Varied response of the pulmonary arterial endothelium in a novel rat model of venous thromboembolism.

BACKGROUND: The experimental studies of venous thromboembolism (VTE) as an entity and the response of the pulmonary arterial endothelium after VTE are still rare. The objective of this study was to observe changes in the pulmonary arterial endothelium using a novel rat model of VTE. METHODS: Rats were allocated to the VTE (n = 54) or control groups (n = 9). The left femoral vein was blocked using a microvessel clip to form deep vein thrombosis (DVT). One, four or seven-day-old thrombi were injected into the right femoral vein to induce DVT-pulmonary thromboembolism (DVT-PTE). The rats were sacrificed 1, 4 or 7 days later (D(n(1,4,7)) P(n(1,4,7)) subgroups (n = 6)), and the lungs were examined using light and electron microscopy. RESULTS: On gross dissection, the rate of DVT formation was higher on day 1 (D(1)P(n): 100%, 18/18) than day 4 (D(4)P(n): 83%, 15/18; χ(2) = 5.900, P = 0.015) or day 7 (D(7)P(n): 44%, 8/18; χ(2) = 13.846, P = 0.000). On gross dissection, the positive emboli residue rate in the pulmonary arteries was lower in the D(1)P(n) subgroup (39%, 7/18) than the D(4)P(n) (73%, 11/15; χ(2) = 3.915, P = 0.048) and D(7)P(n) subgroups (100%, 8/8; χ(2) = 8.474, P = 0.004); however, light microscopy indicated the residual emboli rate was similar in all subgroups. Hyperplasia of the pulmonary arterial endothelium was observed 4 and 7 days after the injection of one-day-old or four-day-old thrombi. However, regions without pulmonary arterial endothelial cells and intra-elastic layers were observed one day after injection of seven-day-old thrombi. CONCLUSIONS: This novel model closely simulates the clinical situations of thrombus formation and is ideal to study pulmonary endothelial cell activation. The outcome of emboli and pulmonary arterial endothelial alterations are related to the age and nature of the thrombi.

[Protective effects of rosiglitazone intervention on monocrotaline-induced pulmonary arterial hypertension in rats and related inflammatory mechanisms].

OBJECTIVE: To investigate the protective effects of rosiglitazone intervention on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats and the possible mechanisms. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into 4 groups: control group with a subcutaneous injection of normal saline. PAH group, high-dose and low-dose rosiglitazone intervention groups all with a subcutaneous injection of MCT and then gastric infusion of normal saline (1.5 ml/d), rosiglitazone (5, 2.5 mg·kg(-1)×d(-1)). At Day 21, the mean pulmonary arterial pressure (mPAP) was detected by right heart catheter. Then rats were sacrificed and their lungs extracted. Perivascular inflammation was scored with the subjective scale of 0 to 4. The tunica media thickness percentage of small pulmonary arteries (WT%) of rats was calculated. Interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and monocyte chemotactic protein 1 (MCP-1) of lung tissue were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the PAH group ((37 ± 5) mm Hg (1 mm Hg = 0.133 kPa), 45.5% ± 5.5%), the mPAP and WT% of the high-dose ((27 ± 4) mm Hg, 13.1% ± 3.9%) and low-dose ((28 ± 4) mm Hg, 16.7% ± 1.7%) rosiglitazone intervention group were significantly lower (P < 0.01), but were still higher than those of the control group ((17 ± 3) mm Hg, 8.9% ± 2.3%) (P < 0.05 or P < 0.01). The perivascular inflammation score and levels of IL-6, TNF-α, MCP-1 of high-dose and low-dose rosiglitazone intervention groups were significantly lower than those of the PAH group (P < 0.01). Compared with the low-dose rosiglitazone intervention group, all the above indices of the high-dose rosiglitazone intervention group appeared much lower (P > 0.05). CONCLUSION: The protective effects of rosiglitazone against MCT-induced PH are correlated with drug dose and may be due to the inhibition of inflammation.

Additive effect of tadalafil and simvastatin on monocrotaline-induced pulmonary hypertension rats.

OBJECTIVES: Tadalafil, an oral phosphodiesterase type-5 inhibitor, induces pulmonary vasorelaxation by inhibiting the breakdown of cyclic guanosine monophosphate whereas simvastatin, an oral 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor, has been shown to reverse pulmonary hypertension (PH) and attenuate vascular remodeling in animal models of pulmonary hypertension. We investigated whether the combination of tadalafil and simvastatin, which has different mechanisms of action, is superior to either drug alone in a rat model of monocrotaline-induced PH. METHODS: Male Sprague-Dawley rats were randomized to gavage with a vehicle, tadalafil (10 mg/kg/day), simvastatin (2 mg/kg/day), or tadalafi + simvastatin 21 days after the monocrotaline (60 mg/kg) injections. The hemodynamic and histological changes in the pulmonary arterioles, right heart hypertrophy, interleukin 6 (IL-6) levels and perivascular inflammation in the lungs were measured 35 days after monocrotaline exposure. RESULTS: The combination of tadalafil and simvastatin showed significantly more improvement in the mean pulmonary hypertension pressure (mPAP) and right ventricular hypertrophy compared with each monotherapy (p < 0.05). Combination therapy had additive effects on the increases in lung IL-6 levels and the perivascular inflammation score. CONCLUSIONS: These results suggest that the combination of tadalafil and simvastatin bears promise as an approach to treat PH, especially PH associated with inflammation.

Simvastatin protects against the development of monocrotaline-induced pulmonary hypertension in rats via a heme oxygenase-1-dependent pathway.

Heme oxygease-1 (HO-1) is the rate-limiting enzyme in heme catabolism. Induction of HO-1 has been shown to have vasodilatory, anti-inflammatory, and proapoptotic effects. More recently, experimental studies suggested the potential of simvastatin as a novel therapy for pulmonary hypertension (PH); however, the underlying mechanism remains to be investigated. The aim of this study was to evaluate whether HO-1 is required for the pulmonary vascular protective effects of simvastatin. Simvastatin (2 mg/kg/day) was administered once daily to rats for 4 weeks after monocrotaline (MCT) injection. Zn-protoporphyrin (Znpp), a potent inhibitor of HO, was used to confirm the role of HO-1. The hemodynamic changes, right heart hypertrophy, interleukin-6 (IL-6) level, and HO-1 protein expression in lungs were measured at day 28. Simvastatin significantly ameliorated mean pulmonary arterial hypertension (20.6 mm Hg). In addition, perivascular infiltration of inflammatory cells and the level of IL-6 were decreased in simvastatin treatment group. Simvastatin also increased significantly lung HO-1 protein expression. Inhibiting HO-1 using Znpp resulted in a loss of the effect of simvastatin in MCT rats. These results suggest that HO-1 expression is critical for the vascular protective effects of simvastatin in MCT-induced PH rats.

[Clinical features of pulmonary involvement in patients with microscopic polyangiitis].

OBJECTIVE: To explore the clinical features of pulmonary involvement in patients with microscopic polyangiitis (MPA). METHODS: We retrospectively investigated the clinical data of 50 patients hospitalized with MPA in Peking Union Medical College Hospital from January 2008 to December 2009, the data included clinical manifestation, laboratory parameters, echocardiography, pulmonary function test, chest computed tomography, and histopathology of kidney. RESULTS: Pulmonary involvements were observed in 46 patients, common symptoms include cough (34/46), expectoration (30/46), dyspnea (19/46) and hemoptysis (16/46). Pulmonary involvement was the initial manifestation in 14 patients, five cases had radiographic evidences of usual interstitial pneumonia before MPA was diagnosed. The prevalence of positive MPO-ANCA antibodies in MPA patients was 96%. The prevalence of positive PR3-ANCA antibodies was 6%. Radiographic manifestations included ground glass attenuation (16/37), interstitial changes (16/37), infiltrates (12/37) and pleural effusion (7/37). The most frequent abnormality in pulmonary function test was reduced carbon monoxide diffusing capacity (12/15) and restrictive ventilation dysfunction (4/15). The incidences of pulmonary hypertension was 33% (13/39), the average pulmonary artery systolic pressure was (48 ± 8) mm Hg (1 mm Hg = 0.133 kPa). CONCLUSION: The prevalence of pulmonary involvement in patients with MPA was high, pulmonary involvement was the initial manifestation in 28% patients. The clinical manifestations were nonspecific, radiographic manifestations included ground glass attenuation, interstitial changes, infiltrates and pleural effusion. The short term prognosis was well in patients with pulmonary involvement treated with systemic corticosteroids and cyclophosphamide, infection was a leading cause of death in patients with pulmonary involvement.

[Clinical analysis of acute pulmonary thromboembolism in 68 elderly patients].

OBJECTIVE: To explore the clinical characteristics of acute pulmonary thromboembolism (PTE) in elderly patients, in order to improve the diagnosis and treatment of the disease. METHOD: The clinical data were reviewed for patients aged over 60 years old hospitalized with acute PTE in Peking Union Medical College Hospital from January 2006 to January 2009. RESULTS: The average age of the 68 patients was (72 +/- 6) years old. Deep vein thromboembolism was found in 33 cases. Hypertension (55.9%), cancer (32.4%), surgery (29.4%), immobility (29.4%), diabetes (23.5%) and obesity (20.6%) were the most common risk factors, with 70.6% (48/68) of these patients having more than 2 risk factors. The common symptoms were dyspnea (77.9%), cough (26.5%), chest pain (13.2%), palpitation (13.2%), faint (13.2%) and asymmetric edema of the lower extremities (30.9%). All of the arterial blood gas in 61 cases showed hypoxemia. The positive rate of blood D-dimer elevation was 84% (47/56). The main signs in chest X-ray were infiltrates (37.5%) and pleural effusions (18.8%). Non-specific ST-T changes (59.3%) and sinus tachycardia (23.7%) were the most common abnormalities in electrocardiogram. Forty seven cases (69.1%) were diagnosed through CT pulmonary angiography (CTPA), and 20 cases (29.4%) were through ventilation-perfusion lung scintigraphy. Sixty one cases received anticoagulant therapy and 5 received thrombolytic therapy. Vena cava filters were implanted in 5 patients. Fifty six cases improved after treatment, and the case fatality ratio was 18% (12/68). CONCLUSION: The most common risk factors for PTE in elderly patients were chronic diseases, cancer, surgery and immobility. The symptoms and auxiliary examination of these patients were not specific, and CTPA was the most useful diagnosing tool. Anticoagulation was the basic treatment for PTE in elderly patients and it was safe and effective, while the overuse of thrombolytic therapy and vena cava filter should be avoided.

[Clinical analysis of 45 cases with pulmonary thromboembolism after surgical procedures].

OBJECTIVE: To analyze the occurrence of pulmonary thromboembolism (PTE) after surgical procedures to attract more attention to the prevention, diagnosis and treatment of this disease. METHODS: Retrospectively analyze the clinical data of the hospitalized patients with post-surgical PTE from June 2004 to February 2009. The average age of the 45 cases was (60 +/- 16) years old, 35 cases received anticoagulant therapy and 6 cases received thrombolytic therapy, the other 4 cases only received emergency medical treatment. Analyze the data about the surgery category, duration, anaesthetic way, risk factors, clinical symptoms, auxiliary examinations, diagnosis, treatment and turnover of these patients. RESULTS: Among the total 45 cases of post-surgical PTE, 37 cases (82.2%) occurred within 2 weeks, it accounted for 13.2% (45/341) of the hospitalized PTE patients during that period. PTE was often seen in patients after major surgical operation such as general (35.6%), gynecological (13.3%), orthopedic (13.3%) and chest surgery, especially the surgery related to malignant tumor (57.8%). The average surgical duration was (220 +/- 124) min, 37 cases (82.2%) was given general anaesthesia. The clinical manifestations and auxiliary examinations results of post-surgical PTE were not typical. Thirty-six cases improved after treatment, 9 cases died and the case fatality ratio was 20.0% (9/45). CONCLUSIONS: Surgical procedure is an important risk factor of PTE. The prevention diagnosis and treatment of post-surgical PTE should be paid more attention to.

[Pulmonary embolism in cancer: clinical analysis of 60 cases].

OBJECTIVE: To enhance the understanding of pulmonary thromboembolism (PTE) in patients with cancer. METHODS: from January 2005 to July 2008, sixty patients diagnosed as pulmonary thromboembolism in Peking Union Medical College Hospital were retrospectively reviewed. RESULTS: The primary cancers were from respiratory system (36.7%), digestive system (26.7%), urogenital system (10.0%), hematological system (8.3%) and nervous system (5.0%), respectively, especially from such organ as lung (30.0%), stomach (8.3%), pancreas (6.7%), liver (5.0%) and so on. 12 of 18 patients (66.7%) with lung cancer were adenocarcinoma. There were 47 patients (78.3%) with advanced cancer. Deep venous thrombosis (DVT) occurred in 30 patients (50.0%). Of them 24 patients (80.0%) occurred in the lower limb, and 3 patients (10%) in the upper limb, 5 patients (16.7%) in other sites including 2 cases with thrombi in both upper and lower limbs, respectively. There were 2 patients (3.3%) accompanied with femoral artery embolism. PTE before tumor diagnosed occurred in 5 patients (8.3%) with an average time of 5.5 months. 22 patients underwent cancer-related operation and 17 patients (77.3%) had PTE in the later 2 weeks. 15 patients (25.0%) showed no symptoms. Arterial oxygen partial pressure was reduced in 49 patients (84.5%). 13 patients (21.7%) died and 6 cases of them were sudden death. 8 patients (13.3%) aggravated. 39 patients (65.0%) improved. CONCLUSION: PTE is one of the major complications and leading causes of death in patients with cancer. Of which lung cancer is most commonly, pulmonary adenocarcinoma in particular. PTE is often accompanied by DVT in the lower extremity. Risk factors may be old age, cancer progression and cancer-related operation. Other factors include long time in bed, chemotherapy and central vein catheterization, and so on. It should be watchful of PTE in cancer patients undergoing operation, especially within the first two postoperative weeks. Its clinical manifestation is often atypical. Sometimes venous thromboembolism (VTE) is the first signal of malignancy. In patients with unexplained PTE and/or DVT, attention should be paid to the possibility of malignancy. The first choice of anticoagulants is low molecular weight heparin.

[Simvastatin prevents the development of pulmonary hypertension in the rats through reduction of inflammation].

OBJECTIVE: To investigate the protection of simvastatin on monocrotaline (MCT)-induce pulmonary hypertension (PH) and the mechanism thereof. METHODS: Thirty-two male Sprague-Dawley rats were randomly divided into 4 equal groups: PH group undergoing subcutaneous injection of MCT and then gastric infusion of normal saline (NS) once a day for 21 days, simvastatin control group undergoing subcutaneous injection of NS and then gastric infusion of simvastatin 2 microg/g once a day for 21 days, simvastatin intervention group undergoing subcutaneous injection of MTS and then gastric infusion of simvastatin 2 microg/g once a day for 21 days, and control group undergoing subcutaneous injection and gastric infusion of NS. Three weeks later the mean pulmonary arterial pressure (mPAP) was detected by right heart catheter. Then the rats were killed with their lungs taken out. Arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were calculated. Perivascular inflammation was scored with the subjective scale of 0 (no) to 4 (severe). Pulmonary interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), and monocyte chemotactic protein 1 (MCP-1) were tested by ELISA. RESULTS: The mPAP of the simvastatin intervention group was (23 +/- 7) mm Hg, significantly lower than that of the PH group [(34 +/- 9) mm Hg, P < 0.05], but not significantly different from that of the normal control group [(20 +/- 4) mm Hg, P > 0.05]. The W/V and T/D of the simvastatin intervention group were 0.442 +/- 0.061 and 0.325 +/- 0.045 respectively, significantly lower than those of the PH group (0.560 +/- 0.086 and 0.368 +/- 0.055 respectively, P < 0.01 and P < 0.05). The perivascular inflammation score of the simvastatin intervention group was (2.19 +/- 0.81), significantly lower than that of the PH group (3.40 +/- 0.65, P < 0.05), and the IL-6, TNF-alpha, and MCP-1 levels of the simvastatin intervention group [(264 +/- 127), (179 +/- 91), and (697 +/- 211) pg/ml respectively] were all significantly lower than those of the PH group [(765 +/- 179), (447 +/- 86), (4428 +/- 757) pg/ml respectively, all P < 0.01]. CONCLUSION: The protective effects of simvastatin against MCT-induced PH may be associated with the inhibition of the perivascular inflammation and lung IL-6, TNF-alpha, and MCP-1 levels.

[Study on changes of thrombi and vessel intima in a rat venous thromboembolism model].

OBJECTIVE: To observe the changes of thrombi and vessel intima in a rat model of venous thromboembolism (VTE). METHODS: Seventy-eight SD rats were randomly divided into deep vein thrombosis (DVT) group (n = 18), deep vein thrombosis-pulmonary thromboembolism (DVT-PTE) group (n = 54) and control group (n = 6). Rats in DVT and DVT-PTE groups were undergoing local blocking of left femoral artery with micro vessel clip to cause DVT. One, 4, and 7 days later 6 rats from DVT group were killed with their femoral veins observed by light and electron microscopy. Rats in DVT-PTE group underwent injection of the thrombi from left femoral vein solution in normal saline into the right femoral vein 1, 4, and 7 days after DVT formation to establish model of DVT-PTE. The 6 rats of each subgroup [D(n (1, 4, 7))P(n (1, 4, 7)) subgroups] were killed 1, 4, and 7 days after DVT-PTE formation respectively with their lungs observed by light and electron microscopy. RESULTS: (1) On day 1 after DVT, the successful rate of DVT was 100%. The positive thrombus rate in femoral veins on gross is lower on day 7 after DVT [42% (10/24)] than that on day 1 after DVT (chi(2) = 19.765, P < 0.01). The successful rates of DVT-PTE model were 100% (18/18), 83% (15/18), 44% (8/18) in the D(1)P(n), D(4)P(n) and D(7)P(n) subgroups respectively. The successful rate of DVT-PTE model is lower in the D(7)P(n) subgroups than that in the D(1)P(n) (chi(2) = 13.846, P < 0.01) and D(4)P(n) (chi(2) = 5.900, P < 0.05) subgroups. (2) One, 4, and 7 days after DVT, there were reddish, mixed, and organized thrombi in femoral veins. The thrombi in pulmonary arteries caused by the 4 or 7 days thrombi of DVT showed lower dissolubility than that from one day thrombi of DVT. The positive thrombus rate in pulmonary arteries on gross is higher in the D(4)P(n) and D(7)P(n) subgroups [73% (11/15) and 100% (8/8)] than that in the D(1)P(n) subgroups [39% (7/18, chi(2) = 3.915, P < 0.05; chi(2) = 8.474, P < 0.01)]. The ratio of vessel wall area and total vessel increased in D(1)P(7), D(4)P(4), D(7)P(4) and D(7)P(7) subgroups compared to the control group (P = 0.03, 0.00, 0.00, 0.011, respectively). (3) The junctures of femoral venous endothelial cells were ruptured and the intra-elastic layers were exposed on the 1(st) day, then the endothelial cells and intra-elastic layers became to disappear on the 7(th) day. The hyperplasia of pulmonary arterial intimal were observed on the 4(th) or the 7(th) day after the thrombi in pulmonary arteries caused by the 1 or 4 days thrombi of DVT. However, pulmonary arterial endothelial cells and intra-elastic layers maybe disappear on the 1(st) day after the thrombi in pulmonary arteries caused by the 7 days thrombi of DVT. CONCLUSIONS: The age and nature of thrombi before the embolization are related to the outcome of emboli and pulmonary arterial intimal alterations. For intimal, there are the changes of hyperplasia, intra-elastic layers thickening and even disappearance in femoral veins and pulmonary arteries after VTE.

[Establishment of rat model of venous thromboembolism].

OBJECTIVE: To establish a rat model of venous thromboembolism (VTE). METHODS: One hundred and forty-four SD rats were randomly divided into 2 equal groups: VTE-A group, undergoing local blocking of left femoral artery with micro vessel clip to cause deep vein thrombosis (DVT), and VTE-B group undergoing local blocking of left femoral artery with micro vessel clip in addition of administration of thrombin slowly injected from the distal end of the femoral vein blocked by micro clip. The rate of swelling limbs was observed. One, 4, and 7 days later 6 rats from each group were killed with their femoral veins taken out to observe the thrombosis rate by light microscopy. Other 18 rats in each group underwent injection of the thrombi from left femoral vein solution in normal saline into the right femoral vein 1, 4, and 7 days after DVT formation to establish model of DVT-pulmonary thromboembolism (PTE). The 6 rats of each group [VTE-A-D(n)P(n) and VTE-B-D(n)P(n) groups] were killed 1, 4, and 7 days after DVT-PTE formation respectively with their lungs taken out to observe the rate of PTE by light microscopy. RESULTS: (1) On day 1 after DVT, the successful rate of DVT was 100% in both VTE-A and VTE-B groups, and the swelling limb rate of the VTE-B group was 37.5% (27/72), significantly higher than that of the VTE-A group [16.7% (12/72), P = 0.005]. On day 7 after DVT, the positive thrombus rate of the VTE-B group was 83.3% (20/24), significantly higher than that of the VTE-A group [41.7% (10/24), P = 0.003]. One, 4, and 7 days after DVT, there were reddish, mixed, and organized thrombi in both VTE-A and VTE-B groups. (2) Tachypnea and tachycardia occurred immediately and disappeared spontaneously within 30 - 60 minutes when solution of thrombi was injected into pulmonary arteries via the right femoral veins. One rat died in the VTE-B-D(1)P(1) group 12 h after the embolization and was anatomically confirmed to suffer from fresh massive emboli lodged in pulmonary arteries. The successful rates of DVT-PTE model were 100% (18/18), 83.3% (15/18), and 44.4% (8/18) in the VTE-A-D(1)P(n), VTE-A-D(4)P(n), and VTE-A-D(7)P(n) groups respectively, and were 94.4% (17/18), 100% (18/18), and 83.3% (15/18) in the VTE-B-D(1)P(n), VTE-B-D(4)P(n), and VTE-B-D(7)P(n) groups respectively. The successful rate of DVT-PTE model in the VTE-B-D(7)P(n) group was higher than that in the VTE-A-D(7)P(n) group (P = 0.015). The thrombi in pulmonary arteries caused by the 4 or 7 days thrombi of DVT showed lower dissolubility in both VTE-A and VTE-B groups. CONCLUSIONS: A new rat model of VTE (DVT-PTE) has been successfully established. The successful rate of VTE can be increased when thrombin is slowly injected from the distal end of femoral vein blocked by micro clip in addition.

[Clinical manifestations and radiological features of hepatopulmonary syndrome.].

OBJECTIVE: To investigate the clinical and radiological features of hepatopulmonary syndrome (HPS). METHODS: Twenty two cases diagnosed as HPS in Peking Union Medical College Hospital from Nov, 1996 to Nov, 2008 were reviewed. Their clinical features and radiological findings were analyzed. RESULTS: The study included 12 males and 10 females with a mean age of (44 +/- 17) years and mean course of (54 +/- 52) months. Abnormalities on chest CT scans were found in 12 cases, which included intrapulmonary artery dilatation in 10 cases, with subpleural small nodular, reticular and patchy opacities; bilateral lower basal segmental artery dilatation in 3 cases; main pulmonary artery dilation in 1 case; right ventricular enlargement in 1 case and bilateral pleural effusion in 1 case. The chest CT was normal in 6 cases. CTPA and pulmonary artery angiogram were performed in 15 cases and artery dilatation was found in 4. Diffuse liver diseases were found in 12 cases by CT scans, 10 of them presented as typical hepatic cirrhosis and 2 cases as liver hepatomegaly, while esophagus varix and(or) fundus gastricus varix were found in 12 cases and splenomegaly in 6 cases, hydroperitonia in 3 cases. CONCLUSION: Clinical manifestations combined with CT features were helpful for the diagnosis of HPS.

[The low molecular weight heparin on rat pulmonary surfactant associated protein A of acute pulmonary embolism].

OBJECTIVE: To explore the effect of low molecular weight heparin (LMWH) on the changes of pulmonary surfactant associated protein A (SPA) of rats in acute pulmonary embolism. METHODS: Male SD rats were injected with medical gelfoam microspheres via jugular vein to induce PE model. Rats were randomized into three groups: control group (n = 8), embolism for 2 weeks group (n = 8) and LMWH therapy group (n = 8); The LMWH therapy group were injected Nadroparin subcutaneously immediately after operation, 0.1 ml/10 kg, once every 12 h. Saline were injected into the control group instead of gelfoam granule solution without further procedure. All the rats were sacrificed at the time of 2 weeks. Pulmonary artery pressure were detected by right heart catheterization and artery blood gas were analyzed at the time of sacrifice. Lung tissue were sliced and dyed with HE to observe the embolism of pulmonary artery. Methods of RT-PCR and western blot were used to study the changes of SPA mRNA and SPA protein in lung tissue. RESULTS: In control group, embolism group and LMWH group, the pulmonary pressure were (14.2 +/- 4.1) mm Hg, (29.0 +/- 8.2) mm Hg, (25.50 +/- 2.74) mm Hg respectively (F3.01, P < 0.05); the artery oxygen blood pressure (PaO2) were (94.1 +/- 8.8) mm Hg, (73.4 +/- 14.3) mm Hg, (82.86 +/- 3.73) mm Hg respectively (F 1.31, P < 0.05); SPA mRNA in three groups were 1.43 +/- 0.51, 0.87 +/- 0.35, 1.07 +/- 0.20 respectively (F 2.87, P < 0.05); and SPA protein were 1.00 +/- 0.00, 0.52 +/- 0.32, 0.90 +/- 0.22 respectively (F 2.96, P < 0.05); Under microscope, lung tissue were seen congestion, edema, infiltration of inflammatory cells in embolism group, which were lessened in LMWH group. CONCLUSIONS: The lung SPA decrease significantly in acute pulmonary embolism, and LMWH can increase the SPA, which may be one of mechanisms of LMWH in treatment of pulmonary embolism.

[Analysis of the treatment and prognosis of 59 patients with sarcoidosis].

OBJECTIVE: To investigate the relationship between clinical characteristics, treatment and prognosis of sarcoidosis, and to analyze the factors for disease severity and prognosis. METHOD: Retrospective analysis of 59 patients with sarcoidosis admitted to Peking Union Medical College Hospital from January 1984 to January 2003, with a follow-up for at least 24 months. RESULTS: The mean follow-up period was (61.9 +/- 49.4) months. All of the 7 patients with stage 0 accepted glucocorticoid therapy and responded well, and 4 of them completely remitted. Among 22 cases with stage I disease, 4 underwent spontaneous remission while another one who had extra-pulmonary sarcoidosis at the onset progressed after follow-up for 6 months. Seventeen cases were treated with glucocorticoids after the diagnosis was confirmed. Before this study, 9 patients had experienced complete remission, and 7 had been stable disease respectively, while one had progressed to stage II. Twenty-two of the 23 stage II patients received glucocorticoids initially and one was treated after an observation period of 3 months before deterioration. Thirteen patients of stage II were completely cured, and 2 were still progressing under the drug therapy. All of the 5 patients in stage III accepted glucocorticoids after diagnosis. One of the 5 patients has resolved completely and 2 had progressed into stage IV. The interstitial changes of the lung in 2 stage IV patients had been progressing even though the treatment lasted for years. There were no significant differences in the serum angiotensin converting enzyme (ACE) level, total broncho-alveolar fluid (BALF) cell count, percentage of alveolar lymphocytes, neutrophils and lymphocyte CD(4)/CD(8) ratio at the onset between stage I and stage II diseases. Age, gender, presence of respiratory symptom, serum ACE level, total BALF cell count, percentage of alveolar lymphocytes, neutrophils or lymphocyte CD(4)/CD(8) ratio at the onset were not associated with relapse. 14 cases relapsing pulmonary sarcoidosis had extra-pulmonary lesions, and there was a close correlation between the relapse and extra-pulmonary lesions (P = 0.006). A significant increase in the percentage of BALF neutrophils (8.37 +/- 3.55)% at the time of diagnosis was observed in patients who had not completely resolved as compare with the patients who had recovered [(3.52 +/- 2.37)%, P < 0.001]. CONCLUSION: The outcome of sarcoidosis are generally good. Patients with extra-pulmonary sarcoidosis are more likely to experience relapse. Stage I disease should receive observation before glucocorticoid therapy. Increased percentage of neutrophils in BALF at the onset is possibly associated with a progressive or persistent disease.

[The clinical analysis of pulmonary arterial hypertension in connective tissue disease].

OBJECTIVE: To investigate the clinical features and prognosis of pulmonary arterial hypertension (PAH) secondary to connective tissue disease (CTD). METHODS: Eighty-two patients diagnosed as having CTD associated PAH (CTDaPAH) were retrospectively analyzed among 2189 patients with CTD in Peking Union Medical College Hospital between January 1997 and September 2004. RESULTS: Eighty-two (3.7%) patients (75 females and 7 males), aged 41 years, were found to have CTDaPAH. The underlying diseases included mixed CTD (MCTD), systemic scleroderma, primary Sjogren's syndrome (pSS), systemic lupus erythematosus (SLE), undifferentiated CTD, dermatomyositis and Behcet disease. PAH was an earlier complication in patients with SLE or MCTD (median onset, 3 and 2 years, respectively), compared to those with pSS (6 years). The most common clinical manifestations of CTDaPAH were dyspnea on exertion (84.1%) and Raynaud's phenomenon (56.1%). The mean pulmonary artery systolic pressure (PASP) level of these patients was (65.71 +/- 20.44) mm Hg, with the decrease of PaO2 and PaCO2 level [(70.37 +/- 15.02) mm Hg, (27.88 +/- 6.46) mm Hg, respectively]. The diffusing capacity of the lungs measured using carbon monoxide was decreased [D(L)CO pred% (51 +/- 14)%]. 13%, 32%, 29% and 8% of these patients were grouped to class I, II, III and IV, respectively, on NYHA functional classification. Although the patients received treatment for underlying CTD and traditional vasodilators, the condition of elevated PASP had not been improved with the exception of a marginal decrease of PASP in SLE patients [(76.47 +/- 18.20) mm Hg --> (69.08 +/- 20.77) mm Hg]. Thirteen (15.85%) patients died during an average of 4.33 years follow-up, compared to the mortality of those with non-CTDaPAH (2.75%, P < 0.01). Lower level of PaO2 [(58.51 +/- 16.16) mm Hg] and higher proportion of NYHA class III, IV [38.46% (5/13), 30.77% (4/13), respectively] were observed in death group compared to survivors [PaO2 (73.25 +/- 14.32) mm Hg; NYHA class III, IV 34.78% (24/69), 5.80% (4/69), respectively] (P < 0.01; P < 0.05; respectively). CONCLUSIONS: PAH is a common complication of CTDs, which occurs often in the forth year after initial CTD manifestations and is earlier in patients with SLE or MCTD, compared to those with pSS. The most common manifestations of CTDaPAH are dyspnea on exertion and Raynaud's phenomenon. CTDaPAH could be very severe, which will lead to lower level of PaO2 and more advanced NYHA classification, and therefore reduce the survival rate of the patients. Doppler echocardiography and lung function test are necessary to detect PAH early.

[Clinical analysis of 23 cases of hepatopulmonary syndrome].

OBJECTIVE: To describe the clinical features and to highlight the main criteria for diagnosis of hepatopulmonary syndrome (HPS). METHODS: Twenty-three patients with HPS were retrospectively investigated. RESULTS: Twenty-two cases had cirrhosis while one had acute hepatitis. The male to female ratio was 1.3:1, with an mean age of (42 +/- 21) years. 82.6% (19/23) of the patients were complicated with portal hypertension. The liver function of 78.2% of the cases was Child-Pugh grade B and C. The main clinical manifestations were dyspnea (91.3%), cyanosis (91.3%), liver palms (69.5%), clubbing fingers (65.1%), telangiectasis on face (56.5%), and spider angiomata (56.5%). The mean PaO(2) was (50.8 +/- 14.1) mm Hg (1 mm Hg = 0.133 kPa). Incidence of orthodeoxia was 85.7% (12/14). Mean diffusing capacity of lung function test was 43.1%. Chest X-ray was abnormal in 9 of the 39.1 (9/23) patients. Faint "mottled" shadows, nodular or reticulonodular opacities on bilateral lower zones were shown. All the 23 cases were diagnosed by radionuclide lung perfusion scanning technetium-labled macroaggregated albumin particles ((99m)Tc-MAA) and the mean shunt ratio was 36.3%. CONCLUSION: HPS is often associated with advanced Child-Pugh grade or portal hypertension. When "unexplained" hypoxaemia, portal hypertension, spider angiomata (or telangiectasis on face), or clubbing finger are present in these patients, HPS should be highly suspected. The presence of orthodeoxia is suggestive of HPS. (99m)Tc-MAA lung perfusion scanning is able to determine the presence of intrapulmonary shunting and the diagnosis of HPS.