Descriptive spectrum of thiamine deficiency in pregnancy: A potentially preventable condition.

OBJECTIVE: Pregnancy, a nutritionally demanding situation in terms of macro- and micronutrient supply owing to heightened maternal, placental, and fetal needs, significantly affects thiamine reserves. Thiamine deficiency during pregnancy and the postpartum period, presenting with varied manifestations and outcomes, is a relatively common condition in our population. The study aimed to understand the various manifestations and outcomes of acute thiamine deficiency in pregnant and postpartum women, emphasizing the significance of early recognition and thiamine therapy to prevent serious complications during pregnancy and after childbirth. METHODS: This prospective study conducted in a tertiary care center in North India enrolled consecutive pregnant and postpartum women presenting with clinical features consistent with thiamine deficiency disorders, such as thiamine deficiency-related neuropathy, high-output heart failure, heart failure with reduced ejection fraction, Wernicke's encephalopathy, gastric beriberi, and thiamine-responsive acute pulmonary hypertension. In addition to capturing medical history including drug intake, dietary consumption, and comorbidities, women underwent brief relevant clinical examinations and laboratory assessments, including whole-blood thiamine levels. Response to intravenous thiamine supplementation was also monitored. RESULTS: Data of 31 women (12 pregnant, 19 postpartum) with a diagnosis of acute thiamine deficiency and a mean age of 28.88 ± 2.69 years were analyzed. The mean thiamine level was 1.28 ± 0.44 µg/dL with mean blood lactate of 3.46 ± 3.33. The most common presentation was gastric beriberi (n = 10), followed by paraparesis (n = 6), high-output heart failure (n = 6), acute pulmonary hypertension, heart failure with reduced ejection fraction (n = 3 each), and an acute confusional state (n = 2). All patients responded to thiamine challenge. CONCLUSION: In the context of borderline thiamine status, particularly in our population with endemic thiamine deficiency and heightened demand for thiamine during pregnancy and the peripartum period, the deficiency can have varied and serious manifestations of dry and wet beriberi. Early recognition of the clinical features and thiamine therapy can be life-saving. There is a need for validated clinical criteria owing to the non-availability of thiamine testing in resource-limited settings.

Electrophysiological study and radiofrequency ablation of hemodynamically-instable ventricular arrhythmias in a patient with pulmonary hypertension: A case report.

INTRODUCTION: Hemodynamically-instable ventricular arrhythmias (VAs) are rare in patients with pulmonary hypertension (PH). To the best of our knowledge, only 1 case has been reported so far. Moreover, the pathogenesis of this kind of arrhythmia remains obscured and its treatment is challenging. Here we report another case and presented the substrate for VAs initiation and therapeutic effect of radiofrequency ablation. PATIENT CONCERNS: This is a 57-year-old man who presented paroxysmal palpitation associated with presyncope at rest. Surface electrocardiogram (ECG) revealed frequent ventricular premature contractions and non-sustained ventricular tachycardia when symptoms occurred. He also had a history of severe PH which was secondary to atrial septal defect and partial anomalous pulmonary venous drainage and suffered from obvious dyspnea when climbing stairs World Health Organization Class III (WHO Class III). DIAGNOSIS: Hemodynamically-instable VAs associated with severe PH. INTERVENTION: Echocardiography revealed enlargement of right ventricle (right ventricle [RV]: 43 mm). Electrophysiological examination showed the origin of VAs is next to a small low-voltage zone of RV. Radiofrequency delivery at the origin successfully terminated VAs without occurrence of complication. OUTCOME: The patient was free from arrhythmias and got an improvement of exercise tolerance, just with mild dyspnea when climbing stairs World Health Organization Class II (WHO class II), during six-month follow up. LESSONS: This case suggests the low-voltage zone of remodeled RV, which may be secondary to increased pulmonary artery pressure, serves as the substrate for VAs initiation in patient with PH. Radiofrequency ablation can successfully terminate VAs and the termination of VAs can significantly improve the patient's impaired exercise tolerance.

Integrated Review of Psychosocial and Behavioral Health Assessments and Interventions in Pulmonary Hypertension.

BACKGROUND: The medical management of patients with pulmonary hypertension (PH) has advanced, with few evidence-based recommendations about psychosocial and behavioral health interventions. There is also a lack of comprehensive understanding of PH psychosocial and behavioral health needs. Some psychosocial and behavioral health interventions have been tested; however, there is a gap in the systematic evaluation of nonpharmacological complementary approaches to augment PH management when addressing psychosocial and behavioral health needs. OBJECTIVES: The objectives are to explore psychosocial and behavioral health needs and describe psychosocial and behavioral health interventions for patients with PH. METHODS: We conducted an integrative systematic review of publications between January 1, 2010, and January 31, 2020, obtained from electronic databases: EMBASE, PubMed, Cumulative Index of Nursing and Allied Health Literature, Cochrane, PsycINFO, and Web of Science. The literature searches focused on empirical literature reporting psychosocial needs and psychosocial and behavioral health interventions for adult PH patients. We included peer-reviewed studies published in English. Search terms used in the study were: "hypertension," "pulmonary hypertension," "psychosocial," "depression," "anxiety," "quality of life," "behavioral health," "self-management," "psychosocial intervention," and "psychological distress." Excluded were opinion and discussion publications, reviews, non-PH populations, and pediatric articles. We used the constant comparison method to guide the synthesis of reports applying the Joanna Briggs quality assessment guidelines. RESULTS: A total of 44 articles meeting the criteria were included for final consideration. We conducted an integrative systematic review of 27 quantitative studies, narrative synthesis of 10 qualitative studies, and 7 psychosocial and behavioral health intervention studies. PH patients reported psychosocial needs, such as financial, social connections, sexual health, and palliative care needs, as well as levels of psychological distress symptoms. The results from both quantitative and qualitative studies revealed similar overarching psychosocial and behavioral health conceptual categories. Patients described their ongoing needs in PH management by relying on their psychosocial and behavioral health capabilities to adjust to changes at each stage of disease progression. Patients had high levels of psychosocial and behavioral health needs requiring interventions beyond medical treatment. DISCUSSION: Pilot studies testing psychosocial and behavioral health interventions reported improvement in levels of anxiety and depression and health-related quality of life. Larger scale studies are needed to advance this knowledge. Psychosocial and behavioral health interventions with cognitive-guided foci have the potential of meeting these unmet needs.

High dose folic acid is a potential treatment for pulmonary hypertension, including when associated with COVID-19 pneumonia.

BACKGROUND: Pulmonary hypertension is a significant complication for some patients with COVID-19 pneumonia, especially those requiring intensive care. Tachyphylaxis to the current therapy, inhaled nitric oxide (iNO), is also common. In vitro, folic acid directly increases nitric oxide (NO) production and extends its duration of action; effects which could be of benefit in reversing pulmonary hypertension and severe hypoxaemia. Our work has shown that, in the systemic circulation, folic acid in high dose rapidly improves nitric oxide mediated vasodilation, by activating endothelial nitric oxide synthase (eNOS). HYPOTHESIS: A similar effect of high dose folic acid on pulmonary endothelial function would be expected from the same mechanism and would lead to improvement in pulmonary perfusion. We therefore hypothesise that folic acid, 5 mg or greater, is a useful therapeutic option for pulmonary hypertension and/or refractory severe hypoxaemia, in patients with severe COVID-19 associated pneumonia in whom NO therapy is considered, with a very low risk of adverse effects.

Protective Effect of Statins on Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease Patients: A Nationwide Retrospective, Matched Cohort Study.

In Taiwan, patients with pulmonary hypertension (PH) related to chronic obstructive pulmonary disease (COPD) are most common PH population (group 3). However, efficacy of medical treatments and optimal prevention methods in this group remain uncertain. Statins such as indirect RhoA/Rho-kinase inhibitors influence one of key signalling pathways that promote PH onset. In this study, we explored protective effects of statins against PH in COPD patients using database from Taiwan National Health Insurance programme from 2002 to 2017. The main outcome was the risk of PH. The Cox proportional-hazards model and the Fine and Gray model were used to adjust covariate and competing risks to estimate the subdistribution hazard ratios (sHRs). 553,617 newly diagnosed COPD patients were stratified by statin users (n = 41,168) and statin nonusers (n = 512,449). After 1:1 propensity score matching of statin users (n = 41,163), and 41,163 statin nonusers were included for outcome analysis. Statin users had a 22% lower risk of PH than nonusers (sHR: 0.78, 95% confidence interval: 0.65-0.94). During subgroup analysis, taking higher daily doses and for a longer duration displayed a more significantly reduced risk of PH (both P for trend <0.001). Statins may have a protective effect against PH that is dose- and time-dependent.

Genipin attenuates hyperoxia-induced lung injury and pulmonary hypertension via targeting glycogen synthase kinase-3 ß in neonatal rats.

OBJECTIVES: Bronchopulmonary dysplasia is the most common chronic lung disease of infancy and is associated with pulmonary hypertension (PH). Inhibition of glycogen synthase kinase (GSK)-3 ß has been shown to attenuate lung injury and PH in hyperoxia-exposed newborn rats. Genipin has been widely used for the treatment of inflammatory diseases. The aim of this study was to show that genipin decreased the expression of GSK-3 ß in lung tissues of hyperoxia-exposed rat pups. METHODS: We established models of hyperoxia-exposed rat pups, evaluated lung injury and pulmonary hypertension and detected the mRNA and protein expression of key molecules. RESULTS: Hyperoxia resulted in the reduction of survival rate and histologic injury of lung tissues; an increase of the messenger RNA (mRNA) expression of transforming growth factor-ß1, extracellular matrix proteins collagen-I and fibronectin, and α-smooth muscle actin; an increase of right ventricular (RV) systolic pressure and the weight ratio of RV to left ventriclar (LV) plus septum (S) (RV/LV + S) were inhibited by genipin. Genipin also decreased the levels of tumor necrosis factor-α, interleukin-1 ß, and interleukin-6 in both bronchoalveolar lavage fluid and lung tissues after hyperoxia exposure. In addition, genipin inhibited p65 nuclear factor-κB nuclear translocation and matrix metalloproteinase-2 and -9 expression. Moreover, hyperoxia resulted in an increase of methane dicarboxylic aldehyde content and a decrease of superoxide dismutase activity, catalytic subunit of glutamate-cysteine ligase, modified subunit of glutamate-cysteine ligase, and nuclear factor erythroid 2-related factor 2 expression were inhibited by genipin. All these effects induced by genipin were blocked by upregulation of GSK-3 ß. Genipin downregulated GSK-3 ß expression, decreased nuclear factor-κB translocation, increased nuclear factor erythroid 2-related factor 2 expression, attenuated inflammation and oxidative stress, leading to amelioration of lung injury and PH in hyperoxia-exposed rat pups. CONCLUSION: Overall, genipin may provide a novel therapeutic option for preventing and treating infants with bronchopulmonary dysplasia.

Use of intravenous iron in cyanotic patients with congenital heart disease and/or pulmonary hypertension.

BACKGROUND: Secondary erythrocytosis is common in patients with cyanosis secondary to congenital heart disease (CHD) and/or pulmonary hypertension (PH). This compensatory mechanism aims at increasing oxygen delivery to the tissues, but it requires adequate iron stores. Optimal methods of iron supplementation in this setting remain controversial, with fears of excessive erythropoiesis and hyperviscosity symptoms. We describe our experience using intravenous ferrous carboxymaltose. METHODS AND RESULTS: 142 consecutive cyanotic patients were treated over 5.7 years (201 administrations). Mean age was 51.3 ±â€¯17.6 years and 55 (38.7%) were male. Eisenmenger syndrome (ES) was present in 41 (28.8%), other pulmonary arterial hypertension (PAH) related to CHD (PAH-CHD) in 27 (19.0%), cyanotic CHD without PAH in 16 (11.3%) and PH without CHD in 58(40.8%). Baseline haemoglobin (Hb) concentration was 14.6 ±â€¯3.0 g/dL and haematocrit 0.45 ±â€¯0.09. A 500 mg dose of intravenous (IV) iron carboxymaltose was given in 163 (81.1%) of administrations and a 1000 mg dose in 37 (18.4%). A significant improvement in average Hb, haematocrit, ferritin and transferrin saturation was observed after a median follow-up of 100.0 [70.0-161.0] days (p ≤ 0.0001 for all). There were no cases of excessive erythropoiesis resulting in new hyperviscosity symptoms and/or requiring venesection. A minor transient rash was observed in 2 patients and one patient experienced an air embolus causing a transient ischemic attack. CONCLUSIONS: Intravenous ferrous carboxymaltose appears to be safe in iron deficient patients with cyanosis due to CHD and/or PH, as long as care is taken to avoid air emboli. Further randomised studies are needed to confirm the safety and efficacy of intravenous iron in this setting.

Effect of electrical dyssynchrony on left and right ventricular mechanics in children with pulmonary arterial hypertension.

BACKGROUND: Electrical and right ventricular (RV) mechanical dyssynchrony has been previously described in pediatric pulmonary arterial hypertension (PAH), but less is known about the relationship between electrical dyssynchrony and biventricular function. In this study we applied cardiac magnetic resonance (CMR) imaging to evaluate biventricular size and function with a focus on left ventricular (LV) strain mechanics in pediatric PAH patients with and without electrical dyssynchrony. METHODS: Fifty-six children with PAH and comprehensive CMR evaluation were stratified based on QRS duration z-score, with electrical dyssynchrony defined as z-score ≥2. Comprehensive biventricular volumetric, dyssynchrony, and strain analysis was performed. RESULTS: Nineteen PAH patients had or developed electrical dyssynchrony. Patients with electrical dyssynchrony had significantly reduced RV ejection fraction (35% vs 50%, p = 0.003) and greater end-diastolic (168 vs 112 ml/m2, p = 0.041) and end-systolic (119 vs 57, ml/m2, p = 0.026) volumes. Patients with electrical dyssynchrony had reduced RV longitudinal strain (-14% vs -19%, p = 0.007), LV circumferential strain measured at the free wall (-19% vs -22%, p = 0.047), and the LV longitudinal strain in the septal region (-10% vs -15%, p = 0.0268). LV mechanical intraventricular dyssynchrony was reduced in patients with electrical dyssynchrony at the LV free wall (43 vs 19 ms, p = 0.019). CONCLUSIONS: The electrical dyssynchrony is associated with the reduced LV strain, enlarged RV volumes, and reduced biventricular function in children with PAH. CMR assessment of biventricular mechanical function with respect to QRS duration may help to detect pathophysiologic processes associated with progressed PAH.

PPARγ Alleviates Right Ventricular Failure Secondary to Pulmonary Arterial Hypertension in Rats.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling leading to right ventricular hypertrophy (RVH) and failure. Peroxisome proliferator-activated receptor γ (PPARγ), a member of nuclear receptors, has been proved to ameliorate PAH. However, its effect on PAH-induced right ventricular failure (RVF) remains unknown. Therefore, we investigated the therapeutic potential of PPARγ in preventing monocrotaline (MCT)-induced RV dysfunction. The PAH model was induced by MCT administration. Male rats were administered with MCT to develop PAH and RVF formed by approximately day 30. Significant increase in RV area, RVAW resulted in an ascending RV index. However, the LV function including EF, FS, and LVID did not change significantly. PPARγ agonist prevented PAH-induced RVF by preserving RV index and preventing RVH. PPARγ's beneficial effects seem to result from various factors, including anti-apoptosis, preservation RV index, reversal of inflammation, improvement of glucolipid metabolism, reduction of ROS. In a word, PPARγ agonist prevents the development of RVF.

Treatment strategies for the right heart in pulmonary hypertension.

The function of the right ventricle (RV) determines the prognosis of patients with pulmonary hypertension. While much progress has been made in the treatment of pulmonary hypertension, therapies for the RV are less well established. In this review of treatment strategies for the RV, first we focus on ways to reduce wall stress since this is the main determinant of changes to the ventricle. Secondly, we discuss treatment strategies targeting the detrimental consequences of increased RV wall stress. To reduce wall stress, afterload reduction is the essential. Additionally, preload to the ventricle can be reduced by diuretics, by atrial septostomy, and potentially by mechanical ventricular support. Secondary to ventricular wall stress, left-to-right asynchrony, altered myocardial energy metabolism, and neurohumoral activation will occur. These may be targeted by optimising RV contraction with pacing, by iron supplement, by angiogenesis and improving mitochondrial function, and by neurohumoral modulation, respectively. We conclude that several treatment strategies for the right heart are available; however, evidence is still limited and further research is needed before clinical application can be recommended.

Atrioventricular Node Dysfunction and Ion Channel Transcriptome in Pulmonary Hypertension.

BACKGROUND: Heart block is associated with pulmonary hypertension, and the aim of the study was to test the hypothesis that the heart block is the result of a change in the ion channel transcriptome of the atrioventricular (AV) node. METHODS AND RESULTS: The most commonly used animal model of pulmonary hypertension, the monocrotaline-injected rat, was used. The functional consequences of monocrotaline injection were determined by echocardiography, ECG recording, and electrophysiological experiments on the Langendorff-perfused heart and isolated AV node. The ion channel transcriptome was measured by quantitative PCR, and biophysically detailed computer modeling was used to explore the changes observed. After monocrotaline injection, echocardiography revealed the pattern of pulmonary artery blood flow characteristic of pulmonary hypertension and right-sided hypertrophy and failure; the Langendorff-perfused heart and isolated AV node revealed dysfunction of the AV node (eg, 50% incidence of heart block in isolated AV node); and quantitative PCR revealed a widespread downregulation of ion channel and related genes in the AV node (eg, >50% downregulation of Cav1.2/3 and HCN1/2/4 channels). Computer modeling predicted that the changes in the transcriptome if translated into protein and function would result in heart block. CONCLUSIONS: Pulmonary hypertension results in a derangement of the ion channel transcriptome in the AV node, and this is the likely cause of AV node dysfunction in this disease.

Simvastatin prevents and reverses chronic pulmonary hypertension in newborn rats via pleiotropic inhibition of RhoA signaling.

Chronic neonatal pulmonary hypertension (PHT) frequently results in early death. Systemically administered Rho-kinase (ROCK) inhibitors prevent and reverse chronic PHT in neonatal rats, but at the cost of severe adverse effects, including systemic hypotension and growth restriction. Simvastatin has pleiotropic inhibitory effects on isoprenoid intermediates that may limit activity of RhoA, which signals upstream of ROCK. We therefore hypothesized that statin treatment would safely limit pulmonary vascular RhoA activity and prevent and reverse experimental chronic neonatal PHT via downstream inhibitory effects on pathological ROCK activity. Sprague-Dawley rats in normoxia (room air) or moderate normobaric hypoxia (13% O2) received simvastatin (2 mg·kg-1·day-1 ip) or vehicle from postnatal days 1-14 (prevention protocol) or from days 14-21 (rescue protocol). Chronic hypoxia increased RhoA and ROCK activity in lung tissue. Simvastatin reduced lung content of the isoprenoid intermediate farnesyl pyrophosphate and decreased RhoA/ROCK signaling in the hypoxia-exposed lung. Preventive or rescue treatment of chronic hypoxia-exposed animals with simvastatin decreased pulmonary vascular resistance, right ventricular hypertrophy, and pulmonary arterial remodeling. Preventive simvastatin treatment improved weight gain, did not lower systemic blood pressure, and did not cause apparent toxic effects on skeletal muscle, liver or brain. Rescue therapy with simvastatin improved exercise capacity. We conclude that simvastatin limits RhoA/ROCK activity in the chronic hypoxia-exposed lung, thus preventing or ameliorating hemodynamic and structural markers of chronic PHT and improving long-term outcome, without causing adverse effects.

Hemodynamic assessment and acute pulmonary vasoreactivity testing in the evaluation of children with pulmonary vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

Invasive assessment of haemodynamics (ventricular, pulmonary) and testing of acute vasoreactivity in the catheterisation laboratory remain the gold standard for the diagnosis of pulmonary hypertension (PH) and pulmonary hypertensive vascular disease. However, these measurements and the interpretation thereof are challenging due to the heterogeneous aetiology of PH in childhood and potentially confounding factors in the catheterisation laboratory. Patients with pulmonary arterial hypertension (PAH) associated with congenital heart disease who have a cardiovascular shunt need to undergo a completely different catheterisation approach than those with idiopathic PAH lacking an anatomical cardiovascular defect. Diagnostic cardiac catheterisation of children with suspected PH usually includes right and left heart catheterisation, particularly for the initial assessment (ie, at the time of diagnosis), and should be performed in experienced centres only. Here, we present graded consensus recommendations for the invasive evaluation of children with PH including those with pulmonary hypertensive vascular disease and/or ventricular dysfunction. Based on the limited published studies and our own experience we suggest a structured catheterisation protocol and two separate definitions of positive acute vasoreactivity testing (AVT): (1) AVT to assess prognosis and indication for specific PH therapy, and (2) AVT to assess operability of PAH associated with congenital heart disease. The protocol and the latter definitions may help in the systematic assessment of these patients and the interpretation of the obtained data. Beyond an accurate diagnosis in the individual patient, such a structured approach may allow systematic decision making for the initiation of a specific treatment and may assist in estimating disease progression and individual prognosis.

Serum apelin as a novel non-invasive marker for subclinical cardiopulmonary complications in children and adolescents with sickle cell disease.

BACKGROUND: Cardiovascular involvement represents a leading cause of mortality and morbidity in sickle cell disease (SCD). Apelin is a peptide involved in the regulation of cardiovascular function. AIM: To determine serum apelin among 40 children and adolescents with SCD compared with 40 healthy controls and assess its relation to markers of hemolysis, iron overload as well as cardiopulmonary complications. METHODS: SCD patients, in steady state and asymptomatic for heart disease, were studied stressing on hydroxyurea/chelation therapy, hematological profile, serum ferritin and apelin levels. Full echocardiographic study including assessment of biventricular systolic function and pulmonary artery pressure was done. RESULTS: Apelin levels were significantly lower in SCD patients compared with controls (P<0.001). Cardiopulmonary complications were encountered in 30% of patients. Apelin was significantly decreased among patients with cardiopulmonary disease (P=0.006) whether those at risk of pulmonary hypertension (P=0.018) or patients with heart disease (P=0.043). Hydroxyurea-treated patients had higher apelin levels than untreated ones (P=0.001). Apelin was negatively correlated to lactate dehydrogenase, indirect bilirubin, serum ferritin, end systolic diameter, tricuspid regurgitant jet velocity, right ventricle systolic pressure, pulmonary vascular resistance and tissue Doppler imaging S wave. Apelin cutoff value of 1650ng/L could significantly detect the presence of cardiopulmonary complications in SCD with 90.9% sensitivity and 72.4% specificity. CONCLUSION: Apelin is a promising marker for screening of SCD patients at risk of cardiopulmonary disease because it is altered during the early subclinical stage of cardiac affection. A combination of apelin and echocardiography provides a reliable method to assess cardiopulmonary affection in young SCD patients.

[Efficacy Observation of Chinese Herbal Fumigation Combined Western Drugs for Treating Sys- temic Sclerosis Complicated Pulmonary Arterial Hypertension].

Objective To observe the therapeutic efficacy and safety of Chinese herbal fumigation combined with leflunomide (LEF) and prednisone (Pred) in treatment of systemic sclerosis (SSc) complicated pulmonary arterial hypertension (PAH). Methods Totally 99 SSc patients complicated early PAH were randomly assigned to the Western drugs group (WD, 49 cases) and the integrative medicine group (IM, 50 cases). Patients in the WD group took LEF (20 mg) and Pred (15 mg) , once per day. In addition to routine WD program, those in the IM group additionally received Chinese herbal fumigation. All treatment lasted for 6 months. Raynaud's phenomenon (RP) was observed in each group before and after treatment. RP score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), pulmonary arterial systolic pressure (PASP) , and pulmonary function were compared between the two groups before and after treatment. The clinical efficacy and adverse reactions were evaluated. Results Thirteen cases were lost due to various reasons. A total of 86 patients completed this study, 41 in the WD group and 45 in the IM group. Compared with the same group before treatment, RP score, levels of ESR and CRP all decreased in the two groups after treatment (P <0. 05). Compared with the WM group after treatment, RP score, levels of ESR and CRP were obviously lowered in the IM group after treatment (P < 0. 05). Besides, lowered differences between post-pre-values of ESR, CRP, and PASP were more obviously higher, while elevated differences between post-pre-values of total lung capacity (TLC) and carbon monoxide diffusing capacity (DLCO) were more obviously higher in the IM group (P <0. 05). The total effective rate was 93. 33% (42/45) in the IM group, obviously higher than that in the WD group [70. 73% (29/41) , P <0. 05 ]. There was no statistical difference in total adverse reaction rate between the two groups (x² =0. 019, P =0. 891). Conclusion Chinese herbal fumigation combined with WD had obvious efficacy with less adverse reactions, so it was worth clinical spread.

The potential of asiaticoside for TGF-ß1/Smad signaling inhibition in prevention and progression of hypoxia-induced pulmonary hypertension.

AIMS: Asiaticoside (AS) is a saponin monomer extracted from the medicinal plant Centella asiatica, which has a variety of biological effects. We intended to investigate the effects of asiaticoside on a hypoxia-induced pulmonary hypertension (HPH) rat model and examine the possible effects of asiaticoside on TGF-ß1/Smad signaling in vivo and in vitro. MAIN METHODS: The rat HPH model was established by hypoxic exposure and asiaticoside was administered for four weeks. Parameters including the mean pulmonary artery pressure (mPAP), the right ventricular hypertrophy (RVH) and the percentage of medial wall thickness were used to evaluate the development of HPH. TGF-ß1, TGF-ß receptor, Smad2/3 and phospho-Smad2/3 expressions were detected and the proliferation, migration and apoptosis of pulmonary arterial smooth muscle cells (PASMCs) adjusted by asiaticoside under the hypoxic condition were evaluated. KEY FINDINGS: Our data indicate that asiaticoside attenuated pulmonary hypertension, pulmonary vascular remodeling and RV hypertrophy in HPH rats, which was probably mediated by restraining the hypoxia-induced overactive TGF-ß1/Smad2/3 signaling and inhibiting the proliferation by inducing apoptosis of the PASMCs. SIGNIFICANCE: Given the preventative potential in animal models and in vitro, we propose asiaticoside as a promising protective treatment in HPH.

Inspiratory muscle training in pulmonary arterial hypertension.

PURPOSE: The purpose of this study was to investigate the effects of inspiratory muscle training (IMT) on functional capacity, respiratory muscle strength, pulmonary function, quality of life, and fatigue and dyspnea perception in patients with pulmonary arterial hypertension (PAH). METHODS: Twenty-nine clinically stable PAH patients were included in this study. These patients were randomly assigned to a 6-week IMT program (14 patients) or to a sham IMT protocol (15 patients). Before and after the treatment, pulmonary function, respiratory muscle strength, functional capacity, dyspnea and fatigue perception, and quality of life were evaluated. RESULTS: There were significant increases in maximal inspiratory and expiratory pressure, forced expiratory volume in 1 second (% predicted) and 6-minute walk distance in the IMT group compared with the control group (P < .05). There were significant decreases in the Fatigue Severity Scale score, Modified Medical Research Council dyspnea scores, and Nottingham Health Profile emotional reactions subscale in the IMT group compared with the control group (P < .05). CONCLUSIONS: Inspiratory muscle training promotes significant improvements in respiratory muscle strength and functional capacity, thus resulting in a reduction of dyspnea during activities of daily living and less fatigue in PAH patients. Inspiratory muscle training is a clinically practical treatment for PAH without any complications.

Soluble guanylate cyclase: a new therapeutic target for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Nitric oxide (NO) activates soluble guanylate cyclase (sGC) by binding its prosthetic heme group, thereby catalyzing cyclic guanosine monophosphate (cGMP) synthesis. cGMP causes vasodilation and may inhibit smooth muscle cell proliferation and platelet aggregation. The NO-sGC-cGMP pathway is disordered in pulmonary arterial hypertension (PAH), a syndrome in which pulmonary vascular obstruction, inflammation, thrombosis, and constriction ultimately lead to death from right heart failure. Expression of sGC is increased in PAH but its function is reduced by decreased NO bioavailability, sGC oxidation and the related loss of sGC's heme group. Two classes of sGC modulators offer promise in PAH. sGC stimulators (e.g., riociguat) require heme-containing sGC to catalyze cGMP production, whereas sGC activators (e.g., cinaciguat) activate heme-free sGC. Riociguat is approved for PAH and yields functional and hemodynamic benefits similar to other therapies. Its main serious adverse effect is dose-dependent hypotension. Riociguat is also approved for inoperable chronic thromboembolic pulmonary hypertension.