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 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.
Pulmonary arterial hypertension(PAH) is a kind of pulmonary hypertension disease. Recently, the researches of its pathogenesis have reached more and more deeply. The treatment of pulmonary arterial hypertension is individual and systematic, not only relying on medicine treatment. The treatment of PAH is as follows: common treatment, non-specific medicine treatment, targeted medicine treatment, NO breath-in treatment, gene treatment, intervention and surgery treatment.The article reviews the main treatment of pulmanory arteral hypertesion to provide new thought and evidence in clinic.
ObjectiveTo investigate the expression of CD4+CD25highCD127lowTreg (Treg) and related cytokines in peripheral blood of COPD patients with pulmonary hypertension and explore its clinical significance. MethodsPeripheral blood lymphocytes and serum were collected from 65 COPD patients with chronic pulmonary hypertension (the CPH group) and 20 COPD patients with normal pulmonary artery pressure (the control group). Flow cytometry was used to detect the Treg/CD4+ T cells and calculate its ratio, enzyme-linked immunosorbent assay was used to detect the serum contents of interleukin (IL)-6,IL-10 and tumor necrosis factor α (TNF-α). ResultsTreg can be detected in the peripheral blood of patients of COPD with or without PH, however, the Treg ratio in the CPH group was significantly lower than that in the control group [(7.41±1.12)% vs. (9.04±2.11)%, P<0.05]. Compared with the control group, the IL-10 level was significantly lower [(4.47±0.88)pg/mL vs. (5.18±0.26)pg/mL], while IL-6and TNF-α contents were significantly higher in the CPH group [(7.49±0.95)pg/mL vs. (6.76±0.35)pg/mL, (28.61±9.16)pg/mL vs. (19.64±4.85)pg/mL, P<0.05]. There was a positive correlation between Treg ratio and serum IL-10 level (r=0.41, P<0.05), and negative correlation between Treg ratio and TNF-α or IL-6 contents (r=0.45 or 0.37,P<0.05). The Treg ratio of the patients with severe pulmonary hypertension was lower than that in the patients with mild pulmonary hypertension [(7.42±1.03)% vs. (10.47±2.55)%,P<0.05). ConclusionsContents of Treg and IL-10 decrease while IL-6 and TNF-α increase in peripheral blood of COPD patients with pulmonary hypertension. It suggests that Treg cells and related cytokines may involve in the pathogenesis and progression of CPH. Treg may becomea potential biological prognosis indicator and treatment target of CPH in the future.
Objective To analyze the relation between preoperative pulmonary artery pressure(PAP) and postoperative complications in heart transplant patients, and summarize the experience of perioperative management of pulmonary hypertension (PH), to facilitate the early period heart function recovery of postoperative heart transplant patients. Methods A total of 125 orthotopic heart transplant patients were divided into two groups according to preoperative pulmonary arterial systolic pressure(PASP) and pulmonary vascular resistance(PVR), pulmonary [CM(1583mm]hypertension group (n=56): preoperativePASPgt;50 mm Hg or PVRgt;5 Wood·U; control group (n=69): preoperative PASP≤50 mmHg and PVR≤5 Wood·U. Hemodynamics index including preoperative cardiac index (CI)，preoperative and postoperative PVR and PAP were collected by SwanGanz catheter and compared. The extent of postoperative tricuspid regurgitation was evaluated by echocardiography. Postoperative pulmonary hypertension was treated by diuresis，nitrogen oxide inhaling，nitroglycerin and prostacyclin infusion, continuous renal replacement therapy(CRRT)and extracorporeal membrane oxygenation(ECMO). Results All patients survived except one patient in pulmonary hypertension group died of multiorgan failure and severe infection postoperatively in hospital. Acute right ventricular failure occurred postoperatively in 23 patients, 10 patients used ECMO support, 10 patients with acute renal insufficiency were treated with CRRT. 124 patients were followed up for 2.59 months，7 patients died of multiple organ failure, infection and acute rejection in follow-up period, the survivals in both groups have normal PAP, no significant tricuspid regurgitation. No significant difference in cold ischemia time of donor heart, cardiopulmonary bypass(CPB) and circulation support time between both groups; but the patients of pulmonary hypertension group had longer tracheal intubation time in comparison with the patients of control group (65±119 h vs. 32±38 h, t=2.17，P=0.028). Preoperative PASP，mean pulmonary artery pressure(MPAP) and PVR in pulmonary hypertension group were significantly higher than those in control group, CI was lower in pulmonary hypertension group ［PASP 64.30±11.50 mm Hg vs. 35.60±10.20 mm Hg; MPAP 43.20±8.50 mm Hg vs. 24.20±7.20 mm Hg; PVR 4.72±2.26 Wood·U vs. 2.27±1.24 Wood·U; CI 1.93±0.62 L/（min·m2） vs. 2.33±0.56 L/（min·m2）; Plt;0.05］. Postoperative early PASP, MPAP and PVR in pulmonary hypertension group were significantly higher than those in control group (PASP 35.40±5.60 mm Hg vs. 31.10±5.70 mm Hg, MPAP 23.10±3.60 mm Hg vs. 21.00±4.00 mm Hg, PVR 2.46±0.78 Wood·U vs. 1.79±0.62 Wood·U; Plt;0.05). Conclusion Postoperative right heart insuficiency is related to preoperative pulmonary hypertension in heart transplant patients. Donor heart can quickly rehabilitate postoperatively by effectively controlling perioperative pulmonary hypertension with good follow-up results.
Pulmonary hypertension (PH), characterized by diverse etiologies and intricate pathological mechanisms, is a complex cardiopulmonary vascular disorder featuring high morbidity and mortality. Percutaneous pulmonary artery denervation (PADN) represents an emerging interventional treatment method, which shows good prospects in the clinical practice of PH. The PADN has attained preliminary achievements in terms of safety and efficacy. Nevertheless, its long-term prognosis, the characteristics of the appropriate patient populations, and the optimization strategies combined with targeted pharmacotherapy remain to be further explored. This article reviews the current clinical applications of PADN as well as the challenges it confronts.
ObjectiveTo observe the relationship of serum tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and C-reactive protein (CRP) with obstructive sleep apnea hypopnea syndrome (OSAHS) associated pulmonary hypertension (OSAHS-PH). MethodsFrom September 2013 to October 2014, 38 OSAHS patients, 32 OSAHS-PH patients and 35 healthy subjects were enrolled from the General Hospital of Ningxia Medical University. OSAHS was diagnosed by polysomnography. The pulmonary artery systolic pressure (PASP) was measured by echocardiograph, and the diagnose criteria for pulmonary hypertension was PASP≥40 mm Hg. Serum TNF-α, IL-6, CRP and endothelin 1 (ET-1) were detected by enzyme-linked immunosorbent assay. The correlation between TNF-α, IL-6, CRP, ET-1 and PASP was analyzed. ResultsThe serum levels of TNF-α, IL-6, CRP and ET-1 were remarkably different among three groups (F=55.34, 25.05, 23.85, 34.06 respectively; all P < 0.05). The levels of TNF-α, IL-6, CRP and ET-1 in the OSAHS group were higher than those in the healthy group, and lower than those in the OSAHS-PH group (all P < 0.05). The PASP was positively correlated with the levels of the four factors (r=0.755, 0.762, 0.747, 0.759 respectively; all P < 0.01). ConclusionThe levels of serum TNF-α, IL-6 and CRP are correlated with pulmonary hypertension and they may be involved in the process of OSAHS-PH.
ObjectiveTo investigate the effect and incidence of residual leakage after surgical repair of large ventricular septal defects with moderate to severe pulmonary hypertension using cross-linkage mattress suture, a suture method invented by us, as compared with interrupted mattress suture. MethodsWe retrospectively analyzed the clinical data of 41 patients of large ventricular septal defect with moderate to severe pulmonary hypertension underwent surgery using cross-linkage mattress suture in Beijing Anzhen Hospital from February 2011 through April 2013. The 41 patients were as a cross-linkage group (average age 18.7±12.3 years, the ratio of male to female 31:10). Another 41 patients, who were repaired using interrupted mattress suture, were retrospectively chosen by matching age, size and location of the defects, pulmonary artery pressure and vascular resistance with members from the cross-linkage group, and were assigned as a control group (average age 17.4±11.8 years, the ratio of male to female 31:10). ResultsThere was no operative mortality and no new perioperative atrioventricular conduction block. Postoperative echocardiography revealed the incidence of residual leakage was 31.7% (13/41) in the control group, 0% (0/41) in the cross-linkage group with a statistical difference (χ2=13.164, P=0.000). With a follow-up of 18.2±6.1 months, no late death and no new atrioventricular conduction block occurred. There was no statistical difference in New York Heart Association functional class or pulmonary artery pressure measured through echocardiography between the two groups. While there was a statistical difference in incidence of residual leakage between the the cross-linkage group and the control group (0% (0/41) versus 26.8% (11/41), χ2=10.499, P=0.001). ConclusionThere is a high incidence of residual leakage after the surgical repair of large ventricular septal defect complicated with moderate to severe pulmonary hypertension using interrupted mattress suture, while the use of cross-linkage mattress suture can effectively reduce the incidence of residual leakage.
Objective To systematically review whether the prevalence of left ventricular diastolic dysfunction was higher in systemic sclerosis (SSc) patients. Methods The Cochrane Library, PubMed, EMbase, CBM, CNKI and WanFang Data databases were electronically searched to collect the studies about comparing echocardiographic parameters in SSc patients and controls from January 1990 to June 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software. Results A total of 22 studies involving 1 146 patients were included. The results of meta-analysis showed that: compared to controls, patients with SSc had prolonged left isovolumetric relaxation time (MD=10.40, 95%CI 4.04 to 16.77, P=0.001), higher trans-mitral A-wave velocity (MD=0.11, 95%CI 0.07 to 0.15, P<0.000 01), prolonged mitral deceleration time (MD=8.04, 95%CI 2.66 to 13.42,P=0.003), larger mean left atrial dimension (MD=1.43, 95%CI 0.11 to 2.76, P=0.03), higher estimated pulmonary artery pressure (MD=11.35, 95%CI 6.08 to 16.6, P<0.001), higher E/E’ ratio (MD=2.08, 95%CI 0.19 to 3.96,P=0.03) and lower trans-mitral E-wave velocity (MD=–0.03, 95%CI –0.05 to –0.01, P=0.000 3), mitral E/A ratio (MD=–0.24, 95%CI –0.32 to –0.15, P<0.000 01) and trans-mitral E’-wave velocity (MD=–1.52, 95%CI –2.44 to –0.60,P=0.001). There were no differences in left ventricular ejection fraction, isovolumetric end-systolic dimension, septal end-diastolic thickness and posterior wall end-diastolic thickness, trans-mitral A’-wave velocity, E’/A’ ratio. Conclusion SSc patients are more likely to have echocardiographic parameters of LVDD. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.