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.
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.
ObjectiveTo explore the relevance of the ratio of pulmonary arterial diameter to aortic diameter exceeding one (PA:A>1) with brain natriuretic peptide (BNP) and inflammatory factor levels in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). MethodsFrom August 2013 to December 2013,95 inpatients with AECOPD in West China Hospital were divided into two groups according to the ratio of pulmonary arterial diameter to aortic diameter. The clinical data of the patients were collected. Meanwhile,arterial blood gas,plasma levels of BNP,C-reactive protein (CRP),and interleukin-6 (IL-6) within 24 hours were measured. ResultsThe plasma BNP level was 2005(483-4582)ng/L in the group with PA:A>1,and 404(137-1224)ng/L in the group with PA:A<1. There was significant difference in plasma BNP level between two groups (P<0.01). There was no significant difference in CRP or IL-6 level between two groups (P>0.05). ConclusionThe ratio of pulmonary arterial diameter to aortic diameter is correlated with BNP level in patients with AECOPD,but is not correlated with CRP or IL-6.
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 investigate independent prognostic factors influencing the prognosis of connective tissue disease-associated interstitial lung disease with pulmonary hypertension (CTD-ILD-PH), and construct a nomogram model using machine learning to predict 1-, 3- and 5-year mortality risks, providing evidence for clinical diagnosis and treatment. Methods Patients diagnosed with CTD-ILD-PH and treated at the First Affiliated Hospital of Zhengzhou University from February 2011 to June 2021 were screened. The least absolute shrinkage and selection operator (Lasso), univariate Cox regression, and multivariate Cox regression analyses were combined to identify independent prognostic factors for CTD-ILD-PH patients. A novel nomogram prognostic model was constructed and internally validated using 1000 bootstrap resamples. The receiver operating characteristic (ROC) curve and Harrell's C-index assessed the predictive performance of the model. Calibration curves evaluated the model fit. Decision curve analysis (DCA) assessed the clinical utility of the model, and external validation was conducted using a separate test set. Results The study included 313 patients, with 108 deaths observed during the follow-up. Using the Lasso-Cox method, albumin, alanine aminotransferase (ALT), red cell volume distribution width (RDW), age, smoking history, rural residence, and pulmonary artery systolic pressure were identified as independent prognostic factors. The Harrell's C-index in the training set was 0.802, and the area under ROC curve was 0.880 (95%CI 0.833 - 0.928). Internal validation showed an average Harrell's C-index of 0.791. Calibration curves indicated high consistency between predicted and observed results. DCA confirmed the model's good clinical utility. External validation results demonstrated the model's favorable predictive performance and clinical utility. Conclusions Our research suggest that lower albumin, elevated ALT, elevated RDW, advanced age, smoking history, rural areas and higher pulmonary artery systolic blood pressure are independent prognostic risk factors for patients with CTD-ILD-PH. In this study, a prognostic model was developed for the first time to predict 1-, 3- and 5-year mortality in CTD-ILD-PH patients, which provides some reference value for future mortality risk assessment in CTD-ILD-PH.
Pulmonary hypertension is a disease characterized by pulmonary artery pressure increased, with or without small artery pathological change, which ultimately leads to right heart failure or even death. Pulmonary hypertension seriously threatens to human health, however, the pathogenesis of pulmonary hypertension is unclear. Previous studies have found that bone morphogenetic protein (BMP) signaling system played an important role in the progress of pulmonary hypertension. In the current review, we describe the mechanism of BMP4 in the development of pulmonary hypertension.
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.
Objective To investigative the effects of combination treatment with simvastatin and aspirin in a rat model of monocrotaline-induced pulmonary hypertension. Methods Sixty male Sprague-Dawley rats were randomly divided into a control group, a simvastatin group, an aspirin group, and a combination treatment group. The control group received monocrotaline injection subcutaneously to induce pulmonary hypertension. Simvastatin ( 2 mg/kg) , aspirin ( 1 mg/kg) , or simvastatin ( 2 mg/kg) + aspirin ( 1 mg/kg) was administered once daily to the rats of treatment groups respectively for 28 days after monocrotaline injection. Mean pulmonary arterial pressure ( mPAP) was detected by right heart catheter.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 analysissystem. Interleukin-6 ( IL-6) level in lung tissue was determined by ELISA.Results Compared with the control group, simvastatin or aspirin decreased mPAP [ ( 34. 1 ±8. 4) mm Hg, ( 38. 3 ±7. 1) mmHg vs.( 48. 4 ±7. 8) mmHg] and increased arterial wall diameter significantly ( P lt; 0. 05) . The combination treatment group showed more significant improvement in mPAP, RVHI and pulmonary arterial remodeling compared with each monotherapy ( P lt;0. 05) . Moreover, the combination therapy had additive effects on the increases in lung IL-6 levels and the perivascular inflammation score. Conclusions Combination therapy with simvastatin and aspirin is superior in preventing the development of pulmonary hypertension. The additive effect of combination therapy is suggested to be ascribed to anti-inflammation effects.
ObjectiveTo investigate the clinical features and prognosis of fibrinous mediastinum and evaluate the value of different examinations in diagnosis and evaluation. MethodsTwenty-eight patients with mediastinal fibrosis diagnosed between January 2015 and September 2020 in China-Japan Friendship Hospital were studied retrospectively. The Clinical manifestations, radiological characteristics, endoscopic features, echocardiography, V/Q SPECT, cardiac catheterization, treatment and prognosis were analyzed.ResultsThe main clinical symptoms were cough (77.6%), expectoration (57.1%), wheezing or suffocating (42.9%), dyspnea (39.3%). There were 67.9% of the cases who were considered previous or present tuberculosis. Imaging findings showed that the fat density in the mediastinum disappeared, the irregular soft tissue of the mediastinum surrounded the airway and pulmonary vessels, and many lymph nodes enlarged and calcified, and multiple bronchus and pulmonary vessels were compressed and narrowed. Pulmonary function was mainly manifested as obstructive ventilate dysfunction and decreased diffusion volume. Under bronchoscopy, the bronchial mucosa showed pigmentation, bronchial distortion or multiple stenosis, even occlusion, and bronchial mucosa edema or congestion. Echocardiography and catheterization of the right heart showed that pulmonary hypertension and diastolic cardiac dysfunction were common complications of fibrillary mediastinum. Pulmonary ventilation perfusion imaging showed impaired blood perfusion in 87.5% of patients and impaired ventilation perfusion in 37.5% of patients. The symptoms of some patients alleviated after anti-infective and symptomatic treatment, but the mediastinal fibrosis was irreversible, and the efficacy of anti-tuberculosis and glucocorticoid therapy was limited. ConclusionsFor patients with clinical consideration of fibrous mediastinum, chest enhanced CT should be performed for clear diagnosis. Relevant examinations, such as pulmonary function, endoscopic, echocardiography, should be conducted to evaluate whether the disease involves airway, pulmonary vessels, pericardium, superior vena cava and esophagus, as well as the degree of functional involvement. Attention should be paid to the evaluation of patients with pulmonary hypertension and diastolic cardiac insufficiency.
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.