Objective To explore the pulmonary arterial pressure level in patients with predialysis chronic kidney disease ( CKD) and its relationship to cardiac structure and function. Methods 397 patients with predialysis CKD and 50 healthy subjects were enrolled. Cardiac structure was evaluated by Doppler echocardiography. Glomerular filtration rate ( GFR ) were assessed by radiant 99mTc-DTPA.Differences of PAP, BNP, LA, IVST, LVDd, LVDs, LVEF, LVMI and the correlation of PAP with cardiac structure and function were examined. Results The PAP level in the predialysis CKD patients was much higher than that in the healthy subjects [ ( 33. 13 ±9. 00) mm Hg vs. ( 29. 43 ±3. 71) mmHg, P lt;0. 01] .18. 9% of the CKD patients were complicated with pulmonary hypertension. PAP was higher in the CKD patients in stages 4-5 than those CKD patients in stages 1-3 [ ( 35. 90 ±9. 34) mmHg vs. ( 32. 08 ±8. 62)mmHg, P lt;0. 01) ] , so as to the prevalene of pulmonary hypertension ( 21. 60% vs. 13. 47% , P lt;0. 01) .Compared with the healthy, the level of lnBNP [ ( 3. 59 ±1. 63) pg/mL vs. ( 2. 88 ±1. 51) pg/mL, P lt;0. 01] , LA [ ( 40. 42 ±6. 77) mmvs. ( 36. 75 ±4. 94) mm, P lt; 0. 01) ] , LVPW [ ( 9. 55 ±1. 96) mm vs.( 8. 54 ±0. 88) mm, P lt; 0. 01) ] , IVST [ ( 9. 76 ±1. 75) mm vs. ( 8. 71 ±0. 90) mm, P lt; 0. 01) ] , LVMI[ ( 105. 61 ±36. 47) g/m2 vs. ( 87. 41 ±17. 08) g/m2 , P lt; 0. 01) ] were all much higher. There was a negative correlation between PAP and GFR( r = - 0. 461, P lt;0. 01) , and positive correlations between PAP and LA ( r=0. 491, P lt; 0. 01) , LVPW ( r =0. 298, P lt;0. 01) , IVST ( r = 0. 613, P lt;0. 01) , lnBNP ( r =0. 536, P lt;0. 01) , LVMI ( r = 0. 382, P lt;0. 01) . LVMI and lnBNP were both independent risk factors of PAP. The regression equation: y = 16. 447 + 0. 105x1 + 1. 724x2 ( F = 23. 482, P = 0. 000) , y: PAP( mm Hg) , x1 : LVMI( g/m2 ) , x2 : lnBNP( pg/mL) . Conclusions Pulmonary hypertension is a common morbidity of predialysis CKD patients, and deteriorates with degression of renal function. PAP is related to indexes of cardiac structure ( LVMI, LA, LVPW, IVST) and index of cardiac function ( lnBNP) . LnBNP and LVMI are independent risk factors of PAP.
Abstract： Objective To study the effect of different numbers of bone marrow mesenchymal stem cells（MSCs） transplanted into rats with pulmonary arterial hypertension （PAH）induced by monocrotaline（MCT）and their influence on the expression of endothelin-1（ET-1）. Methods Forty healthy male Wistar rats（weight，from 180 to 250 g） were divided into four groups by random number table（n=10）：group A：Wistar rats were intraperitoneally injected with MCT 60 mg/ kg， and then injected with 1×106 MSCs via the external jugular vein；group B：Wistar rats were intraperitoneally injected with MCT 60 mg/kg，and then injected with 5×105 MSCs via the external jugular vein；MCT group：Wistar rats were intraperitoneally injected with MCT 60 mg/kg， and then injected with equal amount of PBS via the external jugular vein； control group：Wistar rats were intraperitoneally injected with equal amount of saline and then injected with equal amount of PBS via the external jugular vein. Four weeks after MSCs transplantation，right ventricular systolic pressure（RVSP） and ventricular weight ratio of right ventricle/ （left ventricle＋ventricular septum）were measured. Histomorphology of lung tissue was observed. Genetic expression of ET-1 in lungs and serum peptide of ET-1 were also measured. Results Four weeks after MSCs transplantation，both RVSP and ventricular weight ratio decreased significantly in rats of group Acompared with those of MCT group（RVSP：35.8±4.2 mm Hg vs. 47.2±10.1 mm Hg，P＜ 0.01； ventricular weight ratio：0.357±0.032 vs. 0.452±0.056，P＜0.01）， but these two parameters didn’t decrease significantly in rats of group B（P＞ 0.05）. By histopathological staining， the percentage of medial wall thickness of the pulmonary arterioles was significantly less in rats of group A than that of MCT group（19.7%±3.0% vs. 26.8%±3.6%， P＜ 0.01）. There was no statistical difference in the percentage of medial wall thickness of the pulmonary arterioles between group B and MCT group. Reverse transcriptase-polymerase chain reaction （RTase-PCR）results showed that ET-1messenger ribonucleic acid（mRNA）expression was highest in MCT group and MSCs transplantation significantly decreasedits expression in group A， while its expression was similar between group B and MCT group. The expression ofET-1 in plasma was also significantly decreased in group A than that in MCT group. Conclusion Intravenous MSCs transplantation can significantly inhibit MCT-induced PAH，and reduce both ET-1 mRNA expression in lung and ET-1 peptide level in plasma. It’s a better choice to transplant 1×106 MSCs to inhibit PAH in rats.
Abstract： Right ventricular dysfunction or right heart failure is a complex clinical syndrome and often leads to a poor prognosis and high mortality. In order to detect right ventricular dysfunction at an early stage, provide a therapy guidance and evaluate treatment outcomes， right ventricular function evaluation has aroused more and more concern in clinical physicians. With the advantages of being non-invasive， accuracy and repetitiveness， echocardiography is used extensively in the assessment of heart function. In this review， we focus on how to use echocardiography to evaluate right ventricular function easily, efficiently， accurately and sensitively， and provide a good foundation for its further clinical application.
Objective To investigate the dynamic expression of small ubiquitin-related modifiers-1 ( SUMO-1) in lung tissue in different phases of rat model of hypoxic pulmonary hypertension( HPH) .Methods Forty Wistar rats were randomly divided into 5 groups, and exposed to normoxia or to normobaric intermittent hypoxia for 3, 7, 14 or 21 days, respectively. Mean pulmonary arterial pressure( mPAP) , right ventricle hypertrophy index ( RVHI) , and the ratio of the vessel wall area to the total area( WA% ) weremeasured. RT-PCR and in situ hybridization were used to determine the mRNA expression of SUMO-1.Immunohistochemistry and Western blot were used to determine the protein expression of SUMO-1. Results The hypoxic rats developed pulmonary vascular remodeling in pulmonary arterioles after 7 days of hypoxia,with WA% and mPAP significantly higher than those in the normal control. Pulmonary vascular remodeling aggravated with much higherWA% and mPAP afer 14 days of hypoxia, and reached the peak afer 21 days of hypoxia. SUMO-1 mRNA and protein expression markedly increased after 3 days of hypoxia, and reached peak after 14 days. After 21 days of hypoxia, SUMO-1 mRNA expression weakened but still higher than that in the normal control ( P lt; 0. 05) , and SUMO-1 protein expression remained stable. SUMO-1 mRNA and protein expression were positively correlated with mPAP, WA% and RVHI( all P lt; 0. 01) . Conclusion SUMO-1 is transcriptionally induced in lung tissue under chronic hypoxia, and thus involves in the pathogenesis of HPH.
Objective To investigate the effect of prostaglandin E1 (PGE1) on serum vascular endothelial growth factor(VEGF) in patient with pulmonary hypertension secondary to congenital heart disease and its relation to different pathologic gradings of pulmonary arterioles. Methods Fifty three patients suffering from pulmonary hypertension secondary to congenital heart disease were chosen at random to undergo active tissue test of lung, including 6 patients suffering from severe cyanosis. All of them were intravenously dripped with PGE 1 for 15 days at the speed of 10 15 ng /kg·min, 12 hours a day. Venous blood was taken for study in the morning on the day before infusion, on the 5th day, the 10th day, and the 15th day after infusion. Then the concentration of VEGF was measured by enzyme linked immunosorbent assay (ELISA). Lung biopsy was taken from each patient and pathologic grading performed according to Heath and Edwards pathologic grading. Results Fifty three patients were classified into Grade Ⅴ:9 of them belonged to Grade Ⅰ, 14 to Grade Ⅱ, 19 to Grade Ⅲ, 5 to Grade Ⅳ, the other 6 with severe cyanosis belonged to Grade Ⅴ or even severe than Grade Ⅴ. Before administration of PGE 1, serum VEGF reached the peak while the pathologic grading of pulmonary arteriole was Grade Ⅲ, VEGF level markedly decreased in Grade Ⅳ and Ⅴ. After administration of PGE 1 serum VEGF in Grade Ⅰ showed no difference with that before administration of PGE 1( P gt;0.05), VEGF decreased in GradeⅡ and Ⅲ ( P lt;0.01), slightly decreased in Grade Ⅳ ( P lt; 0.05), while patients greater or equivalent to Grade Ⅴ showed no VEGF change during the course of PGE 1 administration ( P gt;0.05). Conclusions PGE 1 can lower the VEGF level, but the extent closely relates to the degree of pathologic change in pulmonary arteriole. It might be a pre operative parameter for pathologic grading of pulmonary arteriole.
ObjectiveBased on real-word data, and compared with two common chronic respiratory diseases, interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD), this case-control study plans to investigate the risk factors and clinical characteristics of patients with combined pulmonary fibrosis and emphysema syndrome (CPFE).MethodsA retrospective case-control study was carried out to screen the clinical data of 96 patients with CPFE, 133 patients with COPD and 164 patients with ILD, analyze their demographics, clinical data, complications and related clinical indicators. Univariate analysis was used to compare the differences among the three groups, and multivariate logistic analysis was used to screen for risk factors.ResultsAll three groups were in old age with the average age of above 71 years. In terms of male ratio and smoking rate, the CPFE group (93.8%, 85.4%) was higher than the ILD group (75.0%, 64.0%), but there was no significant difference when compared with the COPD group (90.2%, 82.0%). Regarding comorbid disease, the proportion of connective tissue disease (CTD) in the CPFE group (10.4%) and the ILD group (13.4%) was higher than that in the COPD group (1.5%). The proportion of hyperlipidemia in the CPFE group (8.3%) was higher than that in the COPD group (1.5%) and the ILD group (1.2%). There were differences in the abnormal proportion of antinuclear antibody among the three groups, but no significant difference was found when compared with the CPFE group alone. The CPFE group (46.9%, 12.5%) and the ILD group (54.9%, 9.8%) were significantly higher than the COPD group (34.6%, 2.3%) in terms of carcinoembryonic antigen (CEA) abnormal proportion and cancer rate. In terms of the prevalence of pulmonary hypertension, the CPFE group (41.7%) > the COPD group (33.1%) > the ILD group (32.9%) was shown, but no statistical significance was found among the three groups.ConclusionsMale and smoking are not only risk factors for COPD but also for CPFE. At the same time, the suffering of CPFE may be affected by immune factors and hyperlipidemia. The proportion of CPFE patients complicated with cancer and CEA abnormalities is higher than COPD patients. The severity of pulmonary hypertension in CPFE patients is significantly higher than the other two diseases.
The high incidence and mortality rates existed in chronic pulmonary thromboembolism(PTE), with considerable misdiagnosis and missed diagnosis rate. The prognosis for patients with chronic thromboembolic pulmonary hypertension was poor with medical therapy. But the pulmonary thromboendarterectomy was well established.The postoperative pulmonary hypertension and reperfusion pulmonary edema are main complications and death causes. The key management after pulmonary thromboendarterectomy is important which decreases pulmonary hypertension , and prevents reperfusion pulmonary edema and re thromboembolism.
Objective To detecting the genetic etiology of a family with idiopathic pulmonary arterial hypertension and make gene diagnosis for the patient, so as to guide the targeted treatment and early intervention for the patient and her families. Methods The phenotype information of the family members was reviewed and their peripheral blood was collected for genomic DNA extraction. Exome sequencing was used to screen the mutations and proving the selected mutations by PCR-Sanger sequencing method. The pathogenicity of candidate mutation sites were searched through PubMed and related databases, and analyzed by protein function software. The judgement of pathogenicity was considered by clinical presentations and sequencing results of the patients based on Standards and guidelines for the interpretation of sequence variants revised by ACMG. Results At present, there was only one patient with pulmonary hypertension in this family, and other family members had no clinical manifestations of pulmonary hypertension. The female patient had BMPR2 gene c.1748dupA(p.Asn583Lysfs*6) heterozygous mutant. Her father and second son had BMPR2 gene c.1748dupA(p.Asn583Lysfs*6) heterozygous mutant, but none of the other members of the family had the mutation. Conclusions The heterozygous mutation of c.1748dupA (p.Asn583Lysfs*6) of BMPR2 gene is the genetic cause of the idiopathic pulmonary arterial hypertension patient, and the clinical significance of c.1748dupA(p.Asn583Lysfs*6) is pathogenic. The patient can be further diagnosed as pulmonary hypertension, primary 1 (PPH1) by gene diagnosis, and the mutant is novel and pathogenic for PPH1.
Objective To investigate the effects of simvastatin on monocrotaline-induced pulmonary hypertension in rats, and explore the potential mechanism of simvastatin by blocking heme oxygenase-1( HO-1) expression. Methods 52 male Sprague-Dawley rats were randomly divided into five groups, ie. a control group, a simvastatin control group, a pulmonary hypertension model group, a simvastatin treatment group, a ZnPP ( chemical inhibitor of HO) group. Mean pulmonary arterial pressure ( mPAP) and right ventricular systolic pressure ( RVSP) were detected by right heart catheter at 5th week. Right ventricular hypertrophy index ( RVHI) was calculated as the right ventricle to the left ventricle plus septum weight. Histopathology changes of small intrapulmonary arteries were evaluated via image analysis system.Immunohistochemical analysis was used to investigate the expression and location of HO-1. HO-1 protein level in lung tissue were determined by western blot. Results Compared with the model group, simvastatin treatment decreased mPAP and RVHI significantly [ ( 35. 63 ±5. 10) mm Hg vs. ( 65. 78 ±15. 51) mm Hg,0. 33 ±0. 05 vs. 0. 53 ±0. 06, both P lt; 0. 05 ] . Moreover, simvastatin treatment partially reversed the increase of arterial wall area and arterial wall diameter [ ( 50. 78 ±9. 03 ) % vs. ( 65. 92 ±7. 19) % ,( 43. 75 ±4. 23) % vs. ( 52. 00 ±5. 35) % , both P lt; 0. 01) . In the model group, HO-1 staining was primarily detected in alveolar macrophages. Simvastatin treatment increased HO-1 protein expression significantly, especially in the thickened smooth muscle layer and alveolar macrophages. Inhibiting HO-1 expression using ZnPP resulted in a loss of the effects of simvastatin. mPAP in the ZnPP group was ( 52. 88±17. 45) mm Hg, while arterial wall area and arterial wall diameter were ( 50. 78 ±9. 03) % and ( 52. 00 ±5. 35) % , respectively. Conclusions Simvastatin attenuates established pulmonary arterial hypertension andpulmonary artery remodeling in monocrotaline-induced pulmonary hypertension rats. The effect of simvastatin is associated with HO-1.
Objective To explore the relationship between thrombocytosis and all-cause in-hospital mortality in patients with chronic obstructive pulmonary disease (COPD) and low-risk pulmonary embolism (PE). Methods In a multicenter retrospective study on clinical characteristics, COPD patients with proven acute PE between October 2005 and February 2017 were enrolled. The patients in risk classes III-V on the basis of the PESI score were excluded. The patients with COPD and low-risk PE were divided into two groups of those with thrombocytosis and without thrombocytosis after extracting platelet count on admission. The clinical characteristics and prognosis of the two groups were compared. Multivariate logistic regression was performed to reveal an association between thrombocytosis and all-cause in-hospital mortality after confounding variables were adjusted. Results A total of 874 consecutive patients with COPD and PE at low risk were enrolled in which 191 (21.9%) with thrombocytosis. Compared with those without thrombocytosis, the thrombocytopenic group had significantly lower body mass index [(20.9±3.3) kg/m2 vs. (25.1±3.8) kg/m2, P=0.01], lower levels of forced expiratory volume in one second (FEV1) [(0.9±0.4) L vs. (1.3±0.3) L, P=0.001] and lower partial pressure of oxygen in the arterial blood (PaO2) [(7.8±1.2) kPa vs. (9.7±2.3) kPa, P=0.003]. The COPD patients with thrombocytosis had a higher proportion of cardiovascular complications as well as higher level of systolic pulmonary arterial pressure (sPAP) [(46.5±20.6) mm Hg vs. (34.1±12.6) mm Hg, P=0.001]. Multivariate logistic regression analysis after adjustment for confounders revealed that thrombocytosis was associated with all-cause mortality in hospitalized patients with COPD and low-risk PE (adjusted OR=1.53, 95%CI 1.03–2.29), and oral antiplatelet treatment was a protective factor (adjusted OR=0.71, 95%CI 0.31–0.84). Conclusions Thrombocytosis is an independent risk factor for all-cause in-hospital mortality in COPD patients with PE at low risk. Antiplatelet therapy may play a protective role in the high-risk cohort.