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Acta Physiologica Sinica ; (6): 503-511, 2023.
Article in Chinese | WPRIM | ID: wpr-1007765


In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.

Animals , Male , Rats , Caspase 3/metabolism , Collagen , Disease Models, Animal , Hypertension, Pulmonary/drug therapy , Monocrotaline/adverse effects , Panax notoginseng/chemistry , Proliferating Cell Nuclear Antigen/pharmacology , Pulmonary Arterial Hypertension , Pulmonary Artery/metabolism , Rats, Sprague-Dawley , Receptor, Notch3/genetics , RNA, Messenger , Saline Solution , Signal Transduction , Saponins/pharmacology
Acta Physiologica Sinica ; (6): 497-502, 2023.
Article in Chinese | WPRIM | ID: wpr-1007764


In this study, we used a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) to investigate the role and mechanism of angiotensin (Ang)-(1-7) in regulating pulmonary artery diastolic function. Three weeks after subcutaneous injection of MCT or normal saline, the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) of rats were detected using a right heart catheter. Vascular endothelium-dependent relaxation was evaluated by acetylcholine (ACh)-induced vasodilation. The relaxation function of vascular smooth muscle was evaluated by sodium nitroprusside (SNP)-induced vasodilation. Human pulmonary artery endothelial cells (HPAECs) were incubated with Ang-(1-7) to measure nitric oxide (NO) release levels. The results showed that compared with control rats, RVSP and RVHI were significantly increased in the MCT-PAH rats, and both ACh or SNP-induced vasodilation were worsened. Incubation of pulmonary artery of MCT-PAH rats with Ang-(1-7) (1 × 10-9-1 × 10-4 mol/L) caused significant vaso-relaxation. Pre-incubation of Ang-(1-7) in the pulmonary artery of MCT-PAH rats significantly improved ACh-induced endothelium-dependent relaxation, but had no significant effect on SNP-induced endothelium-independent relaxation. In addition, Ang-(1-7) treatment significantly increased NO levels in HPAECs. The Mas receptor antagonist A-779 inhibited the effects of Ang-(1-7) on endothelium-dependent relaxation and NO release from endothelial cells. The above results demonstrate that Ang-(1-7) promotes the release of NO from endothelial cells by activating Mas receptor, thereby improving the endothelium-dependent relaxation function of PAH pulmonary arteries.

Rats , Humans , Animals , Vasodilation , Pulmonary Arterial Hypertension , Monocrotaline/toxicity , Rats, Sprague-Dawley , Hypertension, Pulmonary/chemically induced , Endothelial Cells , Pulmonary Artery , Endothelium , Acetylcholine/pharmacology , Nitroprusside/pharmacology
Arch. argent. pediatr ; 120(6): e278-e282, dic. 2022. tab, ilus
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1399732


La displasia frontometafisaria 2 (DFM2) es una enfermedad rara causada por una mutación en el gen MAP3K7. En este artículo, se informa sobre un paciente de 7 años con DFM2 causada por una variante nueva de corte y empalme en MAP3K7. El paciente presenta las características frecuentes de la DFM2, pero algunas nunca antes informadas. No se dispone de una descripción sistemática de las características de las imágenes tomográficas de la DFM2. Describimos ciertas diferencias en las características de la DFM2, la bibliografía publicada y las manifestaciones imagenológicas generales de la DFM2. Este caso resalta la importancia del valor clínico de la tomografía computada (TC) y la renderización de volúmenes (VR) en el diagnóstico de la DFM2. Las características de la DFM2 pueden observarse claramente en los estudios tomográficos, lo que señala la gran importancia de la TC para el diagnóstico y el tratamiento precoces de los pacientes con DFM2.

Frontometaphyseal dysplasia 2 (FMD2) is a rare disease caused by MAP3K7 gene mutation. We report a 7-year-old sporadic patient with FMD2 due to a de novo splicing variant in MAP3K7. He has the common characteristics of FMD2 but also has some characteristics that have never been reported, which increases the clinical phenotype of FMD2. Moreover, no systematic description of the imaging characteristics of FMD2 in computed tomography (CT) is available. In the present work, we found some different features of FMD2, reviewed previous literature, and summarized the general imaging manifestations of FMD2. This case emphasizes the important clinical value of CT and VR in the diagnosis of FMD2. We can clearly find the characteristics of FMD2 by CT examination, indicating its great significance for the prompt diagnosis and treatment of FMD2 patients.

Humans , Male , Child , Osteochondrodysplasias/complications , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/genetics , Pulmonary Arterial Hypertension , Phenotype , Forehead
São Paulo med. j ; 140(3): 505-508, May-June 2022. tab, graf
Article in English | LILACS | ID: biblio-1377380


ABSTRACT BACKGROUND: Severe pulmonary arterial hypertension (PAH) is a contraindication for heart transplantation (HT). It has been correlated with increased early and late mortality, mainly associated with right ventricular failure. Ventricular assistance devices (VADs) can promote reduction of intracardiac pressures and consequent reduction of PAH over the medium and long terms, thus enabling future candidature for HT. The diminution of early pulmonary pressure within this scenario remains unclear. OBJECTIVE: To evaluate the reduction of PAH and correlate data from right catheterization with the earliness of this reduction. DESIGN AND SETTING: Cross-sectional study in a general hospital in São Paulo, Brazil. METHODS: This was a retrospective analysis on the medical records of patients undergoing VAD implantation in a single hospital. Patients for whom VAD had been indicated as a bridge to candidature for HT due to their condition of constant PAH were selected. RESULTS: Four patients with VADs had constantly severe PAH. Their mean pulmonary artery systolic pressure (PASP) before VAD implantation was 66 mmHg. Over the 30-day period after the procedure, all the patients evolved with a drop in PASP to below 60 mmHg. Their new average was 36 mmHg, which was a drop of close to 50% from baseline values. The one-year survival of this sample was 100%. CONCLUSION: VAD implantation can reduce PAH levels. Early reduction occurred in all patients. Thus, use of VAD is an important bridge tool for enabling candidature for HT among patients with constantly severe PAH.

Humans , Pulmonary Arterial Hypertension/surgery , Hypertension, Pulmonary/surgery , Pulmonary Artery , Brazil , Cross-Sectional Studies , Retrospective Studies
Philippine Journal of Internal Medicine ; : 49-53, 2022.
Article in English | WPRIM | ID: wpr-960163


@#<p style="text-align: justify;"><strong>Background:</strong> Human Immunodeficiency Virus (HIV) infection can be complicated by pulmonary arterial hypertension (PAH-HIV) wherein it can occur in approximately 0.5% of HIV patients. The benefit of ART in treating PAH-HIV is unclear in this population. Data on its safety, efficacy, and effect on the progression of PAH are conflicting and limited. In this case report, improvement in PAH was noted after ART was started.</p><p style="text-align: justify;"><strong>Case:</strong> A 43-year-old, male, patient with no comorbidities, consulted due to a five-month history of progressive dyspnea, body malaise as well as weight loss. The patient is heterosexual with multiple sexual partners, an injection drug user, and was previously worked up for HIV, Hepatitis B, and C with unremarkable results. Initially managed as a case of Pneumonia but on CT scan was found to have a suprahilar mass which showed chronic granulomatous features. The positive GeneXpert confirms Pulmonary Tuberculosis (PTB). However, dyspnea was noted to progress thus 2D echocardiography was done which revealed severe pulmonary arterial hypertension with normal left ventricular function. Rescreening for HIV turned out positive thus started on anti-retroviral therapy (ART) with a noted improvement of symptoms as well as improvement and eventual normalization in pulmonary artery pressure. One year after initial diagnosis, undetectable viral load for HIV and Hepatitis C were noted along with improvement in CD4 count.</p><p style="text-align: justify;"><strong>Conclusion:</strong> This is a rare case of severe pulmonary hypertension as an initial presentation for HIV infection. The approach to patients with incidental PAH may include work-up for HIV especially when risk factors are present. ART treatment may provide a favorable therapeutic option if initiated early.</p>

Pulmonary Arterial Hypertension , HIV , Tuberculosis, Pulmonary
Article in Portuguese | LILACS, CONASS, ColecionaSUS, SES-GO | ID: biblio-1391794


Selexipague e outros medicamentos de controle da Hipertensão Arterial Pulmonar grupo 1. Indicação: Tratamento de Hipertensão Arterial Pulmonar grupo 1. Pergunta: Há superioridade em eficácia e segurança da tripla terapia com selexipague, comparado a dupla terapia, disponível no SUS, no tratamento de Hipertensão Arterial Pulmonar grupo 1? Métodos: Revisão rápida de evidências (overview) de ensaios clínicos randomizados e revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada pela ferramenta risco de viés da Cochrane. Resultados: Foi selecionado um ensaio clínico randomizado, especificamente um artigo contendo análise de subgrupo de dados desse estudo. Conclusão: As evidências demonstraram redução do número de hospitalizações relacionadas à HAP e de eventos de progressão da doença no tratamento de selexipague em tripla terapia em pacientes na classe funcional II, quando comparada à dupla terapia sem selexipague. A tripla terapia é tão segura quanto a dupla terapia, pois tem riscos similares de eventos adversos e eventos adversos sérios. A tripla terapia não é diferente da dupla terapia no risco da mortalidade geral

Selexipag and other drugs for the control of Pulmonary Arterial Hypertension group 1. Indication: Treatment of Pulmonary Arterial Hypertension group 1. Question: Is there superiority in efficacy and safety of triple therapy with selexipag, compared to dual therapy, available in the SUS, in the treatment of ulmonary Arterial Hypertension group 1? Methods: Rapid review of evidence (overview) of randomized clinical trials and systematic reviews, with a bibliographic survey carried out in the PUBMED database, using a structured search strategy. Results: A randomized clinical trial was selected, specifically an article showing a subgroup analysis of data from this study. Conclusion: Evidence showed a reduction in the number of Pulmonary Arterial Hypertension related hospitalizations and disease progression events in the treatment of selexipag in triple therapy in patients in functional class II, when compared to dual therapy without selexipag. Triple therapy is as safe as dual therapy, as it has similar risks of adverse events and serious adverse events. Triple therapy is no different from dual therapy in the risk of overall mortality

Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Pyrazines/administration & dosage , Pulmonary Arterial Hypertension/drug therapy , Acetamides/administration & dosage , Antihypertensive Agents/administration & dosage , Randomized Controlled Trials as Topic , Treatment Outcome , Systematic Reviews as Topic
Chinese Journal of Cardiology ; (12): 282-288, 2022.
Article in Chinese | WPRIM | ID: wpr-935141


Objective: To explore the impact of composite clinical worsening (cCW) events and its components on the prognosis of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH). Methods: This is a retrospective study. Patients who were diagnosed with CHD-PAH in Beijing Anzhen Hospital between January 2007 and July 2018, were included, and their baseline clinical data including demographic, clinical manifestations and New York Heart Association (NYHA) classification were collected retrospectively. All-cause deaths and clinical worsening events were recorded, which included syncope, PAH related hospitalization, NYHA classification deterioration and ≥ 2 PAH related clinical symptoms (dyspnea, hemoptysis, edema, chest pain, palpitations, cyanosis) appearance/progress. Three kinds of cCW events were defined: cCW1 (included PAH related hospitalization, NYHA classification deterioration), cCW2 (increased syncope on the basis of cCW1) and cCW3 (increased ≥ 2 PAH related clinical symptoms appearance/progress on the basis of cCW2). The Kaplan-Meier survival curve was used to analyze the long-term survival of the included patients. Univariate and multivariate Cox regression models were used to evaluate the impact of cCW events and their components on the risk of all-cause mortality. Results: A total of 525 patients with CHD-PAH were included in this study. The median age at diagnosis was 20.7 (11.2, 30.3) years. There were 43.8% children (<18 years), and 68.8% female patients. There were 431 patients (82.1%) with NYHA classification II. A total of 180 patients had PAH symptoms at diagnosis. The median follow-up time was 4.5 (2.6, 6.7) years. Forty-seven patients (9.0%) died during the follow-up period. Survival rates at 1, 5 and 10 years after diagnosis of PAH were 98.0%, 89.9% and 84.4%, respectively. Cox multivariate analysis showed that NYHA classification deterioration (HR=3.901, 95%CI 1.863-8.169, P<0.001), ≥2 PAH symptoms appearance/progress (HR=4.458, 95%CI 1.870-10.625, P<0.001), PAH-related hospitalization (HR=4.058, 95%CI 1.851-8.896, P<0.001) and syncope (HR=11.313, 95%CI 4.860-26.332, P<0.001) were independent predictors of increased risk of death. All 3 kinds of cCW events were significantly associated with the significantly increased risk of death, and cCW2 was highly predictive to increased risk of death (HR=15.476, 95%CI 4.346-37.576, P<0.001). Conclusions: The overall long-term prognosis of CHD-PAH patients in this study is relatively good. cCW events and its components (NYHA classification deterioration, ≥2 PAH symptoms occurrence/worsening, PAH-related hospitalization and syncope) have adverse influence on all-cause death in this patient cohort.

Child , Female , Humans , Male , Familial Primary Pulmonary Hypertension/complications , Heart Defects, Congenital/complications , Hypertension, Pulmonary/complications , Pulmonary Arterial Hypertension , Retrospective Studies
Chinese Journal of Cardiology ; (12): 166-171, 2022.
Article in Chinese | WPRIM | ID: wpr-935122


Objective: To explore the short-term efficacy of fenestrated atrial septal defect (ASD) occulders in the treatment of pulmonary arterial hypertension (PAH). Methods: Thirty-six healthy dogs were divided into the balloon atrial septostomy (BAS)+fenestrated ASD occulders group (n=12), BAS group (n=12) and non-septostomy group (n=12). PAH was induced by intra-atrial injection of dehydrogenized monocrotaline (1.5 mg/kg) in all dogs. Animals in the BAS+fenestrated ASD occulders group underwent atrial septal puncture and fenestrated ASD occulders implantation. Animals in the BAS group underwent balloon atrial septostomy. The non-septostomy group received no surgical intervention. The hemodynamic indexes and blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) of dogs were measured before modeling, 2 months after modeling, 1, 3, and 6 months after surgery, respectively. Echocardiography was performed to observe the patency of the shunt and atrial septostomy of the dogs in the BAS+fenestrated ASD occulders group and BAS group at 1, 3, and 6 months after surgery. Three dogs were sacrificed in each group at 1, 3, and 6 months after surgery, respectively. Atrial septal tissue and fenestrated ASD occulders were removed to observe the patency and endothelialization of the device. Lung tissues were obtained for hematoxylin-eosin (HE) staining to observe the inflammatory cells infiltration and the thickening and narrowing of the pulmonary arterials. Results: Among 36 dogs, 2 dogs died within 24 hours after modeling, and 34 dogs were assigned to BAS+fenestrated ASD occulders group (n=12), BAS group (n=11), and non-septostomy group (n=11). Compared with BAS group, the average right atrial pressure (mRAP) and NT-proBNP of dogs in the BAS+fenestrated ASD occulders group were significantly reduced at 3 months after surgery (P<0.05), and the cardiac output (CO) was significantly increased at 6 months after surgery, arterial oxygen saturation (SaO2) was also significantly reduced (P<0.05). Compared with non-septostomy group, dogs in the BAS+fenestrated ASD occulders group had significantly lower mRAP and NT-proBNP at 1, 3, and 6 months after surgery (P<0.05), and higher CO and lower SaO2 at 6 months after surgery (P<0.05). Compared with the non-septostomy group, the dogs in the BAS group had significantly lower mRAP and NT-proBNP at 1 month after surgery (P<0.05), and there was no significant difference on mRAP and NT-proBNP at 3 and 6 months after surgery (P>0.05). Echocardiography showed that there was a minimal right-to-left shunt in the atrial septum in the BAS group at 1 month after the surgery, and the ostomy was closed in all the dogs in the BAS group at 3 months after the surgery. There was still a clear right-to-left shunt in the dogs of BAS+fenestrated ASD occulders group. The shunt was well formed and satisfactory endothelialization was observed at 1, 3 and 6 months after surgery. The results of HE staining showed that the pulmonary arterials were significantly thickened, stenosis and collapse occurred in the non-septostomy group. Pulmonary microvascular stenosis and inflammatory cell infiltration in the pulmonary arterials were observed in the non-septostomy group. Pulmonary arterial histological results were comparable between BAS+fenestrated ASD occulders group and non-septostomy group at 6 months after surgery . Conclusions: The fenestrated ASD occulder has the advantage of maintaining the open fistula hole for a longer time compared with simple balloon dilation. The fenestrated ASD occulder can improve cardiac function, and it is safe and feasible to treat PAH in this animal model.

Animals , Dogs , Atrial Septum/surgery , Cardiac Catheterization/methods , Familial Primary Pulmonary Hypertension , Heart Septal Defects, Atrial/surgery , Hypertension, Pulmonary , Pulmonary Arterial Hypertension
Rev. Méd. Inst. Mex. Seguro Soc ; 60(1): 67-74, 2022. tab, graf
Article in Spanish | LILACS | ID: biblio-1361391


Se presenta un modelo departamental para la atención integral de pacientes con hipertensión pulmonar. Se resume el conocimiento actual de la hipertensión pulmonar, su mortalidad, pronóstico y la estratificación de su severidad que justifican la propuesta de la estructura y la función departamental.

A departmental model for the comprehensive care of patients with pulmonary hypertension is presented. The current knowledge of pulmonary hypertension, its mortality, prognosis and the stratification of its severity that justify the proposal of the departmental structure and function are summarized.

Humans , Comprehensive Health Care/organization & administration , Hospital Departments/organization & administration , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/therapy , Prognosis , Severity of Illness Index , Risk Assessment , Pulmonary Arterial Hypertension/diagnosis , Pulmonary Arterial Hypertension/mortality , Pulmonary Arterial Hypertension/therapy , Hypertension, Pulmonary/epidemiology
Rev. medica electron ; 43(6): 1606-1616, dic. 2021.
Article in Spanish | LILACS, CUMED | ID: biblio-1409668


RESUMEN Introducción: la adherencia terapéutica es un problema multifactorial que ha generado el interés de muchos investigadores a nivel mundial. Objetivo: determinar la adherencia al tratamiento antihipertensivo en pacientes adultos mayores y los factores asociados a la no adherencia. Materiales y métodos: se realizó un estudio descriptivo longitudinal en pacientes adultos mayores hipertensos, pertenecientes al Policlínico Comunitario Sur, del municipio Morón, en la provincia de Ciego de Ávila. La adherencia al tratamiento fue evaluada por el cuestionario Martín-Bayarre-Grau y el nivel de conocimiento de la enfermedad por el Test de Batalla. Se identificaron las causas asociadas a los problemas de adherencia en dichos pacientes. Resultados: Predominó la no adherencia al tratamiento antihipertensivo en un 62 %. La adherencia parcial se constató en un 22 %. Los problemas de adherencia prevalecieron en las féminas de 60-69 años de edad. Se detectaron múltiples causas inherentes al paciente, como el olvido (48,4 %), la no disponibilidad de medicamentos (25,8 %) y el alivio de los síntomas (16,1 %). Entre otras causas se detectó el bajo nivel de conocimiento de la enfermedad y la presencia de comorbilidades. Conclusiones: se evidenció un predominio de adherencia al tratamiento antihipertensivo de los adultos mayores. Sus causas fundamentales fueron el olvido de ingerir el medicamento, la no disponibilidad de medicamentos, la falta de conocimientos sobre la enfermedad y la presencia de comorbilidades (AU).

ABSTRACT Introduction: therapeutic adherence is a multifactorial problem that has generated the interest of many researchers worldwide. Objective: to determine adherence to antihypertensive therapy in older adult patients and the factors associated with no adherence. Materials and methods: a longitudinal descriptive study was carried out in hypertensive elderly patients belonging to the South Community Polyclinic, in the municipality of Moron, in the province of Ciego de Avila. The adherence to treatment was evaluated by the Martín-Bayarre-Grau questionnaire and the level of knowledge of the disease by the Batalla test. The causes associated with adherence problems in these patients were identified. Results: non-adherence to antihypertensive therapy predominated in 62%. Partial adherence was found to be 22%. Adherence problems prevailed in women aged 60-69 years. Multiple causes related with the patient were detected, such as forgetfulness (48.4%), non-availability of medicines (25.8%) and relief of symptoms (16.1%). Among other causes, the low level of knowledge on the disease and the presence of comorbidities were detected. Conclusions: a predominance of adherence to antihypertensive treatment in older adults was evidenced. Its main causes were the forgetfulness of taking the medicine, the non-availability of medicines, the lack of knowledge about the disease and the presence of comorbidities (AU).

Humans , Male , Female , Aged , Pulmonary Arterial Hypertension/drug therapy , Risk Factors , Patient Compliance , Treatment Adherence and Compliance , Pulmonary Arterial Hypertension/diagnosis , Pulmonary Arterial Hypertension/mortality , Pulmonary Arterial Hypertension/epidemiology
Arq. bras. cardiol ; 117(4): 750-764, Oct. 2021. tab, graf
Article in Portuguese | LILACS | ID: biblio-1345224


Resumo Muitos avanços ocorreram nas últimas décadas na terapêutica da hipertensão arterial pulmonar (HAP), uma doença grave, progressiva, incurável e potencialmente fatal. Para seu tratamento adequado, são fundamentais o diagnóstico hemodinâmico e a classificação de sua etiologia, em que várias delas (colagenoses, hipertensão portal, cardiopatia congênitas, esquistossomose) requerem medidas específicas, além do tratamento farmacológico característico para HAP. O tratamento com fármacos-alvo para HAP baseia-se em produtos farmacêuticos que interferem em três vias fisiopatológicas moleculares: da prostaciclina, da endotelina e do óxido nítrico. Tais fármacos apresentam múltiplas apresentações (oral, endovenosa, subcutânea e inalatória) e mudaram a história da HAP. Essas medicações e suas estratégias de uso, assim como particularidades das diferentes formas de HAP, são o foco desta revisão.

Abstract In the last decades, important advances have been made in the treatment of pulmonary arterial hypertension (PAH), a severe, progressive, incurable, and potentially fatal disease. For an adequate therapy, correct hemodynamic diagnosis and etiology classification are fundamental. Many etiologies - rheumatic disease, portal hypertension, congenital heart diseases, schistosomiasis - require specific measures, in addition to drug therapy for PAH. The specific therapy for PAH is based on medications that act on three pathophysiological pathways - prostacyclin, endothelin, and nitric oxide pathways. These drugs have multiple presentations (oral, intravenous, subcutaneous, and inhaled) and have changed the history of PAH. This review presents an overview of drug therapy strategies and different forms and peculiarities of PAH.

Humans , Pulmonary Arterial Hypertension , Hypertension, Pulmonary/drug therapy , Hemodynamics
Rev. Assoc. Med. Bras. (1992) ; 67(10): 1437-1442, Oct. 2021. tab, graf
Article in English | LILACS | ID: biblio-1351424


SUMMARY OBJECTIVE: Oxidative stress plays a pivotal role in the pathogenesis of pulmonary arterial hypertension. 8-Hydroxy-2'-deoxyguanosine is a sensitive biomarker that reflects the degree of oxidative damage to DNA. We investigated whether serum 8-Hydroxy-2'-deoxyguanosine is a clinically useful biomarker for the severity of pulmonary arterial hypertension. METHODS: We measured serum 8-Hydroxy-2'-deoxyguanosine levels in 25 patients (age 37±13 years, 68% women) diagnosed with idiopathic pulmonary arterial hypertension, familial pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease. The severity of pulmonary arterial hypertension was evaluated by six-min walking distance, World Health Organization functional class, and serum brain natriuretic peptide levels. Age and gender-matched 22 healthy subjects served as the control group. RESULTS: The comparison of 8-Hydroxy-2'-deoxyguanosine levels between patients and controls was not statistically different [(19.86±9.79) versus (18.80±3.94) ng/mL, p=0.622)]. However, there was a significant negative correlation between 8-Hydroxy-2'-deoxyguanosine levels and six-min walking distance (r= −0.614, p=0.001). Additionally, serum 8-Hydroxy-2'-deoxyguanosine levels in patients with functional class III-IV were significantly higher than those with functional class I-II (functional class III-IV 32.31±10.63 ng/mL versus functional class I-II 16.74±6.81 ng/mL, respectively, p=0.003). CONCLUSION: The 8-Hydroxy-2'-deoxyguanosine levels were significantly correlated with exercise capacity (six-min walking distance) and symptomatic status (functional class), both of which show the severity of pulmonary arterial hypertension in patients.

Humans , Male , Adult , Young Adult , Pulmonary Arterial Hypertension , Hypertension , Oxidative Stress , Familial Primary Pulmonary Hypertension , Middle Aged
Medicina (B.Aires) ; 81(4): 624-636, ago. 2021. graf
Article in Spanish | LILACS | ID: biblio-1346516


Resumen La hipertensión arterial pulmonar (HAP) requiere procesos estructurados de diagnóstico y estratificación de riesgo, siendo la función del ventrículo derecho (VD) un marcador pronóstico central. Los principales objetivos terapéuticos en la HAP son mejorar y/o intentar revertir la disfunción del VD y mantener condición de bajo riesgo. Actualmente existen múltiples fármacos con diferentes mecanismos de acción cuya combinación en doble o triple terapia ha mostrado mejores resultados que la monoterapia. Evidencia actual demuestra la importancia de incorporar tempranamente prostanoides parenterales al esquema, mejorando la funcionalidad del VD y la supervivencia. En esta revisión se refleja el papel de la función del VD en el diagnós tico, pronóstico y seguimiento de la HAP. Se recomienda la evaluación sistemática y estandarizada del VD, así como el inicio temprano de tratamiento combinado en riesgo intermedio-alto para obtener las metas de alcanzar y mantener un riesgo bajo y/o evitar la progresión de la HAP.

Abstract Pulmonary arterial hypertension (PAH) requires structured processes of diagnosis and risk stratifica tion, being the function of the right ventricle (RV) a hallmark prognosis determinant. The main therapeutic goals in PAH are to improve and try to revert RV dysfunction and maintaining a low risk. Currently, there are multiple treatments with different mechanisms of action, the combination of which in double or triple therapy has shown improved results compared to monotherapy. Recent clinical evidence shows the importance of early incorpora tion of parenteral prostanoids to the scheme, improving RV function and survival. In this review, we discuss the role of the RV function in the diagnosis, prognosis, and follow-up of PAH. We recommend the systematic and standardised evaluation of the RV as well as the early initiation of combined treatment in cases of intermediate-high risk to try to reach and keep the patient with PAH at a low risk and / or avoid the progression of PAH.

Humans , Ventricular Dysfunction, Right , Pulmonary Arterial Hypertension , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/drug therapy , Ventricular Function, Right , Heart Ventricles/diagnostic imaging
Rev. chil. enferm. respir ; 37(2): 115-124, jun. 2021. ilus, tab
Article in Spanish | LILACS | ID: biblio-1388140


Resumen La prueba de velocidad de marcha en 4 metros (T4M) es considerada sustituto de la caminata en 6 min (TC6M) en EPOC. Sin embargo, no ha sido bien investigada en otras enfermedades respiratorias. Durante un año estudiamos pacientes que concurrieron a nuestra Unidad para realizar el TC6M midiendo la velocidad alcanzada en 4 metros, 2 h previo a realizar el TC6M. De 162 pacientes 99 eran mujeres. La edad media fue de 65 años, peso de 73 kg, talla de 158 cm, IMC 29,4 kg/m2. 36% tenían fibrosis pulmonar idiopática, 17% EPOC, GOLD IV,11% EPOC, GOLD III, 12% apnea de sueño y 12% otras enfermedades. No hubo diferencia para los distintos diagnósticos en ambos tests. La distancia media en TC6Mfue 368,5 m la velocidad: 1,01 m/s en T4M.Hubo una correlación positiva significativa entre ambos test: alto rendimiento en T4M es equivalente a un alto rendimiento en el TC6M. Hubo correlación negativa con la edad y positiva con la estatura. Al año de seguimiento 16 pacientes habían fallecido, siendo estos los que habían obtenido los más bajos rendimientos en ambos tests (T4M: 0,69 m/s y 248,1 m en TC6M) La posibilidad de sobrevida cayó a 20% en aquellos individuos que alcanzaron una velocidad inferior a 0,69 m/s. Es posible sustituir el TC6M por el T4M en pacientes con diferentes patologías respiratoria, podemos predecir la muerte por cualquier causa si un sujeto camina a una velocidad ≤ 0,69 m/s, T4M es barato y fácil de realizar en atención primaria, sirviendo como evaluación de riesgo para referir a un centro más complejo.

4-Meter Gait Speed Test (4MGST) a frailty test, is considered a surrogate for the 6-Minute Walk Test (6MWT) in COPD. However, it has not been investigated in other respiratory conditions. Over a year, we studied patients attending our Unit for evaluation with 6MWT, measuring the speed they achieved walking 4 m, 2 h before performing 6MWT. 162 patients (99 women) were studied; series' mean values were: age 65 years-old; body weight, 73 kg; height, 158 cm and BMI, 29.4 kg/m2. 36% of them had idiopathic pulmonary fibrosis, 17% GOLD IV COPD, 11% GOLD III COPD, 12% pulmonary arterial hypertension, 12% obstructive apnea-hypopnea syndrome, and 12% other conditions. ANOVA showed no difference between diagnostic categories for both test. Average score in 6MWT was 368.5 m and 1.01 m/s in 4MGST. Pearson correlation coefficient revealed significant positive correlation between results of both tests: high score in 4MGST is equivalent to high score in 6MWT. There was negative correlation with age and positive correlation with height. At one year follow-up, 16 patients had died. They obtained significantly lower scores in both tests (4MGST: 0.69 m/s and 6MWT: 248.1 m) Survival chance fell to 20% for patients walking slower than 0.69 m/s. It is possible to replace TC6M with T4M in patients with different respiratory pathologies, we can predict death for any cause if a subject walked at ≤ speed at 0.69 m/s. T4M is cheap and easy to perform in primary care, serving as a risk assessment to refer to a more complex center.

Humans , Male , Female , Middle Aged , Aged , Primary Health Care , Respiratory Tract Diseases/physiopathology , Walk Test , Respiratory Tract Diseases/mortality , Survival Analysis , Chronic Disease , Pulmonary Disease, Chronic Obstructive , Idiopathic Pulmonary Fibrosis , Walking Speed , Pulmonary Arterial Hypertension
São Paulo med. j ; 139(5): 505-510, May 2021. tab
Article in English | LILACS | ID: biblio-1290253


ABSTRACT BACKGROUND: The mechanism of exercise limitation in idiopathic pulmonary arterial hypertension (IPAH) is not fully understood. The role of hemodynamic alterations is well recognized, but mechanical, ventilatory and gasometric factors may also contribute to reduction of exercise capacity in these individuals. OBJECTIVE: To investigate whether there is an association between ventilatory pattern and stress Doppler echocardiography (SDE) variables in IPAH patients. DESIGN AND SETTING: Single-center prospective study conducted in a Brazilian university hospital. METHODS: We included 14 stable IPAH patients and 14 age and sex-matched controls. Volumetric capnography (VCap), spirometry, six-minute walk test and SDE were performed on both the patients and the control subjects. Arterial blood gases were collected only from the patients. The IPAH patients and control subjects were compared with regard to the abovementioned variables. RESULTS: The mean age of the patients was 38.4 years, and 78.6% were women. The patients showed hypocapnia, and in spirometry 42.9% presented forced vital capacity (FVC) below the lower limit of normality. In VCap, IPAH patients had higher respiratory rates (RR) and lower elimination of CO2 in each breath. There was a significant correlation between reduced FVC and the magnitude of increases in tricuspid regurgitation velocity (TRV). In IPAH patients, VCap showed similar tidal volumes and a higher RR, which at least partially explained the hypocapnia. CONCLUSIONS: The patients with IPAH showed hypocapnia, probably related to their higher respiratory rate with preserved tidal volumes; FVC was reduced and this reduction was positively correlated with cardiac output.

Humans , Female , Adult , Pulmonary Arterial Hypertension , Cross-Sectional Studies , Prospective Studies , Echocardiography, Stress , Exercise Test , Familial Primary Pulmonary Hypertension , Lung/diagnostic imaging
Rev. cuba. anestesiol. reanim ; 20(1): e656, ene.-abr. 2021. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1156370


Introducción: La hipertensión arterial pulmonar es una enfermedad con una baja incidencia en la gestante, aunque trae consigo una alta mortalidad una vez presentada. Un diagnóstico oportuno y un manejo perioperatorio adecuado minimizan el riesgo de desenlace fatal tanto para la madre como el feto. Objetivo: Describir el comportamiento de la hipertensión arterial pulmonar en la gestante a término y su conducción anestésica. Presentación del caso: Paciente de 23 años, antecedentes de salud, edad gestacional de 35.2 semanas. Luego de presentar dolor de espalda y ardor en el pecho relacionado con el esfuerzo, palpitaciones, disnea y bloqueo de rama derecha en electrocardiograma, se ingresa en UTI con sospecha de tromboembolismo pulmonar, el cual queda descartado tras diagnóstico confirmatorio de hipertensión pulmonar después de realizar angio TAC y ecocardiografía. Se decide realizar cesárea programada bajo técnica regional peridural, sin complicaciones tanto para la madre como el niño. Después de 2 días bajo vigilancia intensiva se traslada a su centro hospitalario de cabecera. Conclusiones: La vía del parto, así como una elección adecuada de la técnica anestésica, puede ser la diferencia entre el éxito y la fatalidad. Las técnicas regionales suelen recomendarse por encima de la técnica de anestesia general siempre que no se presenten contraindicaciones(AU)

Introduction: Pulmonary arterial hypertension is a disease with low incidence in the pregnant woman, although it brings about high mortality once presented. Timely diagnosis and adequate perioeprative management minimize the risk of fatal outcome for both mother and fetus. Objective: To describe pulmonary arterial hypertension and its anesthetic management in the term pregnant woman. Case presentation: 23-year-old female patient, with health history and gestational age of 35.2 weeks. After presenting back pain and chest burning associated with exertion, palpitations, dyspnea and right bundle branch block in the electrocardiogram, the patient was admitted to the intensive care unit with suspected pulmonary thromboembolism, which was ruled out due to the confirmatory diagnosis of pulmonary hypertension after performing computerized tomography angiography and echocardiography. Scheduled cesarean section was decided to be perform using the regional peridural technique, without complications for both the mother and the child. After two days under intensive surveillance, she was transferred to her primary hospital. Conclusions: The route of delivery, as well as an adequate choice of the anesthetic technique, can be the difference between success and fatality. Regional techniques are usually recommended over the general anesthesia technique, as long as there are no contraindications(AU)

Humans , Female , Pregnancy , Young Adult , Echocardiography/methods , Gestational Age , Pulmonary Arterial Hypertension/complications , Pulmonary Arterial Hypertension/diagnostic imaging , Anesthesia, General/methods , Pregnancy Complications/prevention & control , Cesarean Section/methods
Article in Portuguese | LILACS | ID: biblio-1177060


Introdução: as cardiopatias congênitas são classificadas como um dos principais grupos para desenvolver hipertensão arterial pulmonar. O programa de exercício físico pode auxiliar no aumento da capacidade de vida diária, melhora clínica e funcional, minimizando as consequências deletérias da patologia. Relato do caso: reportamos um caso de um paciente do gênero masculino, 31 anos, com diagnóstico clínico de hipertensão arterial pulmonar grave em decorrência da dupla via de saída do ventrículo direito com comunicação interventricular, sem intervenção cirúrgica. Após ser encaminhado ao programa de Reabilitação Cardiopulmonar e Metabólica em um centro de referência em cardiologia do Rio Grande do Sul, foram realizadas avaliações clínicas e, também, da capacidade funcional pelo teste de caminhada de 6 minutos, da força muscular e resistência periférica, pelo teste Sentar-Levantar, e da força muscular respiratória, pelo exame de manovacuometria. Os valores apresentavam-se abaixo do valor previsto. O programa de exercício proposto foi realizado durante 30 sessões constando de exercícios aeróbicos com duração de 33 minutos, combinados ao treino de fortalecimento dos grandes grupos musculares. Conclusão: após o término do programa observou-se um acréscimo de 83 metros no teste de caminhada de 6 minutos e um aumento da força muscular respiratória, assim como, redução redução nos parâmetros da escala de Borg.

Introduction: congenital heart disease is classified as one of the main groups to develop pulmonary arterial hypertension. The exercise program can help to improve daily living, capacity, clinical and functional improvement, minimizing the deleterious consequences of the disease. Case report: we report a case of a 31-year-old male patient with a clinical diagnosis of severe pulmonary arterial hypertension due to the right ventricular double outflow tract with interventricular communication without surgical intervention. After being referred to the Cardiopulmonary and Metabolic Rehabilitation program at a cardiology reference center in Rio Grande do Sul, clinical evaluation was performed, as well as functional capacity by the 6-minute walk test, muscle strength and peripheral resistance by the sitting-rising test, and respiratory muscle strength by the manovacuometry exam. The values were below the predicted value. The proposed exercise program was performed during 30 sessions consisting of aerobic exercises lasting 33 minutes, added strength training of largemuscle groups. Conclusion: after the program there was an increase of 83 meters in the 6-minute walk test and an increase in respiratory muscle strength, as well as a reduction in Borg scale parameters.

Humans , Male , Adult , Pulmonary Arterial Hypertension , Exercise , Heart Defects, Congenital
Acta Physiologica Sinica ; (6): 646-656, 2021.
Article in Chinese | WPRIM | ID: wpr-887699


Pulmonary arterial hypertension (PAH) is a rare disease with a complex aetiology characterized by elevated pulmonary artery resistance, which leads to progressive right ventricular failure and ultimately death. The aberrant metabolism of arachidonic acid in the pulmonary vasculature plays a central role in the pathogenesis of PAH. The levels of 15-lipoxygenase (15-LO) and 15-hydroxyeicosatetraenoic acid (15-HETE) are elevated in the pulmonary arterial endothelial cells (PAECs), pulmonary smooth muscle cells (PASMCs) and fibroblasts of PAH patients. Under hypoxia condition, 15-LO/15-HETE induces pulmonary artery contraction, promotes the proliferation of PAECs and PASMCs, inhibits apoptosis of PASMCs, promotes fibrosis of pulmonary vessels, and then leads to the occurrence of PAH. Here, we review the research progress on the relationship between 15-LO/15-HETE and hypoxic PAH, in order to clarify the significance of 15-LO/15-HETE in hypoxic PAH.

Humans , Arachidonate 15-Lipoxygenase , Cell Proliferation , Cells, Cultured , Endothelial Cells , Hydroxyeicosatetraenoic Acids , Hypoxia , Myocytes, Smooth Muscle , Pulmonary Arterial Hypertension , Pulmonary Artery