Pulmonary hypertension in pregnancy has been associated with negative maternal and fetal outcomes over the past decades. With the emergence of novel treatment modalities, morbidity and mortality of women who have pulmonary hypertension in pregnancy have improved. In this review, we aim to explore the contemporary updates in the management of pre-capillary and post-capillary pulmonary hypertension in pregnancy.
Humans ; Pregnancy ; Female ; Hypertension, Pulmonary/physiopathology* ; Pregnancy Complications, Cardiovascular/diagnosis* ; Pregnancy Outcome ; Antihypertensive Agents/therapeutic use*

The mechanism of L-perilla alcohol(L-POH) in intervening hypoxic pulmonary hypertension(HPAH) was discussed based on network pharmacology, and experimental verification. The active components and potential targets of the volatile oil of Rhodiola tangutica(VORA) in the intervention of HPAH were screened by network pharmacology. The biological process of Gene Ontology(GO) and the signaling pathway enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG) were analyzed for the core targets, and a "component-common target-disease" network was constructed. Four active components were screened from VORA: L-POH, linalool, geraniol, and(-)-myrtenol. The core targets for treating HPAH were HSP90AA1, AKT1, ESR1, PIK3CA, EP300, EGFR, and JAK2. GO enrichment analysis mainly involved biological processes such as reaction to hypoxia, heme binding, and steroid binding. KEGG enrichment analysis mainly involved hypoxia-inducing factor 1(HIF-1) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and Janus kinase/activator of signal transduction and transcription(JAK/STAT) signaling pathway. The vasodilation effects of the four active components were screened by perfusion experiment of extracorporeal vascular rings, and the mechanism of the main active component L-POH was studied by channel blockers. The inhibitory effects of the four active components on the proliferation of pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia were screened by cell proliferation experiment, and the mechanism of the main active component L-POH was studied by flow cytometry, cell cycle experiment, and Western blot. The results showed that L-POH could directly act on vascular smooth muscle to relax pulmonary arterioles, induce ATP-sensitive potassium channels to open, and inhibit extracellular Ca~(2+) influx through voltage-gated calcium channels to relax blood vessels. In addition, L-POH could inhibit the abnormal proliferation of PASMCs induced by hypoxia and promote its apoptosis, and its mechanism may be related to the increase in Bax protein expression and the decrease in p-JAK2, p-STAT3, Bcl-2, and cyclinA2 protein expression. In summary, L-POH can interfere with HPAH by relaxing pulmonary arterioles and inhibiting the proliferation of smooth muscle cells.
Network Pharmacology ; Animals ; Hypertension, Pulmonary/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Hypoxia/metabolism* ; Rhodiola/chemistry* ; Signal Transduction/drug effects* ; Humans ; Monoterpenes/chemistry* ; Male ; Cell Proliferation/drug effects* ; Rats, Sprague-Dawley

Renshen Decoction is derived from the Synopsis of the Golden Chamber and is also known as Lizhong Pills or Lizhong Decoction, with the effects of warming the middle, dispelling cold, tonifying Qi, and strengthening the spleen, primarily treating spleen-stomach deficiency-cold syndrome. In modern clinical practice, Lizhong Pills and Lizhong Decoction are more frequently used, while Renshen Decoction is less common. Currently, this decoction is often applied in the treatment of gastric ulcers, infantile rotavirus diarrhea, chronic nephritis, autoimmune diabetes, allergic rhinitis, and other conditions, but reports on its use for coronary heart disease and angina pectoris are limited. Research has shown that in the original text, chest impediment(chest pain and stuffiness) includes not only coronary heart disease but also conditions such as coronary microcirculation disorders, X syndrome, coronary artery bridge, cardiomyopathy, heart valve disease, heart failure, chronic obstructive pulmonary disease, pulmonary heart disease, pulmonary arterial hypertension, hypotension, arrhythmia, and other diseases characterized by chest tightness. The name Renshen Decoction focuses on Panax ginseng without mentioning "Lizhong", indicating that its primary target is not the middle energizer but rather the deficiency of vital Qi and the collapse of the heart vessel. "Qi counterflow from the hypochondrium and rushing up to chest" encompasses acute inferior myocardial infarction combined with gastrointestinal irritation, and diseases with chest tightness as the main clinical manifestation combined with slow arrhythmias associated with vagus nerve excitement, nausea, and vomiting. Renshen Decoction is formulated for the deficiency-induced chest impediment, corresponding to the complication stage of coronary heart disease in modern clinical practice, which includes acute myocardial infarction with hypotension, cardiogenic shock, heart failure, and bradyarrhythmia. This differs from the excess-induced chest impediment addressed by Zhishi Xiebai Guizhi Decoction in the same article. The chest impediment treated by Renshen Decoction includes both the acute critical stage of cardiovascular diseases and the recovery phase of major illnesses. Pathophysiologically, the syndrome associated with Renshen Decoction may be closely related to ischemia, heart failure, hypotension, shock, and bradycardia. In terms of formula differentiation, Renshen Decoction must be distinguished from Zhishi Xiebai Guizhi Decoction and Chaihu Jia Longgu Muli Decoction. Renshen Decoction represents the ancient "Cardiac Triple Therapy".
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Coronary Disease/physiopathology* ; Heart Failure/physiopathology* ; Hypertension, Pulmonary/physiopathology* ; Hypotension/physiopathology*

Pulmonary arterial hypertension (PAH) is a clinical hemodynamic syndrome characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance leading to right heart failure and death. Vascular remodeling is the most prominent histopathological feature of PAH, which is regulated by many factors. Endoplasmic reticulum stress, calcium disorder and mitochondrial dysfunction are involved in the vascular cell proliferation and apoptosis by regulating intracellular calcium homeostasis and cellular metabolism. Epigenetic phenomenon such as DNA damage and abnormal expression of miRNA are also involved in the regulation of abnormal proliferation of vascular cells. Vascular cell phenotype switching including endothelial-mesenchymal transition and smooth muscle cell phenotype switching play an important role in abnormal proliferation of vascular cells. Vascular remodeling is produced by a variety of cells and molecular pathways, and aiming at multiple targets which is expected to find a new breakthrough in the treatment of PAH,and to improve abnormal vascular remodeling, delay or even reverse the progression of PAH.
Cell Proliferation ; Cells, Cultured ; Humans ; Hypertension, Pulmonary ; physiopathology ; MicroRNAs ; genetics ; Myocytes, Smooth Muscle ; pathology ; Pulmonary Artery ; pathology ; Vascular Remodeling ; genetics

Lymphangioleiomyomatosis (LAM) is a rare diffuse cystic lung disease. Knowledge on LAM-related pulmonary hypertension (PH) is limited. This study aimed to analyze the clinical characteristics of LAM with elevated pulmonary artery pressure (PAP) and evaluate the potential efficacy of sirolimus. The study involved 50 LAM patients who underwent echocardiography. According to the tricuspid regurgitation velocity (TRV), these patients were divided into the TRV ⩽ 2.8 m/s group and TRV > 2.8 m/s group. Both groups comprised 25 females with an average age of 38.6 ± 8.1 and 41.5 ± 8.9 years. In the TRV > 2.8 m/s group, the estimated systolic PAP (SPAP) was significantly elevated (52.08 ± 12.45 mmHg vs. 30.24 ± 5.25 mmHg, P < 0.01). Linear analysis showed that SPAP was correlated with forced expiratory volume in 1 s (FEV), diffusing capacity of the lungs for carbon monoxide, alveolar arterial oxygen gradient (PO), and 6 min walking distance (r =-0.392, -0.351, 0.450, and -0.591, respectively; P < 0.05), in which PO was a risk factor for SPAP elevation (β = 0.064, OR = 1.066, P < 0.05). Moreover, in 10 patients who received sirolimus therapy, SPAP decreased from 57.0 12.6 mmHg to 35.2 ± 11.1 mmHg. The study showed that LAM patients with PH exhibit poor pulmonary function and hypoxemia and may benefit from sirolimus treatment.
Adult ; Carbon Monoxide ; analysis ; Echocardiography ; Exercise Test ; Female ; Hemodynamics ; Humans ; Hypertension, Pulmonary ; physiopathology ; therapy ; Logistic Models ; Lymphangioleiomyomatosis ; physiopathology ; therapy ; Male ; Middle Aged ; Multivariate Analysis ; Oxygen ; blood ; therapeutic use ; Respiratory Function Tests ; Sirolimus ; therapeutic use

BACKGROUND: To study the characteristics of ventricular function in Pulmonary Hypertension (PH) Patients with different shape of Interventricular Septum (IVS) by cardiac magnetic resonance (CMR). METHODS: 36 PH patients diagnosed by right heart catheterization accepted CMR. According to the morphology of IVS, the patients were divided into two groups: the non-deformation group (10 patients) and the deformation group (26 patients). The ventricular function parameters were as follows: RV and LV end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume index (SVI), cardiac index (CI), ejection fraction (EF), and myocardial mass index (MMI). RESULTS: ANOVA analysis showed that the differences of RVEDVI, RVESVI, RVSVI, RVCI, RVEF, RVMMI, LVEDVI, LVESVI, LVSVI and LVCI were significant among the three groups. Compared with control group, RVSVI (P=0.017), RVEF (P<0.001), LVEDVI (P=0.048) and LVSVI (P=0.015) decreased in IVS non-deformation group. Compared with IVS non-deformation group, RVEDVI (P<0.001), RVESVI (P<0.001), RVCI (P=0.002) and RVMMI (P=0.017) were increased in IVS deformation group; while RVEF (P=0.001), LVEDVI (P=0.003), LVSVI (P<0.001) and LVCI (P=0.029) were decreased. Compared with the control group, RVEDVI (P<0.001), RVESVI (P<0.001), RVCI (P=0.004) and RVMMI (P=0.003) were increased in the IVS deformation group, while RVEF (P<0.001), LVEDVI (P<0.001), LVESVI (P<0.001), LVSVI (P<0.001), LVCI (P<0.001) were decreased. CONCLUSIONS Ventricular function is different in PH Patients with different IVS shape. The IVS shape can represent the changes of ventricular function in PH patients.
Adult ; Aged ; Female ; Heart ; diagnostic imaging ; physiopathology ; Humans ; Hypertension, Pulmonary ; diagnosis ; diagnostic imaging ; physiopathology ; Lung Neoplasms ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Stroke Volume ; Ventricular Function ; Ventricular Septum ; diagnostic imaging ; physiopathology

BACKGROUNDThe clinical significance of acute vasoreactivity testing (AVT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension (PAH) as controls.

METHODSWe analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test.

RESULTSThe rates of positive response to AVT were similar in the CTEPH (25/175, 14.3%) and PAH (9/80, 11.3%) groups (P > 0.05). Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide (≤1131.000 ng/L), mean pulmonary arterial pressure (mPAP, ≤44.500 mmHg), pulmonary vascular resistance (PVR, ≤846.500 dyn·s-1·m-5), cardiac output (CO, ≥3.475 L/min), and mixed venous oxygen partial pressure (PvO2, ≥35.150 mmHg). Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAP, PVR, systemic vascular resistance, CO, arterial oxygen saturation (SaO2), mixed venous oxygen saturation, partial pressure of oxygen in arterial blood (PaO2), PvO2, and intrapulmonary shunt (Qs/Qt) in the PAH and CTEPH groups (all P > 0.05). The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT-responders although the difference was not statistically significant (χ2 =3.613, P = 0.057). The survival time of patients with CTEPH who received calcium channel blockers (CCBs) was longer than that in the group with only basic treatment and not shorter than that of patients who receiving targeted drugs or underwent pulmonary endarterectomy (PEA) although there was no significant difference between the four different treatment regimens (χ2 =3.069, P = 0.381).

CONCLUSIONSThe rates of positive response to AVT were similar in the CTEPH and PAH groups, and iloprost inhalation induced similar changes in hemodynamics and oxygenation dynamics indices. A positive response to AVT in the CTEPH group was significantly correlated with milder disease and better survival. Patients with CTEPH who cannot undergo PEA or receive targeted therapy but have a positive response to AVT might benefit from CCB treatment.

Administration, Inhalation ; Adult ; Aged ; Arterial Pressure ; drug effects ; Atrial Natriuretic Factor ; metabolism ; Calcium Channel Blockers ; administration & dosage ; therapeutic use ; Endarterectomy ; Familial Primary Pulmonary Hypertension ; drug therapy ; physiopathology ; Female ; Hemodynamics ; drug effects ; Humans ; Hypertension, Pulmonary ; drug therapy ; physiopathology ; Iloprost ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Protein Precursors ; metabolism ; Retrospective Studies ; Software ; Vasodilator Agents ; administration & dosage ; therapeutic use

OBJECTIVETo preliminarily investigate the relationship between serum apelin level and pulmonary artery pressure in children with congenital heart disease.

METHODSOne hundred and twenty-six children with congenital heart disease undergoing surgical treatment were enrolled as subjects. The serum level of apelin was determined before surgery and at 7 days after surgery. The ratio of pulmonary artery systolic pressure to aortic systolic pressure (Pp/Ps) was calculated before extracorporeal circulation. According to the Pp/Ps value, patients were classified into non-pulmonary arterial hypertension (PAH) group, mild PAH group, moderate PAH group, and severe PAH group. Pulmonary artery mean pressure was estimated by echocardiography at 7 days after surgery.

RESULTSThe non-PAH group had the highest serum level of apelin before and after surgery, followed by the mild PAH group, moderate PAH group, and severe PAH group (P<0.05). All groups had significantly increased serum levels of apelin at 7 days after surgery (P<0.05). The serum level of apelin was negatively correlated with pulmonary artery pressure before surgery (r=-0.51, P<0.05) and at 7 days after surgery (r=-0.54, P<0.05).

CONCLUSIONSThe decrease in serum apelin level is associated with the development of pulmonary hypertension in children with congenital heart disease. The significance of serum apelin in predicting the development and degree of pulmonary hypertension in children with congenital heart disease deserves further studies.

Apelin ; Blood Pressure ; Child, Preschool ; Female ; Heart Defects, Congenital ; blood ; physiopathology ; Humans ; Hypertension, Pulmonary ; blood ; Infant ; Intercellular Signaling Peptides and Proteins ; blood ; Male ; Pulmonary Artery ; physiopathology

OBJECTIVETo study the serum level of carbohydrate antigen 125 (CA125) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and its relation with pulmonary hypertension.

METHODSForty-six patients with AECOPD complicated by pulmonary hypertension, 46 with AECOPD and 38 healthy control subjects were examined for their clinical data, pulmonary function, echocardiographic findings, and serum levels of lung tumor markers and brain natriuretic peptide (BNP).

RESULTSCompared with the healthy control group, COPD patients with or without pulmonary hypertension showed significantly decreased pulmonary function (P<0.05), especially in those with AECOPD and concurrent pulmonary hypertension (P<0.05). Serum CA125 level was obviously higher in AECOPD group than in the healthy control group, and further increased in AECOPD patients with pulmonary hypertension (P<0.05). The levels of lung tumor markers (CEA, NSE, CYFRA and PROGRP) were similar among the 3 groups (P>0.05). The serum level of BNP in patients with AECOPD and concurrent pulmonary hypertension was significantly higher than that in patients with AECOPD (P<0.05). Pearson linear correlation analysis showed that serum CA125 was positively correlated with pulmonary artery systolic pressure and BNP in AECOPD patients with pulmonary hypertension (P<0.01).

CONCLUSIONSerum CA125 may serve as a serological index to identify AECOPD patients with pulmonary hypertension.

Acute Disease ; Biomarkers, Tumor ; CA-125 Antigen ; blood ; Case-Control Studies ; Disease Progression ; Humans ; Hypertension, Pulmonary ; physiopathology ; Lung ; Natriuretic Peptide, Brain ; blood ; Pulmonary Disease, Chronic Obstructive ; blood ; physiopathology

BACKGROUNDFibrosing mediastinitis (FM) is a rare disease. FM is thought to be related to prior granulomatous mediastinal infection, such as histoplasmosis or tuberculosis. The majority of cases have been reported in endemic regions for histoplasmosis. The characteristics of cases of FM in China, where the prevalence of tuberculosis is high, have not been reported. We analyzed the clinical, imaging, and bronchoscopic features of Chinese patients with FM to promote awareness of this disease.

METHODSBetween January 2005 and June 2015, twenty patients were diagnosed with FM in our hospital. Medical records and follow-up data were collected. Imaging and biopsy findings were reviewed by radiologists and pathologists.

RESULTSA total of 20 patients were analyzed (8 males and 12 females). The age ranged from 43 to 88 years with a mean age of 69.5 years. Previous or latent tuberculosis was found in 12 cases. Clinical symptoms included dyspnea (18/20), cough (17/20), expectoration (7/20), and recurrent pneumonia (3/20). Chest computed tomography scans showed a diffuse, homogeneous, soft tissue process throughout the mediastinum and hila with compression of bronchial and pulmonary vessels. Calcification was common (15/20). Pulmonary hypertension was present in 9 of 20 cases. Diffuse black pigmentation in the bronchial mucosa was frequently seen on bronchoscopy (12/13). The patients' response to antituberculosis treatment was inconsistent.

CONCLUSIONSFM in Chinese patients is most likely associated with tuberculosis. Some characteristics of FM are different from cases caused by histoplasmosis.

Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; China ; Female ; Histoplasmosis ; complications ; diagnosis ; Humans ; Hypertension, Pulmonary ; diagnosis ; physiopathology ; Male ; Mediastinitis ; diagnosis ; etiology ; physiopathology ; Middle Aged ; Sclerosis ; diagnosis ; etiology ; physiopathology ; Tuberculosis ; diagnosis ; physiopathology