Objective To observe the correlations of chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)with blood eosinophil(EOS)level.Methods Chest CT data of 16...Objective To observe the correlations of chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)with blood eosinophil(EOS)level.Methods Chest CT data of 162 AECOPD patients with elevated eosinophils were retrospectively analyzed.The patients were divided into low EOS group(n=105)and high EOS group(n=57)according to the absolute counting of blood EOS.The quantitative CT parameters,including the number of whole lung bronchi and the volume of blood vessels,low-attenuation area percentage(LAA%)of whole lung,of left/right lung and each lobe of lung,as well as the luminal diameter(LD),wall thickness(WT),wall area(WA)and WA percentage of total bronchial cross-section(WA%)of grade 3 to 8 bronchi were compared between groups.Spearman correlations were performed to analyze the correlations of quantitative CT parameters with blood EOS level.Results LAA%of the whole lung,of the left/right lung and each lobe of lung,as well as of the upper lobe of right lung LD grade 4,middle lobe of right lung WT grade 5,upper lobe of right lung WA grade 4,middle lobe of right lung WA grade 5 and lower lobe of left lung WA grade 3 in low EOS group were all higher than those in high EOS group(all P<0.05).Except for the upper lobe of right lung LD grade 4,the above quantitative CT indexes being significant different between groups were all weakly and negatively correlated with blood EOS level(r=-0.335 to-0.164,all P<0.05).Conclusion Chest CT quantitative parameters of AECOPD patients were correlated with blood EOS level,among which LAA%,a part of WT and WA were all weakly negatively correlated with blood EOS level.展开更多
Objective To evaluate the effect of the cardiopulmonary bypass (CPB) on the pulmonary function in infants with or withoutpulmonary hypertension in congential ventricular septal defect (VSD). MethodsTwenty infants with...Objective To evaluate the effect of the cardiopulmonary bypass (CPB) on the pulmonary function in infants with or withoutpulmonary hypertension in congential ventricular septal defect (VSD). MethodsTwenty infants with VSD were enrolled in the study fromJan. to Dec.2004. They were divided into two groups: pulmonary hypertension group and non-pulmonary hypertension group, ten infantsrespectively. Pulmonary function parameters were measured before CPB and 3, 6, 9, 12, 15, 18, 21, 24h after CPB, the following datawere recorded: duration for mechanical ventilation (Tmv) and staying in the cardiac intensive care unit (Tcicu) after cardiac surgery.Results Before CPB, the pulmonary function parameters in non-pulmonary hypertension group were more superior than in pulmonary hy-pertension group (P<0.01). By contraries, the pulmonary function parameters in every time stage after CPB statistically significant de-creased in non-pulmonary hypertension group (P<0.05), especially at 6, 9, and 15h after CPB (P<0.01). In pulmonary hyperten-sion group, the pulmonary function parameters in 3h after CPB were more improved than before CPB, though there was no statistical sig-nificance. But they had statistically significant decreased at9, 12, 15h after CPB (P<0.05). There was a similar change in pulmonaryfunction between two groups at 21, 24h after CPB. Conclusion Exposure to CPB adversely affects pulmonary function after surgicalrepair of VSD in infants. We consider that the benefits of the surgical correction in infants with pulmonary hypertension outweight the neg-ative effects of CPB on pulmonary function. We should improve cardiac function to avoid the presence of the nadir trough in pulmonaryfunction. The infants with pulomonary hypertension also have ability to wean from mechanical ventilation as soon as possible, if the hemo-dynamics is stable, and without the responsive pulmonary hypertension or pulmonary hypertension crisis after surgical repair.展开更多
OBJECTIVE To explore the role of calpain in in pulmonary vascular remodeling in hypoxia induced pulmonary hypertension and the underlying mechanism.METHODS Sprague-Dawley rats were randomly divided into hypoxia group ...OBJECTIVE To explore the role of calpain in in pulmonary vascular remodeling in hypoxia induced pulmonary hypertension and the underlying mechanism.METHODS Sprague-Dawley rats were randomly divided into hypoxia group and normoxia control group.Right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(m PAP)were monitored by the method of right external jugular vein cannula.Right ventricular hypertrophy index was expressed as the ratio of right ventricular weight to left ventricular weight(left ventricle plus septum weight).Level of calpain-1,calpain-2and calpain-4 m RNA in pulmonary artery trunk were determined by real-time PCR.Expression of calpain-1,calpain-2 and calpain-4 protein was determined by Western Blot.Primary rat pulmonary arterial smooth muscle cells(PASMCs)were divided into 4 groups:normoxia control group,normoxia+MDL28170 group,hypoxia group and hypoxia+MDL28170 group.Cell proliferation was detected by MTS and flow cytometry.Level of Ki-67 and PCNA m RNA were determined by real-time PCR.RESULTS RVSP,m PAP and right ventricular remodeling index were significantly higher in the hypoxia group than those in the normoxia group.In the hypoxia group,pulmonary vascular remodeling occurred,and the expression of calpain-1,calpain-2 and calpain-4 m RNA and protein expression was increased in the pulmonary artery.MDL28170 significantly inhibited hypoxia-induced proliferation of PASMCs accompanied with decreased Ki-67and PCNA m RNA expression.CONCLUSION Calpain mediated vascular remodeling via promoting proliferation of PASMCs in hypoxia induced pulmonary hypertension.展开更多
OBJECTIVE Pulmonary artery hypertension(PAH)is a severe disease characterized by the mean pulmonary artery pressure exceeding 25 mm Hg at rest.PAH could induce right heart failure and has a very high mortality rate.At...OBJECTIVE Pulmonary artery hypertension(PAH)is a severe disease characterized by the mean pulmonary artery pressure exceeding 25 mm Hg at rest.PAH could induce right heart failure and has a very high mortality rate.At present,several kinds of drugs have been used in the treatment of PAH.However,most of these drugs aim to relax pulmonary arteries and do not inhibit the injury of vessels.In other words,the drugs available for PAH treatment do not improve the survival rate of PAH patients and cannot satisfy the needs in clinic.To discover and develop novel candidate compounds effective on the treatment of pulmonary artery injury and remodeling will be very important.Based on these background,the present study aimed to study the protective effect of two novel Rho-kinases(Rho-associated coiledcoil forming protein serine/threonine kinase,ROCK)inhibitors,DL0805 derivatives(DL0805-1and DL0805-2),on pulmonary arterial cells and further evaluate the underlying mechanisms and the possibility of DL0805 derivatives become therapeutic drugs for PAH.METHODS The primary cultured pulmonary arterial cells including human pulmonary artery endothelium cells(HPAECs)and human pulmonary artery smooth muscle cells(HPASMCs)were used in this study.HPAECs were injured under hypoxia environment(1%O2)and treated with or without DL0805 derivatives.After 48 h,the proliferation and oxidative stress were observed.CCK8 was used to detect cell viability.DCFH-DA was used as probe for reactive oxygen species(ROS)under fluorescence imaging system.HPASMCs was stimulated by growth factors including platelet-derived growth factor-BB(PDGF-BB)and Fetal Bovine Serum(FBS).The proliferation was observed in the cells treated with or without DL0805 derivatives.HPASMCs treated with or without DL0805 derivatives were further incubated with endothelin(ET-1),the proliferation and cytoskeleton remodeling of cells were detected by immunofluorescence assay.At last,Western blotting(WB)and immunofluorescence assay were employed to analysis the underlying mechanisms in the above experiments.RESULTS 10μmol·L-1DL0805-2 could inhibit the proliferation of HPAECs induced by hypoxia.Each concentration of DL0805-1 and DL0805-2attenuated the production of ROS in HPAECs.Results from WB indicated that DL0805 derivatives decreased the injury of HPAECs induced by hypoxia through the inhibition of the expression of Rho A and the activity of ROCK.On HPASMCs,DL0805 derivatives reduced the proliferation induced by PDGF-BB and FBS and inhibited cytoskeleton remodeling induced by ET-1.Immunofluorescence assay showed that DL0805 derivatives inhibited ROCK activity and down regulated the phosphorylation levels of ROCK substrates.CONCLUSION DL0805derivatives exhibited protective effect on pulmonary arterial cells including endothelium cells and smooth muscle cells.Among the above experiments,DL0805-2 showed stronger potency than DL0805-1.These two compounds might protect the cells through the inhibition of Rho A/ROCK pathway and they probably have the potential in the treatment of PAH and deserve further evaluation.展开更多
Objective Cardiopulmonary exercise testing(CPET)is helpful to identify right ventriclar(RV)dysfunction in patients with rapair of Tetralogy of Fallot(rTOF),but its predictive value on early outcomes of pulmonary valve...Objective Cardiopulmonary exercise testing(CPET)is helpful to identify right ventriclar(RV)dysfunction in patients with rapair of Tetralogy of Fallot(rTOF),but its predictive value on early outcomes of pulmonary valve replacement(PVR)of these patients is unclear when similar preoperative ventricular size and function in cardiovascular magnetic resonance(CMR)exist.The aim of this study is to evaluate whether CPET is useful to predict the early outcomes of rTOF patients after PVR.展开更多
Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregul...Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregulated in the lung tissue of CHD-PAH patients,especially in the irreversible group.However,how exactly it participated in CHD-PAH development is unknown.展开更多
OBJECTIVE Leukotriene B4(LTB4)biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury(ALI)or idiopathic pulmonary fibrosis(IPF).To provide a pote...OBJECTIVE Leukotriene B4(LTB4)biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury(ALI)or idiopathic pulmonary fibrosis(IPF).To provide a potential strategy for the treatment of ALI or IPF,we identified potent inhibitors of Leukotriene A4 hydrolase(LTA4H),a key enzyme in the biosynthesis of LTB4.METHODS In this study,we identified two known histone deacetylase(HDAC)inhibitors,suberanilohydroxamic acid(SAHA)and its analogue 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide(M344),as effective inhibitors of LTA4H using enzymatic assay,thermofluor assay,and X-ray crystallographic investigation.We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay.A murine experimental model of ALI was induced by lipopolysaccharide(LPS)inhalation.Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA.We next examined m RNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using q RT-PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA.We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin(BLM)-induced IPF model.RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H,significantly decrease LTB4 levels in neutrophil,and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose.CONCLUSION Collectively,SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.展开更多
Background and Objective Pulmonary hypertension (PH) is a fatal disease resulting from various causes. Studies from abroad have shown iron deficiency (ID) is closely associated with disease progression.This associatio...Background and Objective Pulmonary hypertension (PH) is a fatal disease resulting from various causes. Studies from abroad have shown iron deficiency (ID) is closely associated with disease progression.This association is common in pulmonary arterial hypertension (PAH)that belongs to World Health Organization group 1 PH. However, ID prevalence in Chinese patients suffering from PH is unclear so far.展开更多
Background Tetralogy of Fallot(TOF)is the most common cyanotic heart defect,accounting for 10%of all congenital defects.Pulmonary valve stenosis(PVS)is one common right ventricular outflow tract obstruction problem in...Background Tetralogy of Fallot(TOF)is the most common cyanotic heart defect,accounting for 10%of all congenital defects.Pulmonary valve stenosis(PVS)is one common right ventricular outflow tract obstruction problem in patients with TOF.Congenital bicuspid pulmonary valve(BPV)is a condition of valvular stenosis,which morphologic feature is the presence of only two pulmonary leaflets instead of the normal tri-leaflet.Congenitally BPV are uncommon and the occurrence is often associated with TOF.Methods The three-dimensional geometric reconstruction of pulmonary root(PR)were based on well-accepted mathematical analytic models with physiological parameters obtained from a typical sample of the pulmonary root used in clinical surgery.The PR geometry included valvular leaflets,sinuses,interleaflet triangles and annulus.The dynamic computational models of normal PR with tri-leaflet and PR with BPV in patients with TOF were developed to investigate the effect of geometric structure of BPV on valve stress and strain distributions and the geometric orifice area.Mechanical properties of pulmonary valve leaflet were obtained from biaxial testing of human pulmonary valve left leaflet,and characterized by an anisotropic Mooney-Rivlin model.The complete cardiac cycle was simulated to observe valve leaflet dynamic stress and strain behaviors.Results Our results indicated that stress/strain distribution patterns of normal tri-leaflet pulmonary valve(TPV)and the BPV were different on valve leaflets when the valve was fully open,but they were similar when valves were completely closed.When the valve was fully open,the BPV maximum stress value on the leaflets was 218.1 kPa,which was 128.0%higher than of the normal TPV value(95.6 kPa),and BPV maximum strain value on the leaflets was 70.7%higher than of the normal TPV.The location of the maximum stress from TPV and BPV were also different,which were found at the bottom of the valve near the leaflet attachment for TPV and the vicinity of cusp of the fusion of two leaflets for BPV,respectively.During the valve was fully open,the stress distribution in the interleaflet triangles region of the PR was more asymmetric in the BPV model compared with that in the normal TPV model,and the largest change on the PR with the geometrical variations in the two models was 39.6%in maximum stress.This stress asymmetry indicates that BPV may be one of the causes of post-stenotic pulmonary artery dilatation and aneurysm in patients with TOF.The cusp of the BPV model showed significant eccentricity during peak systolic period,and its geometric orifice area value in the completely opened position of valve was reduced 57.5%from that of the normal TPV model.Conclusions Our initial results demonstrated that valve geometrical variations with BPV may be a potential risk factor linked to occurrence of PVS in patients with TOF.Computational models could be used as an effective tool to identifying possible linkage between pulmonary valve malformation disease development and biomechanical factors,better design of artificial valves and new surgical procedures without testing those on patients.Large-scale clinical studies are needed to validate these preliminary findings.展开更多
Aim Rhodiola rosea L. possesses a wide range of pharmacological properties including lung-protective, and it has been implemented in folk medicine for several 100 years. However, the accurate mechanisms of its lung- p...Aim Rhodiola rosea L. possesses a wide range of pharmacological properties including lung-protective, and it has been implemented in folk medicine for several 100 years. However, the accurate mechanisms of its lung- protective activity remain unclear. This study aimed at investigating the possible mechanisms of lung-protective activity of Rhodiola rosea L. in pulmonary fibrosis model. Methods Pathological observation, ROS detection and measure- ments of biochemical indexes on rat models proved lung-protective effect of Rhodiola rosea L. Identification of active compounds in Rhodiola rosea L. was executed through several methods including UPLC-TOF-MS. SEA docking, too- lecular modeling, molecular docking, and molecular dynamics （MD） simulation were applied in this study to explore possible mechanisms of the lung-protective potential of Rhodiola rosea L. Furthermore, in vitro cytological examina- tion and Western blot were used for validating the efficacy of the selected compounds. Results Experiments on rat models showed a potent lung-protective effect of Rhodiola rosea L. Then we analyzed the chemical composition of Rhodiola rosea L. and found out their key targets. Moreover, in silico analysis results testified good interaction be- tween selected compound 13 and key targets Akt-1/Caspase-1, and compound 10 also interacts well with Akt-1. Fur- ther Western blot analysis proved changed expression levels of those target proteins, indicating that selected small compounds indeed acted on those targets. Conclusion In silico analysis and experimental validation together demon- strated that selected compound 10 in Rhodiola rosea L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both Caspase-1 and Akt-1. These small compounds may ameliorate pulmonary fibrosis by acting on their targets which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Rhodiola rosea L. acting on pneumonocyte and ameliorating pulmonary fibrosis.展开更多
Aim To investigate the effects of general ginsenoside on the pulmonary fibrosis in mice. Methods All the animals were divided into the sham operation group, model control group and the groups administered with gen- er...Aim To investigate the effects of general ginsenoside on the pulmonary fibrosis in mice. Methods All the animals were divided into the sham operation group, model control group and the groups administered with gen- eral ginsenoside （40, 80, 160 mg · kg^-1） and prednisone （5 mg · kg^-1） group. The mice pulmonary fibrosis was induced by bleomycin （BLM 5 mg · kg^-1） and general ginsenoside （40, 80 and 160 mg · kg^-1） and prednisone （ 5 mg · kg^- 1 ） were given the day after surgery for 28consecutive days. The pulmonary fibrosis induced by bleomy- cin （BLM 5 mg · kg^-1） was evidenced by the pulmonary index, histopathology, and by the expression of alpha smooth muscle actin （oL-SMA）. Results Compared with that of the sham operation control, the pulmonary index were remarkably increased, Pathological examination demonstrated that BLM administration induced focal fibrotie lesions （ Alveolitis and pulmonary fibrosis） in mice lungs, and the expression of α-SMA mRNA was elevated for sev- eral time in the model control. However, compared with model control, general ginsenoside and prednisone admin- istrated could cause significantly decreases in the pulmonary index, the degree and extent of alveolitis and fibrosis had different degree of ease, reduce the elevated α-SMA mRNA expression. Conclusion General ginsenoside in- duced protection against the pulmonary fibrosis induced by bleomycin in mice.展开更多
Objective To summarize the clinical characteristics and the effect of pulmonary endarterectomy(PEA)in CTEPH patients with unilateral main pulmonary artery occlusion.Methods Of 160 CTEPH patients operated between Janua...Objective To summarize the clinical characteristics and the effect of pulmonary endarterectomy(PEA)in CTEPH patients with unilateral main pulmonary artery occlusion.Methods Of 160 CTEPH patients operated between January2004 and March 2018 at our center,13(8.1%)had complete main pulmonary artery occlusion.Patients were included if the ventilation/perfusion(V/Q)scan revealed nonperfusion of an entire lung and the pathological examination showed chronic thromboembolic.展开更多
Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hyp...Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hypertension （PAH） and discuss the underlying mechanisms preliminarily. Methods A classical PAH animal model was used, which was established by single injection of 50 mg · kg^-1 monocrotaline （MCT）. One week later, the rats were administrated with 1, 3, 10 mg · kg^-1 DL0805-2 via intraperitoneal injection for 18 days. At the end of the experiment, the body weight and survival rate were recorded. Meanwhile, the respiration function, heart function, blood pressure and pulmonary artery pressure were detected. Serum was collected for biochemical index analysis. The weight of vital organs was used to calculate the organ index. Histopathology examination was em-ployed to observe the subtle changes in hearts, vessels and lungs. Furthermore, the mechanisms were studied main- ly by the method of western blotting. Results DL0805-2 did not show significant influence on body weight of PAH rats. But the survival rate of PAH rats treated with 3 and 10 mg · kg^-1 DL0805-2 was increased up to 90. 9% com- pared with the model group （68.2%）. DL0805-2 improved the pulmonary artery blood flow especially the maximal -1 -1 velocity （PV max） from 397.2 cm · s^-1 to 506.5, 540. 1 and 574.0 cm · s^-1 respectively. The results of echocar- diography and electrocardiogram show that DL0805-2 had little effect on left ventricle and systemic circulation but attenuated right ventricle injury and decreased the right ventricle pressure from 73.73 mmHg to 47.80, 42.64 and 46.45 mmHg respectively after DL0805-2 intervention. Disease markers of PAH including NT-proBNP in serum and ET-1 in lung tissue homogenate and serum biochemical indicators, ALT, AST and LDH, were reduced by DL0805-2. DL0805-2 also relieved edema of lungs and decreased inflammatory cytokines production. Through the examination on histopathologic slide of pulmonary main artery, right ventricle and lung, DL0805 derivatives were found to have significant protection effect on structural changes of organs induced by pulmonary hypertension. Ac- cording to the preliminary study on the mechanisms of DL0805-2 in PAH, Rho/ROCK pathway was significantly in- hibited by DL0805 derivatives. In addition, DL0805 derivatives showed effect on BMPRII/p-Smad pathway and ap- optosis related pathway. Conclusion DL0805-2 has showed potent treatment effect on the PAH rats. And the un- derlying mechanisms studies also indicated that RhoA/ROCK and BMPRII pathways were involved. This work will provide basis experimental data for the further research and development of DL0805-2.展开更多
Hemodynamic responses to hypoxic challenge on rats werechecked either in anesthetic state or in awake state. The rats in awake state wereunder taken hemodynamic study at 48 hours after Pentobarbital（PB） anesthesiaan...Hemodynamic responses to hypoxic challenge on rats werechecked either in anesthetic state or in awake state. The rats in awake state wereunder taken hemodynamic study at 48 hours after Pentobarbital（PB） anesthesiaand catheterization. Hemodynamic responses to hypoxic ventilation on dogs wasconducted either at 2 hours or at 4 hours after PB. During hypoxic ventilationflaxidel was used to maintain skeletal muscular relaxation, yet PB was not re-peated to diminish it’s influence on hypoxic responses. Blood gas assay was car-ried out in dogs during normoxia and hypoxic challenge. Hypoxic challengecaused significant increase of pulmonary artery pressure （Ppa） and almost nochange in systemic artery pressure （Psa） in awake rats. However in anestheticrats hypoxic challenge had little effect on Ppa, without influence on Psa. At 2and 4 hours after PB administration and catheterization hypoxic ventilationcaused similar change in blood gas （PaO<sub>2</sub> and PvO<sub>2</sub>）. However the second hy-poxic ventilation （4h） produced more significant pulmonary hemodynamic re-sponses （Ppa and TPVR greatly increased）. These results suggested thatpreferable acute hypoxic pulmonary hypertension developed either in awake ratsor in relatively shallow anesthetic state of dogs, indicating that PB anesthesiamay inhibit hypoxic pulmonary hemodynamic responses.展开更多
OBJECTIVE The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling,which is characteristic of pulmonary arterial hypertension(PAH).In this study we exam-ined whether s...OBJECTIVE The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling,which is characteristic of pulmonary arterial hypertension(PAH).In this study we exam-ined whether salvianolic acid A(SAA)extracted from the traditional Chinese medicine′Dan Shen′attenuated vascular remodeling in a PAH rat model,and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline(MCT 60 mg·kg-1,sc).The rats were orally treated with either SAA(0.3,1,3 mg·kg-1·d-1)or a positive control bosentan(30 mg·kg-1·d-1)for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA or bosentan effectively ameliorated MCTinduced pulmonary artery remodeling,pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure(RVSP).Furthermore,the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal injury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphogenetic protein typeⅡreceptor(BMPRⅡ)and phosphorylated Smad1/5 in the lungs.CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRⅡ-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the patients at high risk of PAH.展开更多
Background and Objective Ablation within the pulmonary sinus of Valsalva (PSV) becomes increasingly common in certain ventricular outflow arrhythmia. Understanding the regional anatomy is intensively concerned to avoi...Background and Objective Ablation within the pulmonary sinus of Valsalva (PSV) becomes increasingly common in certain ventricular outflow arrhythmia. Understanding the regional anatomy is intensively concerned to avoid procedure complications. The purpose of this study is to describe the anatomic relationships of PSV to its adjacent structures using computed tomographic coronary angiograms (CTCA).展开更多
Objective Hypoxemia is one of the main factors of pulmonary hypertension,and it can also be a complication of pulmonary hypertension,and it is a risk factor for many cardiovascular diseases,which increases the adverse...Objective Hypoxemia is one of the main factors of pulmonary hypertension,and it can also be a complication of pulmonary hypertension,and it is a risk factor for many cardiovascular diseases,which increases the adverse prognosis of patients.At present,there are some controversies about the diagnosis and treatment of sleep apnea disorder in patients with pulmonary hypertension.展开更多
Objective To analyze the clinical features and effects of target therapy of post splenectomy pulmonary hypertension, and improve the diagnosis and treatment of the disease.Methods Clinical data of 18 patients with pos...Objective To analyze the clinical features and effects of target therapy of post splenectomy pulmonary hypertension, and improve the diagnosis and treatment of the disease.Methods Clinical data of 18 patients with post splenectomy pulmonary hypertension admitted to our hospital from October 2006 to March 2017 were systematically reviewed.展开更多
Objective To investigate the risk factors associated with combined post-capillary and pre-capillary pulmonary hypertension(Cpc-PH)and the prognostic difference between isolated post-capillary pulmonary hypertension(Ip...Objective To investigate the risk factors associated with combined post-capillary and pre-capillary pulmonary hypertension(Cpc-PH)and the prognostic difference between isolated post-capillary pulmonary hypertension(Ipc-PH)and Cpc-PH in pulmonary hypertension due to left heart failure.Methods From October 2012 to November 2016,patients with pulmonary hypertension due to heart failure with preserved ejection fraction(PH-HFpEF)and pulmonary hypertension due to heart failure with reduced ejection fraction(PH-HFrEF)were prospectively enrolled from 11 centers all over the country.展开更多
Background and Purpose Recent studies found endothelialto-mesenchymal transition(EndoMT)played an important role in the pathogenesis of pulmonary arterial hypertension.Our pilot research demonstrated the existence of ...Background and Purpose Recent studies found endothelialto-mesenchymal transition(EndoMT)played an important role in the pathogenesis of pulmonary arterial hypertension.Our pilot research demonstrated the existence of Warburg effect in the lung tissue of idiopathic pulmonary arterial hypertension patients.However the relationships and the underlying mechanisms between EndoMT and Warburg effect have not been elucidated.Therefore,the purpose of this study is to determine whether metabolic reprogramming happens in EndoMT cells.We also want to investigate whether sodium dichloroacetate(DCA),a metabolic modulator,could prevent EndoMT by inhibiting Warburg effect.展开更多
文摘Objective To observe the correlations of chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)with blood eosinophil(EOS)level.Methods Chest CT data of 162 AECOPD patients with elevated eosinophils were retrospectively analyzed.The patients were divided into low EOS group(n=105)and high EOS group(n=57)according to the absolute counting of blood EOS.The quantitative CT parameters,including the number of whole lung bronchi and the volume of blood vessels,low-attenuation area percentage(LAA%)of whole lung,of left/right lung and each lobe of lung,as well as the luminal diameter(LD),wall thickness(WT),wall area(WA)and WA percentage of total bronchial cross-section(WA%)of grade 3 to 8 bronchi were compared between groups.Spearman correlations were performed to analyze the correlations of quantitative CT parameters with blood EOS level.Results LAA%of the whole lung,of the left/right lung and each lobe of lung,as well as of the upper lobe of right lung LD grade 4,middle lobe of right lung WT grade 5,upper lobe of right lung WA grade 4,middle lobe of right lung WA grade 5 and lower lobe of left lung WA grade 3 in low EOS group were all higher than those in high EOS group(all P<0.05).Except for the upper lobe of right lung LD grade 4,the above quantitative CT indexes being significant different between groups were all weakly and negatively correlated with blood EOS level(r=-0.335 to-0.164,all P<0.05).Conclusion Chest CT quantitative parameters of AECOPD patients were correlated with blood EOS level,among which LAA%,a part of WT and WA were all weakly negatively correlated with blood EOS level.
文摘Objective To evaluate the effect of the cardiopulmonary bypass (CPB) on the pulmonary function in infants with or withoutpulmonary hypertension in congential ventricular septal defect (VSD). MethodsTwenty infants with VSD were enrolled in the study fromJan. to Dec.2004. They were divided into two groups: pulmonary hypertension group and non-pulmonary hypertension group, ten infantsrespectively. Pulmonary function parameters were measured before CPB and 3, 6, 9, 12, 15, 18, 21, 24h after CPB, the following datawere recorded: duration for mechanical ventilation (Tmv) and staying in the cardiac intensive care unit (Tcicu) after cardiac surgery.Results Before CPB, the pulmonary function parameters in non-pulmonary hypertension group were more superior than in pulmonary hy-pertension group (P<0.01). By contraries, the pulmonary function parameters in every time stage after CPB statistically significant de-creased in non-pulmonary hypertension group (P<0.05), especially at 6, 9, and 15h after CPB (P<0.01). In pulmonary hyperten-sion group, the pulmonary function parameters in 3h after CPB were more improved than before CPB, though there was no statistical sig-nificance. But they had statistically significant decreased at9, 12, 15h after CPB (P<0.05). There was a similar change in pulmonaryfunction between two groups at 21, 24h after CPB. Conclusion Exposure to CPB adversely affects pulmonary function after surgicalrepair of VSD in infants. We consider that the benefits of the surgical correction in infants with pulmonary hypertension outweight the neg-ative effects of CPB on pulmonary function. We should improve cardiac function to avoid the presence of the nadir trough in pulmonaryfunction. The infants with pulomonary hypertension also have ability to wean from mechanical ventilation as soon as possible, if the hemo-dynamics is stable, and without the responsive pulmonary hypertension or pulmonary hypertension crisis after surgical repair.
基金The project supported by National Natural Science Foundation of China(81273512,81460010)by Natural Science Foundation of Jiangxi province(20142BAB215035)
文摘OBJECTIVE To explore the role of calpain in in pulmonary vascular remodeling in hypoxia induced pulmonary hypertension and the underlying mechanism.METHODS Sprague-Dawley rats were randomly divided into hypoxia group and normoxia control group.Right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(m PAP)were monitored by the method of right external jugular vein cannula.Right ventricular hypertrophy index was expressed as the ratio of right ventricular weight to left ventricular weight(left ventricle plus septum weight).Level of calpain-1,calpain-2and calpain-4 m RNA in pulmonary artery trunk were determined by real-time PCR.Expression of calpain-1,calpain-2 and calpain-4 protein was determined by Western Blot.Primary rat pulmonary arterial smooth muscle cells(PASMCs)were divided into 4 groups:normoxia control group,normoxia+MDL28170 group,hypoxia group and hypoxia+MDL28170 group.Cell proliferation was detected by MTS and flow cytometry.Level of Ki-67 and PCNA m RNA were determined by real-time PCR.RESULTS RVSP,m PAP and right ventricular remodeling index were significantly higher in the hypoxia group than those in the normoxia group.In the hypoxia group,pulmonary vascular remodeling occurred,and the expression of calpain-1,calpain-2 and calpain-4 m RNA and protein expression was increased in the pulmonary artery.MDL28170 significantly inhibited hypoxia-induced proliferation of PASMCs accompanied with decreased Ki-67and PCNA m RNA expression.CONCLUSION Calpain mediated vascular remodeling via promoting proliferation of PASMCs in hypoxia induced pulmonary hypertension.
基金The project supported by Central Public Scientific Research Institution Fundamental Project(2016CX09)by National Natural Science Foundation of China(81573645)
文摘OBJECTIVE Pulmonary artery hypertension(PAH)is a severe disease characterized by the mean pulmonary artery pressure exceeding 25 mm Hg at rest.PAH could induce right heart failure and has a very high mortality rate.At present,several kinds of drugs have been used in the treatment of PAH.However,most of these drugs aim to relax pulmonary arteries and do not inhibit the injury of vessels.In other words,the drugs available for PAH treatment do not improve the survival rate of PAH patients and cannot satisfy the needs in clinic.To discover and develop novel candidate compounds effective on the treatment of pulmonary artery injury and remodeling will be very important.Based on these background,the present study aimed to study the protective effect of two novel Rho-kinases(Rho-associated coiledcoil forming protein serine/threonine kinase,ROCK)inhibitors,DL0805 derivatives(DL0805-1and DL0805-2),on pulmonary arterial cells and further evaluate the underlying mechanisms and the possibility of DL0805 derivatives become therapeutic drugs for PAH.METHODS The primary cultured pulmonary arterial cells including human pulmonary artery endothelium cells(HPAECs)and human pulmonary artery smooth muscle cells(HPASMCs)were used in this study.HPAECs were injured under hypoxia environment(1%O2)and treated with or without DL0805 derivatives.After 48 h,the proliferation and oxidative stress were observed.CCK8 was used to detect cell viability.DCFH-DA was used as probe for reactive oxygen species(ROS)under fluorescence imaging system.HPASMCs was stimulated by growth factors including platelet-derived growth factor-BB(PDGF-BB)and Fetal Bovine Serum(FBS).The proliferation was observed in the cells treated with or without DL0805 derivatives.HPASMCs treated with or without DL0805 derivatives were further incubated with endothelin(ET-1),the proliferation and cytoskeleton remodeling of cells were detected by immunofluorescence assay.At last,Western blotting(WB)and immunofluorescence assay were employed to analysis the underlying mechanisms in the above experiments.RESULTS 10μmol·L-1DL0805-2 could inhibit the proliferation of HPAECs induced by hypoxia.Each concentration of DL0805-1 and DL0805-2attenuated the production of ROS in HPAECs.Results from WB indicated that DL0805 derivatives decreased the injury of HPAECs induced by hypoxia through the inhibition of the expression of Rho A and the activity of ROCK.On HPASMCs,DL0805 derivatives reduced the proliferation induced by PDGF-BB and FBS and inhibited cytoskeleton remodeling induced by ET-1.Immunofluorescence assay showed that DL0805 derivatives inhibited ROCK activity and down regulated the phosphorylation levels of ROCK substrates.CONCLUSION DL0805derivatives exhibited protective effect on pulmonary arterial cells including endothelium cells and smooth muscle cells.Among the above experiments,DL0805-2 showed stronger potency than DL0805-1.These two compounds might protect the cells through the inhibition of Rho A/ROCK pathway and they probably have the potential in the treatment of PAH and deserve further evaluation.
文摘Objective Cardiopulmonary exercise testing(CPET)is helpful to identify right ventriclar(RV)dysfunction in patients with rapair of Tetralogy of Fallot(rTOF),but its predictive value on early outcomes of pulmonary valve replacement(PVR)of these patients is unclear when similar preoperative ventricular size and function in cardiovascular magnetic resonance(CMR)exist.The aim of this study is to evaluate whether CPET is useful to predict the early outcomes of rTOF patients after PVR.
文摘Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregulated in the lung tissue of CHD-PAH patients,especially in the irreversible group.However,how exactly it participated in CHD-PAH development is unknown.
基金supported by National Natural Science Foundation of China(81402482,91313303)
文摘OBJECTIVE Leukotriene B4(LTB4)biosynthesis and subsequently neutrophilic inflammation may provide a potential strategy for the treatment of acute lung injury(ALI)or idiopathic pulmonary fibrosis(IPF).To provide a potential strategy for the treatment of ALI or IPF,we identified potent inhibitors of Leukotriene A4 hydrolase(LTA4H),a key enzyme in the biosynthesis of LTB4.METHODS In this study,we identified two known histone deacetylase(HDAC)inhibitors,suberanilohydroxamic acid(SAHA)and its analogue 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide(M344),as effective inhibitors of LTA4H using enzymatic assay,thermofluor assay,and X-ray crystallographic investigation.We next tested the effect of SAHA and M344 on endogenous LTB4 biosynthesis in neutrophils by ELISA and neutrophil migration by transwell migration assay.A murine experimental model of ALI was induced by lipopolysaccharide(LPS)inhalation.Histopathological analysis of lung tissue using H&E staining revealed the serious pulmonary damage caused by LPS treatment and the effect of the SAHA.We next examined m RNA and protein levels of pro-inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid using q RT-PCR and ELISA to further investigate the underlying mechanisms of anti-inflammatory activities by SAHA.We also investigated the effects of SAHA and M344 on a murine experimental model of bleomycin(BLM)-induced IPF model.RESULTS The results of enzymatic assay and X-ray crystallography showed that both SAHA and M344 bind to LTA4H,significantly decrease LTB4 levels in neutrophil,and markedly diminish early neutrophilic inflammation in mouse models of ALI and IPF under a clinical safety dose.CONCLUSION Collectively,SAHA and M344 would provide promising agents with well-known clinical safety for potential treatment in patients with ALI and IPF via pharmacologically inhibiting LAT4H and blocking LTB4 biosynthesis.
文摘Background and Objective Pulmonary hypertension (PH) is a fatal disease resulting from various causes. Studies from abroad have shown iron deficiency (ID) is closely associated with disease progression.This association is common in pulmonary arterial hypertension (PAH)that belongs to World Health Organization group 1 PH. However, ID prevalence in Chinese patients suffering from PH is unclear so far.
基金supported in part by National Sciences Foundation of China grants ( 11672001, 81571691 and 81771844)
文摘Background Tetralogy of Fallot(TOF)is the most common cyanotic heart defect,accounting for 10%of all congenital defects.Pulmonary valve stenosis(PVS)is one common right ventricular outflow tract obstruction problem in patients with TOF.Congenital bicuspid pulmonary valve(BPV)is a condition of valvular stenosis,which morphologic feature is the presence of only two pulmonary leaflets instead of the normal tri-leaflet.Congenitally BPV are uncommon and the occurrence is often associated with TOF.Methods The three-dimensional geometric reconstruction of pulmonary root(PR)were based on well-accepted mathematical analytic models with physiological parameters obtained from a typical sample of the pulmonary root used in clinical surgery.The PR geometry included valvular leaflets,sinuses,interleaflet triangles and annulus.The dynamic computational models of normal PR with tri-leaflet and PR with BPV in patients with TOF were developed to investigate the effect of geometric structure of BPV on valve stress and strain distributions and the geometric orifice area.Mechanical properties of pulmonary valve leaflet were obtained from biaxial testing of human pulmonary valve left leaflet,and characterized by an anisotropic Mooney-Rivlin model.The complete cardiac cycle was simulated to observe valve leaflet dynamic stress and strain behaviors.Results Our results indicated that stress/strain distribution patterns of normal tri-leaflet pulmonary valve(TPV)and the BPV were different on valve leaflets when the valve was fully open,but they were similar when valves were completely closed.When the valve was fully open,the BPV maximum stress value on the leaflets was 218.1 kPa,which was 128.0%higher than of the normal TPV value(95.6 kPa),and BPV maximum strain value on the leaflets was 70.7%higher than of the normal TPV.The location of the maximum stress from TPV and BPV were also different,which were found at the bottom of the valve near the leaflet attachment for TPV and the vicinity of cusp of the fusion of two leaflets for BPV,respectively.During the valve was fully open,the stress distribution in the interleaflet triangles region of the PR was more asymmetric in the BPV model compared with that in the normal TPV model,and the largest change on the PR with the geometrical variations in the two models was 39.6%in maximum stress.This stress asymmetry indicates that BPV may be one of the causes of post-stenotic pulmonary artery dilatation and aneurysm in patients with TOF.The cusp of the BPV model showed significant eccentricity during peak systolic period,and its geometric orifice area value in the completely opened position of valve was reduced 57.5%from that of the normal TPV model.Conclusions Our initial results demonstrated that valve geometrical variations with BPV may be a potential risk factor linked to occurrence of PVS in patients with TOF.Computational models could be used as an effective tool to identifying possible linkage between pulmonary valve malformation disease development and biomechanical factors,better design of artificial valves and new surgical procedures without testing those on patients.Large-scale clinical studies are needed to validate these preliminary findings.
文摘Aim Rhodiola rosea L. possesses a wide range of pharmacological properties including lung-protective, and it has been implemented in folk medicine for several 100 years. However, the accurate mechanisms of its lung- protective activity remain unclear. This study aimed at investigating the possible mechanisms of lung-protective activity of Rhodiola rosea L. in pulmonary fibrosis model. Methods Pathological observation, ROS detection and measure- ments of biochemical indexes on rat models proved lung-protective effect of Rhodiola rosea L. Identification of active compounds in Rhodiola rosea L. was executed through several methods including UPLC-TOF-MS. SEA docking, too- lecular modeling, molecular docking, and molecular dynamics （MD） simulation were applied in this study to explore possible mechanisms of the lung-protective potential of Rhodiola rosea L. Furthermore, in vitro cytological examina- tion and Western blot were used for validating the efficacy of the selected compounds. Results Experiments on rat models showed a potent lung-protective effect of Rhodiola rosea L. Then we analyzed the chemical composition of Rhodiola rosea L. and found out their key targets. Moreover, in silico analysis results testified good interaction be- tween selected compound 13 and key targets Akt-1/Caspase-1, and compound 10 also interacts well with Akt-1. Fur- ther Western blot analysis proved changed expression levels of those target proteins, indicating that selected small compounds indeed acted on those targets. Conclusion In silico analysis and experimental validation together demon- strated that selected compound 10 in Rhodiola rosea L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both Caspase-1 and Akt-1. These small compounds may ameliorate pulmonary fibrosis by acting on their targets which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Rhodiola rosea L. acting on pneumonocyte and ameliorating pulmonary fibrosis.
文摘Aim To investigate the effects of general ginsenoside on the pulmonary fibrosis in mice. Methods All the animals were divided into the sham operation group, model control group and the groups administered with gen- eral ginsenoside （40, 80, 160 mg · kg^-1） and prednisone （5 mg · kg^-1） group. The mice pulmonary fibrosis was induced by bleomycin （BLM 5 mg · kg^-1） and general ginsenoside （40, 80 and 160 mg · kg^-1） and prednisone （ 5 mg · kg^- 1 ） were given the day after surgery for 28consecutive days. The pulmonary fibrosis induced by bleomy- cin （BLM 5 mg · kg^-1） was evidenced by the pulmonary index, histopathology, and by the expression of alpha smooth muscle actin （oL-SMA）. Results Compared with that of the sham operation control, the pulmonary index were remarkably increased, Pathological examination demonstrated that BLM administration induced focal fibrotie lesions （ Alveolitis and pulmonary fibrosis） in mice lungs, and the expression of α-SMA mRNA was elevated for sev- eral time in the model control. However, compared with model control, general ginsenoside and prednisone admin- istrated could cause significantly decreases in the pulmonary index, the degree and extent of alveolitis and fibrosis had different degree of ease, reduce the elevated α-SMA mRNA expression. Conclusion General ginsenoside in- duced protection against the pulmonary fibrosis induced by bleomycin in mice.
文摘Objective To summarize the clinical characteristics and the effect of pulmonary endarterectomy(PEA)in CTEPH patients with unilateral main pulmonary artery occlusion.Methods Of 160 CTEPH patients operated between January2004 and March 2018 at our center,13(8.1%)had complete main pulmonary artery occlusion.Patients were included if the ventilation/perfusion(V/Q)scan revealed nonperfusion of an entire lung and the pathological examination showed chronic thromboembolic.
文摘Aim DL0805-2 is a novel Rho-kinases inhibitor which has been found to have potent cardiovascular effects. In the present research, we aimed to study the potential of DL0805-2 in the treatment of pulmonary arterial hypertension （PAH） and discuss the underlying mechanisms preliminarily. Methods A classical PAH animal model was used, which was established by single injection of 50 mg · kg^-1 monocrotaline （MCT）. One week later, the rats were administrated with 1, 3, 10 mg · kg^-1 DL0805-2 via intraperitoneal injection for 18 days. At the end of the experiment, the body weight and survival rate were recorded. Meanwhile, the respiration function, heart function, blood pressure and pulmonary artery pressure were detected. Serum was collected for biochemical index analysis. The weight of vital organs was used to calculate the organ index. Histopathology examination was em-ployed to observe the subtle changes in hearts, vessels and lungs. Furthermore, the mechanisms were studied main- ly by the method of western blotting. Results DL0805-2 did not show significant influence on body weight of PAH rats. But the survival rate of PAH rats treated with 3 and 10 mg · kg^-1 DL0805-2 was increased up to 90. 9% com- pared with the model group （68.2%）. DL0805-2 improved the pulmonary artery blood flow especially the maximal -1 -1 velocity （PV max） from 397.2 cm · s^-1 to 506.5, 540. 1 and 574.0 cm · s^-1 respectively. The results of echocar- diography and electrocardiogram show that DL0805-2 had little effect on left ventricle and systemic circulation but attenuated right ventricle injury and decreased the right ventricle pressure from 73.73 mmHg to 47.80, 42.64 and 46.45 mmHg respectively after DL0805-2 intervention. Disease markers of PAH including NT-proBNP in serum and ET-1 in lung tissue homogenate and serum biochemical indicators, ALT, AST and LDH, were reduced by DL0805-2. DL0805-2 also relieved edema of lungs and decreased inflammatory cytokines production. Through the examination on histopathologic slide of pulmonary main artery, right ventricle and lung, DL0805 derivatives were found to have significant protection effect on structural changes of organs induced by pulmonary hypertension. Ac- cording to the preliminary study on the mechanisms of DL0805-2 in PAH, Rho/ROCK pathway was significantly in- hibited by DL0805 derivatives. In addition, DL0805 derivatives showed effect on BMPRII/p-Smad pathway and ap- optosis related pathway. Conclusion DL0805-2 has showed potent treatment effect on the PAH rats. And the un- derlying mechanisms studies also indicated that RhoA/ROCK and BMPRII pathways were involved. This work will provide basis experimental data for the further research and development of DL0805-2.
文摘Hemodynamic responses to hypoxic challenge on rats werechecked either in anesthetic state or in awake state. The rats in awake state wereunder taken hemodynamic study at 48 hours after Pentobarbital（PB） anesthesiaand catheterization. Hemodynamic responses to hypoxic ventilation on dogs wasconducted either at 2 hours or at 4 hours after PB. During hypoxic ventilationflaxidel was used to maintain skeletal muscular relaxation, yet PB was not re-peated to diminish it’s influence on hypoxic responses. Blood gas assay was car-ried out in dogs during normoxia and hypoxic challenge. Hypoxic challengecaused significant increase of pulmonary artery pressure （Ppa） and almost nochange in systemic artery pressure （Psa） in awake rats. However in anestheticrats hypoxic challenge had little effect on Ppa, without influence on Psa. At 2and 4 hours after PB administration and catheterization hypoxic ventilationcaused similar change in blood gas （PaO<sub>2</sub> and PvO<sub>2</sub>）. However the second hy-poxic ventilation （4h） produced more significant pulmonary hemodynamic re-sponses （Ppa and TPVR greatly increased）. These results suggested thatpreferable acute hypoxic pulmonary hypertension developed either in awake ratsor in relatively shallow anesthetic state of dogs, indicating that PB anesthesiamay inhibit hypoxic pulmonary hemodynamic responses.
基金Natural Science Foundation of China(81573645,81603101)the National Science and Technology Major Project(2013ZX09103001-008)
文摘OBJECTIVE The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling,which is characteristic of pulmonary arterial hypertension(PAH).In this study we exam-ined whether salvianolic acid A(SAA)extracted from the traditional Chinese medicine′Dan Shen′attenuated vascular remodeling in a PAH rat model,and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline(MCT 60 mg·kg-1,sc).The rats were orally treated with either SAA(0.3,1,3 mg·kg-1·d-1)or a positive control bosentan(30 mg·kg-1·d-1)for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA or bosentan effectively ameliorated MCTinduced pulmonary artery remodeling,pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure(RVSP).Furthermore,the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal injury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphogenetic protein typeⅡreceptor(BMPRⅡ)and phosphorylated Smad1/5 in the lungs.CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRⅡ-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the patients at high risk of PAH.
文摘Background and Objective Ablation within the pulmonary sinus of Valsalva (PSV) becomes increasingly common in certain ventricular outflow arrhythmia. Understanding the regional anatomy is intensively concerned to avoid procedure complications. The purpose of this study is to describe the anatomic relationships of PSV to its adjacent structures using computed tomographic coronary angiograms (CTCA).
文摘Objective Hypoxemia is one of the main factors of pulmonary hypertension,and it can also be a complication of pulmonary hypertension,and it is a risk factor for many cardiovascular diseases,which increases the adverse prognosis of patients.At present,there are some controversies about the diagnosis and treatment of sleep apnea disorder in patients with pulmonary hypertension.
文摘Objective To analyze the clinical features and effects of target therapy of post splenectomy pulmonary hypertension, and improve the diagnosis and treatment of the disease.Methods Clinical data of 18 patients with post splenectomy pulmonary hypertension admitted to our hospital from October 2006 to March 2017 were systematically reviewed.
文摘Objective To investigate the risk factors associated with combined post-capillary and pre-capillary pulmonary hypertension(Cpc-PH)and the prognostic difference between isolated post-capillary pulmonary hypertension(Ipc-PH)and Cpc-PH in pulmonary hypertension due to left heart failure.Methods From October 2012 to November 2016,patients with pulmonary hypertension due to heart failure with preserved ejection fraction(PH-HFpEF)and pulmonary hypertension due to heart failure with reduced ejection fraction(PH-HFrEF)were prospectively enrolled from 11 centers all over the country.
文摘Background and Purpose Recent studies found endothelialto-mesenchymal transition(EndoMT)played an important role in the pathogenesis of pulmonary arterial hypertension.Our pilot research demonstrated the existence of Warburg effect in the lung tissue of idiopathic pulmonary arterial hypertension patients.However the relationships and the underlying mechanisms between EndoMT and Warburg effect have not been elucidated.Therefore,the purpose of this study is to determine whether metabolic reprogramming happens in EndoMT cells.We also want to investigate whether sodium dichloroacetate(DCA),a metabolic modulator,could prevent EndoMT by inhibiting Warburg effect.
