86, 3.00, 3.65, respectively, all P < 0.05]. The Q(S)/Q(T), in the PPRM group was significantly decreased compared with that in the SP group from 30 min to 4 h [30 min (10.0 +/- 1.0)% vs (15.0 +/- 1.6)%, 1 h (10.4 +/- 2.7)% vs (16.0 +/- 2.0)%, 2 h (10.2 +/- 0.7)% vs (16.2 +/- 1.8)%, 4 h (10.1 +/- 1.1)% vs (15.7 +/- 1.7)%, q = 2.80, 2.67, 2.75, 2.99, respectively, all P < 0.05]. CONCLUSIONS: On the basis of small tidal volume lung and PEEP protective ventilation strategy, combining prone position and recruitment maneuver was more effective and showed a synergistic effect on improving oxygenation and intrapulmonary shunt.

[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 effects of different ventilatory modes and spontaneous breathing after recruitment maneuver in acute respiratory distress syndrome. Experiment with dogs].

OBJECTIVE: To investigate the role of different ventilatory modes and spontaneous breathing (SB) in prevention of derecruitment in acute respiratory distress syndrome (ARDS). METHODS: Eighteen dog ARDS models were established by injection of oleic acid into the central vein and ventilated with volume controlled ventilation (VCV,) with the positive end expiratory pressure (PEEP) of 16 cm H(2)O, tidal volume (V(T)) of 10 ml/kg, and respiratory rate (RR) of 30 bpm, and the steady state in this mode was defined as baseline (0 min). After the baseline state was reached, all dogs accepted recruitment maneuver (RM) in pressure controlled ventilation (PCV) mode at the level of 15 cm H(2)O and PEEP of 35 cm H(2)O for 1 min, and then assigned into three groups and ventilated for 4 hs: VCV group (VCV with V(T) of 15 ml/kg), PCV group in which the peak inspiratory airway pressure was adjusted for keeping 15 ml/kg of V(T), and SB grouping which PCV with SB activity and inspiratory airway pressure were adjusted for keeping 15 ml/kg of V(T). PEEP of 10 cm H(2)O, RR of 20 bpm, and inspiratory/expiratory ratio of 1/2 were kept for all animals. Four hours later the dogs were killed and their lungs were taken out. RESULTS: (1) The lower inflection points were identified as 16.1 +/- 1.9, 17.4 +/- 1.5, and 17.1 +/- 1.6 cm H(2)O for the VCV, PCV, and SB group respectively. (2) After RM, the PaO(2) levels of the PCV and SB groups were kept higher than baseline, but the PaO(2) level was as same as that in the baseline state in the VCV group. Compared with the VCV group, higher PaO(2) the PaO(2) level 30 min after RM in the SB group was found (P < 0.05). The intrapulmonary shunt 5 min, 30 min and 1 hr after RM in the SB group were all lower than those in the VCP group, however, not significantly (P = 0.077, 0.058, 0.076). (3) Compared with baseline levels, the plateau pressure and mean airway pressure in all animals were decreased significantly after RM. The plateau pressure in the SB group was significantly lower than that in the VCV group (P < 0.05). CONCLUSION: PCV with spontaneous breathing activity can offset the effect of antiderecruitment for lower PEEP; it would be more safe and effective than VCV.

[Changes of blood coagulative and fibrinolytic system and function of pulmonary vascular endothelium after therapy in patients with acute pulmonary thromboembolism].

OBJECTIVE: To study the changes of blood coagulative and fibrinolytic system and the function of pulmonary vascular endothelium in the course of acute pulmonary thromboembolism (PTE) and after anticoagulant or thrombolytic treatment. METHODS: Twenty patients with acute non-massive PTE, 10 males and 10 females, aged (57 +/- 11) underwent anticoagulant treatment and 17 sex-, and age-matched acute massive PTE patients underwent thrombolytic treatment. The plasma level of D-dimer (D-D), thrombomodulin (TM), protein C (PC), protein S (PS), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and antithrombin-III (AT-III) activity were measured by ELISA before and after normal subjects severed as control group were included in the study. The plasma level of D-D, PS, PC, TM, t-PA and PAI-1 were measured by a method of ELISA before the treatment and six days after the anticoagulant treatment or 24 hours after the thrombolytic treatment. AT-III activity was measured by chromo-substrate method at the same time points. Forty sex- and age-matched healthy persons were used as controls. RESULTS: The plasma levels of D-D, t-PA, PS, and TM level of the anticoagulant group were all significantly higher and the AT-III activity of the 2 treatment groups was significantly lower than those of the controls before treatment (all P < 0.05); the plasma levels of D-D, t-PA, PAI-1, PS, and TM of the thrombolytic group were ala significantly higher and the AT-III activity was significantly lower than those of the control group before the treatment (all P < 0.05). After anticoagulant therapy, the plasma levels of D-D, t-PA, PS, and PC were significantly lower than those before treatment (all P < 0.05), however, the plasma levels of PAI-1, TM, and AT-III activity after treatment did not differ significantly from those before treatment. The plasma levels of D-D, t-PA, PS, PC, and TM after treatment of the thrombolytic group were all significantly lower than those before treatment (all P < 0.05), however, the plasma levels of PAI-1, TM, and AT-III activity after treatment did not differ significantly from those before treatment. CONCLUSION: Apparent imbalance in the blood coagulative and fibrinolytic system and pulmonary vascular endothelium damage occur in the patients with acute PTE. Combination tests of plasma D-D, AT-III, PS, PC, TM, t-PA and PAI-1 can give a more comprehensive explanation of the imbalance in the blood coagulative and fibrolytic system. Anticoagulant treatment and thrombolytic treatment play important roles in the regulation of the imbalance of coagulative and fibrinolytic system and protection of the function of pulmonary vascular endothelium of PTE patients.

[Effect of TCM treatment for dissolving phlegm and dispelling stasis on plasma protein and thrombomodulin in patients with acute cerebral infarction].

OBJECTIVE: To observe the clinical effect of TCM treatment for dissolving phlegm and dispelling stasis (DP-DS) on acute cerebral infarction (ACI) and its influences on plasma protein C and S and soluble thrombomodulin (TM). METHODS: One hundred and twenty-two patients were randomly assigned to two groups, the treated group (62 cases) and the control group (60 cases). They were all treated with the conventional treatment, and DP-DS treatment was given to the treated group additionally. The treatment course was 14 days. The changes in scores of TCM syndrome and neurofunction impairment (NIHSS), levels of plasma protein C (PC), protein S (PS) and TM before and after treatment in the two groups were observed. RESULTS: The total effective rate of TCM syndrome in the treated group was higher than that in the control group (P= 0.00). After treatment, NIHSS in the two groups was significantly different (P=0.00), and the score in the treated group was superior to that in the control group (P = 0.00). NIHSS score and levels of PC and PS were improved in both groups (P = 0.024, 0.028), and the improvement of PC in the treated group was superior to that in the control group respectively (P = 0.049). But no significant change of TM was shown after treatment. CONCLUSION: TCM DP-DS treatment shows significant effect in improving TCM syndrome and neurofunction impairment of the patients with acute cerebral infarction, and raise the levels of PC and PS.

[The changes of serum enzymes and cardiac troponin I in patients with acute pulmonary thromboembolism].

OBJECTIVES: To investigate the changes of serum enzymes and cardiac troponin I (TnI) in patients with acute pulmonary thromboembolism (PTE). The relationships between these changes and the pulmonary artery pressure, the right ventricular function and the prognosis were evaluated. METHODS: This prospective multi-centre trial included 519 patients with confirmed PTE from 24 collaborating hospitals, with 54 cases of massive PTE, 195 sub-massive PTE and 270 non-massive PTE. Thrombolytic treatment with urokinase or recombinant tissue plasminogen activator (rt-PA) was administered for massive and sub-massive PTE patients; anti-coagulative therapy with unfractionated heparin or low molecular weight heparin was used for non-massive PTE. RESULTS: The values of serum ALT, AST, CPK and LDH before treatment in massive PTE [(74 +/- 33), (88 +/- 40), (157 +/- 75), (419 +/- 264) U/L] were significantly higher than those in sub-massive [(52 +/- 21), (43 +/- 18), (75 +/- 30), (284 +/- 176) U/L] and non-massive cases [(38 +/- 13), (35 +/- 11), (78 +/- 24), (239 +/- 178) U/L] (P < 0.05). The value of serum ALT at day 7 (84 +/- 39 U/L) in the unfractionated heparin sub-group of the non-massive PTE was significantly higher than that (67 +/- 26 U/L) in the low molecular weight heparin sub-group (P = 0.045). Of the 45 cases with high pulmonary pressure > 80 mm Hg (1 mm Hg = 0.133 kPa), 24 (54.4%) cases showed high serum LDH (P = 0.032) and 17 (41.5%) high serum ALT (P = 0.049). Of the 169 cases with right ventricular dysfunction, 68 (40.2%) cases showed high serum LDH (P = 0.049) and 76 (45.5%) high serum ALT (P = 0.037). Of the 48 cases with poor prognosis, 15 (30.8%) cases showed high serum LDH (P = 0.039) and 26 (54.5%) high serum ALT (P = 0.022). Of the 39 cases with TnI > or = 0.07 microg/L, 24 (63.3%) cases were complicated with decreased right ventricular function (P < 0.01) and 8 (24.2%) with poor prognosis (P = 0.034). CONCLUSIONS: The values of serum ALT, AST, CPK, LDH and TnI are increased in acute PTE. Unfractionated heparin results in higher levels of ALT than lower molecular weight heparin. The increase of serum ALT, LDH and TnI is correlated with pulmonary artery pressure, right ventricular function and the prognosis of the PTE. These changes may be useful in the risk stratification of PTE patients.

[Effects of bone marrow mesenchymal stem cells on bleomycin induced pulmonary fibrosis in rats].

OBJECTIVE: To study the effects of bone marrow mesenchymal stem cells (MSC) on pulmonary fibrosis. METHODS: Bone marrow MSC were harvested from 6 week old male SD rats. Forty-eight female SD rats were randomly divided into six groups. The pulmonary fibrosis models were made by intratracheal instillation of bleomycin (5 mg/kg in 0.3 ml normal saline). The normal controls received intratracheal instillation of NS instead of bleomycin. On the 1st and 7th day after bleomycin administration, the rats received MSC infusion or a same amount of phosphate buffer solution (PBS) as controls via the tail vein, respectively. The rats were sacrificed by the 28 day of experiment, and the pathologic changes and hydroxyproline contents of the lung tissues were investigated. The sry gene of Y chromosome was detected by polymerase chain reaction (PCR). RESULTS: For rats receiving MSC on the 1st and 7th day after bleomycin administration, the lung fibrotic scores were 1.0 +/- 0.2 and 1.6 +/- 0.5, respectively, significantly decreased as compared with rats receiving no MSC (2.5 +/- 0.5 & 2.3 +/- 0.8, respectively). The hydroxyproline contents of lung tissue were (83 +/- 17) microg/mg and (96 +/- 20) microg/mg, also significantly decreased as compared with rats receiving no MSCs [(123 +/- 32) microg/mg & (127 +/- 34) microg/mg, respectively]. Earlier administration of MSCs resulted in more significant improvement of lung injury. The sry gene (322 bp) was detected in lungs of female rats receiving MSC on the first day of bleomycin induced lung injury. CONCLUSIONS: MSC may be involved in the repair of lung injury, especially in the early stage. MSCs are effective in preventing bleomycin induced lung injury and fibrosis.

[The effect of VEGF antisense oligonucleotides combined with low molecular weight heparin on the growth and metastasis of mice Lewis lung cancer].

OBJECTIVE: To investigate the inhibitory effect of vascular endothelial growth factor (VEGF) antisense oligonucleotides or/and dalteparin sodium (fragmin) on tumor growth and metastasis of mice Lewis lung cancer. METHODS: 40 mice with Lewis lung cancer were randomizedly divided into five groups: control group, VEGF antisense oligonucleotides (ASODN) group, VEGF mismatch sense oligonucleotides (MSODN) group, low molecular weight heparin (LMWH) group, and combined group. Sodium chloride, VEGF-ASODN, VEGF -MSODN, fragmin, and VEGF-ASODN plus fragmin were given respectively (once every two days, 15 times altogether). The volume and weight of subcutaneous tumors were measured, and the rates of lung metastasis were detected by HE staining. The microvessel density (MVD) in tumor mass were measured by immunohistochemistry staining. VEGF protein level in tumor tissue were detected by Western blot assay. RESULTS: After treatment, the tumor growth inhibitory rates were 47.34%, 27.31% and 59.03%, and the rates of lung metastasis were 37.5%, 37.5% and 25% in ASODN, LMWH, and the combined group, respectively. Tumor MVD and VEGF protein expression of the above three groups were lower than those of the control group. There was a significant difference in regard to the tumor growth inhibitory rates and MVD between the above three treated groups and the control group as well as the MSODN group (P < 0.05). CONCLUSIONS: VEGF-ASODN and fragmin may down-regulate VEGF gene expression and inhibit angiogenesis, Combined use of fragmin can enhance anti- tumor effect of VEGF-ASODN.

[Relationship between polymorphisms of plasminogen activator inhibitor-1 promoter gene and pulmonary thromboembolism in Chinese Han population].

OBJECTIVE: To determine the prevalence of polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G polymorphisms in Chinese Han population and to investigate whether they are associated with pulmonary thromboembolism (PTE). METHODS: Samples of peripheral venous blood were collected from 101 patients with PTE diagnosed by high probability of lung ventilation/perfusion scan and/or multi-slice CT pulmonary angiography (CTPA) as well as medical history and clinical manifestations, 67 males and 34 females, aged 48 +/- 15, and 101 age and sex-matched healthy controls from the same geographic area as controls. The genome DNA was extracted from the whole blood using potassium iodide-phenol-chloroform method. Polymerase chain reaction (PCR), denaturing high performance liquid chromatography (DHPLC), and sequence analysis were used to screen the single nucleotide polymorphisms and the genotype distribution of -675 4G/5G located in the promoter region of the PAI-1 gene. RESULTS: The frequencies of the allele 4G of PAI-1 gene in the controls were 0.495, significantly lower than in the PTE patients (0.733, chi(2) = 24.060, P < 0.01). The frequencies of the allele 5G of PAI-1 gene in the controls were 0.505, significantly higher than that in the PET patients. The genotype frequency of 4G4G of the PET patients was 57.4%, significantly higher than that of the controls (30.7%, P = 0.000). The genotype frequencies of 4G5G and 5G5G of the PET patients were 31.7% and 10.9% respectively, not significantly different from those of the controls (37.6 and 31.7% respectively). The presence of 4G allele of PAI-1 gene was found to be a greater risk factor for PTE. In comparison with the controls, the OR of 4G4G + 4G5G, 4G4G, and 4G5G in the PET patients were 3.794 (1.786 - 8.060), 5.443 (2.416 - 12.260), and 2.450 (1.067 - 5.623) respectively with the P values of 0.001, 0.000, and 0.035 respectively. CONCLUSION: The 4G/5G and 4G/4G genotypes are associated with the pathogenesis of PET.T.