【Abstract】 Objective To improve the knowledge of idiopathic pulmonary arterial hypertension ( IPAH) to elevate the levels of early diagnosis and treatment. Methods The clinical data of 39 IPAH patients admitted in Beijing Anzhen Hospital from October 1997 to June 2010 were reviewed. Results Of the 39 IPAH patients, 14 cases were male and 25 cases were female, with an average age of ( 29. 7 ±16. 4)years old. Main clinical manifestations were exertional dyspnea/breathlessness ( 90. 9% ) , chest tightness( 72. 7%) , chest pain ( 30. 7% ) , cough ( 41. 0% ) , fatigue ( 48. 7% ) , syncope ( 35. 9% ) , cyanosis( 28. 2% ) , edema of lower extremity ( 43. 6%) , etc. As revealed through echocardiography, 39 cases had a mean systolic pulmonary arterial pressure ( SPAP) of ( 88. 8 ±24. 2) mmHg, with right ventricle enlargementin 37 cases and normal in 2 cases. Pulmonary angiography showed central pulmonary arterial dilatation with pruning of the peripheral blood vessels in 36 cases and normal in 3 cases. Right heart catheterization and acute vasodilator testing was performed with iloprost in 15 patients, systolic pulmonary arterial pressure was( 77. 6 ±27. 8 ) mm Hg, and positive rate was 20. 0% . 24 cases were misdiagnosed at admission, and misdiagnosis rate was 61. 5% . The average time of misdiagnosis was ( 26. 0 ±24. 5) months. 20 cases were treated with general medical therapy and 1 case was managed with lung transplantation before April 2008.Then 13 cases were given pulmonary arterial hypertension-targeted therapies, including sidenafil, iloprost or bosentan. Two patients died in hospital with a mortality rate of 5. 1% . Conclusions IPAH is uncommon and often occurs in young and middle-aged women. The symptoms are nonspecific and easily misdiagnosed.Echocardiography and pulmonary angiography are helpful in diagnosis. Right heart catheterization and acute vasodilator testing should be carried out if available. The patients should be early treated with pulmonary arterial hypertension-targeted therapies. Lung transplantation may be an option for end-stage cases.
Objective To extract and identify primary culture rat pulmonary arterial smooth cells ( PASMCs) , and investigate the effects of hypoxia on the proliferation of PASMCs. Methods Rat PASMCs were separated by the method of tissue block anchorage, and the cellular morphology was observed under light microscope. The cells were identified by projection electron microscopy, and α-smooth muscle actin ( α-SMactin)in the cells was identified by immunohistochemistry and immunofluorescence. The primary cultured PASMCs were exposed to normoxic and/ or hypoxia condition for 2, 6, 12, 24, 48 hours respectively, thenMTT assay and PCNA ( proliferating cell nuclear antigen) immunohistochemistry were used to detect the proliferation of PASMCs. Results The cells tended to be long spindle and grew in the “peak-valley”mode under light microscope. Immunology results showed that endochylema was stained in brownish yellow, and the positive rate was beyond 96% . There were dense patch, dense body and many filaments in endochylema under projection electron microscopy. MTT assay demonstrated that the A values of PASMCs expose to hypoxia were higher than that of nomoxia. Comparing with normoxia, the A values of PASMCs exposed to hypoxia increased after 12 hours ( P lt;0. 05) , significantly increased after 24 hours ( P lt;0. 01) . Compared with 2 hours’exposure to hypoxia, the A values increased after 12 hours( P lt; 0. 05) , markedly increased after 24 hours ( P lt; 0. 01 ) , which after 48 hours was similar with 24 hours. The result of PCNA immunohistochemistry was consistent with that of MTT. Conclusions The tissue explants adherent method is simple and convenient, and can easily obtain rat PASMCs with high purity and stability. Hypoxia canpromote the proliferation of PASMCs.
Congestive pulmonary arterial hypertension (PAH) is one of the most common complications of left to right shunt congenital heart disease. With the pulmonary artery pressure increasing, the shunt direction will reverse, eventually develop into Eisenmenger syndrome, and affect the patients' life. Studies in recent years have found that angiotensin -(1-7) and brain natriuretic peptide can adversely affect renin-angiotensin aldosterone system (RAAS), stromal cell derived factor can delay the pulmonary vascular remodeling, von Willebrand factor marks the pulmonary vascular endothelial function impaired, microRNA causes damage and homocysteine play a protective role in pulmonary vascular endothelial function. The RAAS activation, pulmonary vascular remodeling and endothelial dysfunction are related to the formation and development of PAH. We produced a comprehensive literature review about serological indexes in congestive PAH in this review.
Objective To explore a new surgical treatment of patients with severe congenital heart disease associated with tracheal or bronchial stenosis. Methods We retrospectively analyzed clinical data of 32 patients with severe pulmonary blood increased congenital heart disease complicated with tracheal or bronchial stenosis in our hospital between June 2010 and June 2014. There were 18 males and 13 females with an average age of 14.6±4.0 months and a weight of 8.8±3.0 kg. Results Average hospital stay was 12 days. Duration of intraoperative cardiopulmonary bypass was 65.0±21.0 min. Duration of aortic interruption was 42.0±16.0 min. Duration of postoperative ventilator was 25.0±18.0 h. ICU retention time was 4.0±1.8 d. All patients were survived. On the 9th day after surgery, the X-ray chest film revealed that the cardio-thoracic ratio was reduced compared with pre-operation but no statistical significance (P>0.05). Left ventricular end-diastolic dimension (LVEDD) was decreased (P<0.05). Pulmonary artery pressure was lower (P<0.01). The velocity of bloodstream in pulmonary artery was approximately normal. The computed tomography angiography (CTA) on the 9th day after surgery revealed that diameter of pulmonary artery in all patients reduced compared with that of pre-operation (P<0.01). Tracheal diameter of 28 patients returned to normal level and 3 patients had residual mild tracheal stenosis. All preoperative atelectasis recovered to normal level. All patients recovered completely. When the patients were followed up for 6 months to 4 years, the patients grew healthily and no abnormity occurred. Conclusion For the patients with tracheal or bronchial stenosis related to severe congenital heart disease,it is necessary to adopt surgical procedure to relieve the pressure of trachea or bronchus.The bronchial decompression surgery is a perfect and effective method for the patients with tracheal or bronchial stenosis related to severe congenital heart disease.
Objective To explore the effect of pulmonary arterial hypertension on the children with functional single ventricle in the early period after Fontan operation. Methods Forty-three children with pulmonary arterial hypertension after Fontan operation were enrolled in our department between January 2015 and December 2016. There were 24 males and 19 females at a median age of 4.3 years ranging from 2.5 to 4.8 years. The pulmonary arterial pressure was evaluated by cardiac catheterization. There were 23 children diagnosed without pulmonary hypertension (a non-PAH group) including 16 males and 7 females, while 20 patients were diagnosed with pulmonary hypertension (a PAH group) including 8 males and 12 females. Postoperative parameters related to outcomes were compared between the two groups. Results There was no death in the non-PAH group, but the mortality of children in the PAH group was 20.0% (4/20, χ2=5.34, P=0.02). The central venous pressure (t=–2.50, P=0.02), N-terminal prohormone of brain natriuretic peptide (NT-proBNP, Z=–3.50, P<0.01), peritoneal dialysis rate (χ2=5.40, P=0.02), incidence of arrhythmia (χ2=4.40, P=0.03) in the PAH group were significantly higher than those of the non-PAH group. The early postoperative utilization rate of pulmonary vascular targeting agents in the PAH group was significantly higher than that in the non-PAH group (χ2=6.30, P=0.04). Conclusion Pulmonary arterial hypertension is one of the most important factors which influence the early postoperative prognosis of children with functional single ventricle after Fontan operation.
ObjectiveTo explore the possibility that GREM1, a bone morphogenetic protein (BMP) antagonist, is a mechanical explanation for BMP signal suppression in congenital heart disease associated pulmonary arterial hypertension (CHD/PAH) patients.MethodsSystemic-to-pulmonary shunt induced PAH was surgically established in rats. At the postoperative 12th week, right heart catheterization and echocardiography evaluation were performed to evaluate hemodynamic indexes and morphology of right heart system. Right heart hypotrophy index and pulmonary vascular remodeling were evaluated. Changes of BMP signal pathway related proteins and GREM1 in lungs and plasma GREM1 concentration were detected. The effect of GREM1 on the proliferation and apoptosis of pulmonary arterial endothelial cells (PAECs) was also explored.ResultsThe hypertensive status was successfully reproduced in rats with systemic-to-pulmonary shunt model. BMP signal pathway was suppressed but GREM1 was up-regulated with no change in hypoxia inducible factor-1 in lungs exposed to systemic-to-pulmonary shunt, while this trend was reversed by systemic-to-pulmonary shunt correction (P<0.05). Immunohistochemical staining demonstrated enhanced staining of GREM1 in remodeled pulmonary arteries. In vitro experiments found that BMP signal was down-regulated but GREM1 expression and secretion were up-regulated in proliferative PAECs (P<0.05). Furthermore, BMP2 significantly inhibited PAECs proliferation and promoted PAECs apoptosis (P<0.05), which could be antagonized by GREM1. In addition, plasma level of GREM1 in rats with systemic-to-pulmonary shunt was also increased and positively correlated with pulmonary hemodynamic indexes.ConclusionSystemic-to-pulmonary shunt induces the up-regulation of GREM1 in lungs, which promotes pulmonary vascular remodeling via antagonizing BMP cascade. These results present a new mechanical explanation for BMP pathway suppression in lungs of CHD/PAH patients.
Objective To explore the clinical effect of ventricular septal defect repair and lung allograft (simply as "heart repair and lung transplant") in the treatment of ventricular septal defect complicated with severe pulmonary hypertension. Methods A 21-year-old female patient with ventricular septal defect and severe pulmonary hypertension was treated with cardiopulmonary bypass (CPB) under general anesthesia, and then right lung transplantation was performed, and then left lung transplantation was performed after changing body position. Results The operation was conducted successively. The intraoperative CPB support time was 90 minutes, and the blood loss was 2000 mL. Extracorporeal membrane oxygenation was removed on the second day after operation, the ventilator was evacuated on the third day, and the patient recovered and discharged on the 38th day. Postoperative echocardiography showed significant improvement in pulmonary artery pressure. Conclusion For patients with simple congenital heart disease complicated with severe pulmonary hypertension, "heart repair and lung transplant" can improve their quality of life.
ObjectiveTo explore the prognostic value of serum cystatin C (Cys C) in patients with congenital heart disease-associated pulmonary arterial hypertension (PAH-CHD).MethodsA retrospective cohort study was conducted on adult PAH-CHD patients who were hospitalized for the first time in the First Affiliated Hospital of Xinjiang Medical University from January 2010 to January 2020. The serum Cys C and other related data of patients were collected. The median follow-up time was 57 months. The main end event was all-cause death. According to the prognosis, the patients were divided into a survival group and a death group. Cox regression was used to analyze the risk factors for all-cause death in patients with PAH-CHD.ResultsA total of 456 patients were enrolled, including 160 males and 296 females, aged 38.99±14.72 years. The baseline data showed that there were statistical differences in resting heart rate, serum Cys C, creatinine, NT-proB-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), high-sensitivity C reactive protein (hs-CRP), New York Heart Association (NYHA) cardiac function classification and serum potassium between the survival group and the death group. Univariate Cox regression analysis showed that serum Cys C, NT-proBNP, hs-cTnT, creatinine and NYHA cardiac function classification were related risk factors for all-cause death in patients with PAH-CHD. Multivariate Cox regression analysis showed that serum Cys C (HR=3.820, 95%CI 2.053-7.108, P<0.001), NYHA grade Ⅲ (HR=2.234, 95%CI 1.316-3.521, P=0.010), NYHA grade Ⅳ (HR=4.037, 95%CI 1.899-7.810, P=0.002) and NT-proBNP (HR=1.026, 95%CI 1.013-1.039, P<0.001) were independent risk factors for all-cause death in patients with PAH-CHD and had a good predictive value.ConclusionAs a new cardiac marker, serum Cys C can predict all-cause death in patients with PAH-CHD and is an independent risk factor.
Objective To assess the effects of lung transplantation (LT) in the treatment of end-stage pulmonary arterial hypertension (PAH) and evaluated its impact on quality of life (QoL). Methods A total of 54 patients with end-stage PAH admitted to the LT center of Wuxi People’s Hospital between January 2007 and June 2019 were retrospectively analyzed. The patients were divided into surgical and non-surgical groups. Clinical data were compared between the groups. The clinical data such as symptoms, signs, biochemistry, survival rate and quality of life were compared between the two groups. The effects of lung transplantation on survival and quality of life were analyzed. The quality of life was scored by SF-36 scale. Results A total of 54 patients with end-stage pulmonary arterial hypertension who met the indications for lung transplantation were enrolled. Among them, 36 patients underwent lung transplantation and 18 patients did not undergo surgery. There were no statistical differences in gender, course of disease, disease type, symptoms between the two groups. The uric acid of the non-operation group was significantly higher than that of the lung transplantation group (P=0.014). The systolic pulmonary artery pressure (SPAP) of the non-operation group was significantly lower than that of the lung transplantation group (P=0.046). Kaplan-Meier survival curve showed that the survival rate of the operation group was higher than that of the non-operation group (P=0.0087). The quality of life assessment showed that after lung transplantation, the physical component summary and mental component summary scores of operation group were higher than those before operation (P<0.01), and also higher than non-operation group in the same period (P<0.05). Preoperative low systemic circulation blood pressure, poor cardiac function, high NT-proBNP and high uric acid may be the risk factors for early death of patients with pulmonary arterial hypertension after lung transplantation. Conclusions Lung transplantation can effectively improve survival and also QoL for patients with end-stage PH. Early detection of risk factors and preoperative assessment can help improve the perioperative survival.