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1.
Medicine (Baltimore) ; 98(42): e17615, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626139

RESUMO

BACKGROUND: The Fontan circulation is fragile, which is easily broken down. For now, there is no consensus on the drug treatment for the prevention of failure of the Fontan circulation. METHODS: Studies comparing pulmonary vasodilator and control in Fontan patients were identified by searching the PubMed, EMBASE, Clinical Trials, and the Cochrane Library databases until March 20, 2019. The assessed variables included the change of pulmonary resistance, heart function, exercise capacity, life of quality, mortality, and serials of adverse events before and after drug administration. A random-effect/fixed-effect model was used to summarize the estimates of the mean difference (MD)/risk ratio (RR) with 95% confidence interval (CI). Subgroup analysis stratified by drug was performed. RESULTS: This study will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will assess the efficacy and safety of pulmonary vasodilators for patients after Fontan procedure, and provide more evidence-based guidance in clinical practice. PROSPERO REGISTRATION NUMBER: CRD42019132135.


Assuntos
Técnica de Fontan/métodos , Cardiopatias Congênitas/cirurgia , Hipertensão Pulmonar/tratamento farmacológico , Circulação Pulmonar/efeitos dos fármacos , Pressão Propulsora Pulmonar/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Cardiopatias Congênitas/fisiopatologia , Humanos , Hipertensão Pulmonar/fisiopatologia
3.
Vet J ; 251: 105347, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31492386

RESUMO

Pulmonary hypertension (PH) is associated with substantial morbidity and if untreated, mortality. The human classification of PH is based on pathological, hemodynamic characteristics, and therapeutic approaches. Despite being a leading cause of PH, little is known about dogs with respiratory disease and/or hypoxia (RD/H)-associated PH. Therefore, our objectives were to retrospectively describe clinical features, diagnostic evaluations, final diagnoses and identify prognostic variables in dogs with RD/H and PH. In 47 dogs identified with RD/H and PH, chronic airway obstructive disorders, bronchiectasis, bronchiolar disease, emphysema, pulmonary fibrosis, neoplasia and other parenchymal disorders were identified using thoracic radiography, computed tomography, fluoroscopy, tracheobronchoscopy, bronchoalveolar lavage, and histopathology. PH was diagnosed using transthoracic echocardiography. Overall median survival was 276.0 days (SE, 95% CI; 216, 0-699 days). Dogs with an estimated systolic pulmonary arterial pressure (sPAP) ≥47mmHg (n=21; 9 days; 95% CI, 0-85 days) had significantly shorter survival times than those <47mmHg (n=16; P=0.001). Estimated sPAP at a cutoff of ≥47mmHg was a fair predictor of non-survival with sensitivity of 0.78 (95% CI, 0.52-0.94) and specificity of 0.63 (95% CI, 0.38-0.84). Phosphodiesterase-5 (PDE5) inhibitor administration was the sole independent predictor of survival in a multivariable analysis (hazard ratio: 4.0, P=0.02). Canine PH is present in a diverse spectrum of respiratory diseases, most commonly obstructive disorders. Similar to people, severity of PH is prognostic in dogs with RD/H and PDE5 inhibition could be a viable therapy to improve outcome.


Assuntos
Doenças do Cão/diagnóstico , Hipertensão Pulmonar/veterinária , Hipóxia/veterinária , Transtornos Respiratórios/veterinária , Animais , Doenças do Cão/tratamento farmacológico , Doenças do Cão/etiologia , Cães , Ecocardiografia/veterinária , Feminino , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Hipóxia/fisiopatologia , Masculino , Inibidores da Fosfodiesterase 5/uso terapêutico , Transtornos Respiratórios/fisiopatologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
4.
BMC Health Serv Res ; 19(1): 573, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412857

RESUMO

BACKGROUND: This study aims to assess the cost-effectiveness and budget impact of adopting sildenafil to the benefits package for the indication of pulmonary arterial hypertension (PAH), compared to beraprost. METHODS: Based on a societal perspective, a model-based economic evaluation was performed using local and international data to quantify the potential costs and health-related outcomes in terms of life years (LYs) and quality-adjusted life years (QALYs). RESULTS: The economic model calculated the incremental cost-effectiveness ratio (ICER) per QALY gained for using sildenafil as first-line therapy compared to beraprost for the patient in functional class (FC) II and III, i.e. USD 3098 and USD 2827, respectively. The results indicated that in spite of sildenafil being more expensive than beraprost, generic sildenafil could potentially be a good value for money since ICER per QALY is below one times gross domestic product (GDP) per capita in Indonesia. Furthermore, budget impact analysis estimated that the incremental budget needed within 5 years for including sildenafil compared to beraprost for PAH patients starting in FC II and FC III was USD 436,775 and USD 3.6 million, respectively. CONCLUSIONS: Compared to beraprost, sildenafil would be preferable for the treatment of PAH patients in FC II and FC III in Indonesia. The additional budget for adopting sildenafil compared to beraprost as the treatment of PAH in the benefits package was estimated at around USD 4.0 million.


Assuntos
Epoprostenol/análogos & derivados , Hipertensão Pulmonar/tratamento farmacológico , Citrato de Sildenafila/economia , Vasodilatadores/economia , Orçamentos , Análise Custo-Benefício , Epoprostenol/economia , Epoprostenol/uso terapêutico , Humanos , Hipertensão Pulmonar/economia , Indonésia , Citrato de Sildenafila/uso terapêutico , Vasodilatadores/uso terapêutico
5.
J Vet Cardiol ; 24: 7-19, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31405557

RESUMO

INTRODUCTION: Canine pulmonary hypertension (PH) is associated with high morbidity and mortality. Tadalafil, a phosphodiesterase-5 inhibitor used commonly in humans with PH, has not been evaluated in a clinical trial in dogs with naturally occurring PH. Our objectives were to compare the efficacy of tadalafil and sildenafil on PH assessed by peak tricuspid regurgitant flow velocity, estimated systolic pulmonary arterial pressure gradient, voluntary activity, quality of life, and safety profiles in dogs with moderate to severe PH. ANIMALS: Twenty-three dogs with echocardiographic evidence of moderate to severe PH were enrolled. METHODS: A prospective short-term, randomized, double-blinded pilot study was carried out. Dogs with PH were randomly allocated to receive sildenafil or tadalafil for 2 weeks and assessed via echocardiography, activity monitors, and owner-reported outcomes. RESULTS: Collectively, phosphodiesterase-5 inhibition significantly decreased (improved) quality of life scores (p = 0.003) and visual analog score (p = 0.024) without significant between-treatment difference of these variables. Phosphodiesterase-5 inhibition did not significantly affect peak tricuspid regurgitant flow velocity (p = 0.056) or voluntary activity (p = 0.27). A total of 33% (7/21) of dogs experienced at least one adverse event during the study (tadalafil, n = 5; sildenafil, n = 2) with no significant difference between treatment type and incidence of adverse events (p = 0.36). DISCUSSION: In this pilot study, phosphodiesterase-5 inhibition led to apparent improvement in quality of life scores without documenting superiority of tadalafil over sildenafil. CONCLUSION: Tadalafil at a dose of 2 mg/kg once daily appears to be a viable alternative to sildenafil in dogs with moderate to severe PH.


Assuntos
Doenças do Cão/tratamento farmacológico , Hipertensão Pulmonar/veterinária , Inibidores da Fosfodiesterase 5/uso terapêutico , Animais , Doenças do Cão/fisiopatologia , Cães , Método Duplo-Cego , Eletrocardiografia/veterinária , Feminino , Hipertensão Pulmonar/tratamento farmacológico , Masculino , Inibidores da Fosfodiesterase 5/administração & dosagem , Projetos Piloto , Estudos Prospectivos , Distribuição Aleatória , Índice de Gravidade de Doença , Citrato de Sildenafila/administração & dosagem , Citrato de Sildenafila/uso terapêutico , Inquéritos e Questionários , Tadalafila/administração & dosagem , Tadalafila/uso terapêutico , Resultado do Tratamento
6.
Complement Ther Med ; 45: 45-49, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31331581

RESUMO

BACKGROUND: Systematic and consistent dose delivery is critical in intervention research. Few studies testing complementary health approach (CHA) interventions describe intervention fidelity monitoring (IFM) and measurement. OBJECTIVE: To describe methodological processes in establishing and measuring consistent dose, delivery, and duration of a multi-component CHA intervention. METHODS: Adults with pulmonary hypertension received six weekly, 1-hour Urban Zen Integrative Therapy (UZIT) sessions. A total of 78 sessions were delivered and 33% of these sessions were audited. Intervention dose (time allocated to each component), intervention consistency (protocol adherence audits), and intervention delivery (performance and sequence of components) were captured using remote video observation and review of the recorded video. IFM audits were performed at the beginning (n = 16), middle (n = 5), and end (n = 5) of the study. RESULTS: UZIT interventionists adhered to the intervention protocol (99.3%) throughout the study period. Interventionists delivered UZIT components within the prescribed timeframe: 1) Beginning: gentle body movement (18.9 ± 5.8 min.), restorative pose with guided body awareness meditation (21.3 ± 2.7 min.), and Reiki (22.8 ± 3.1 min.); 2) Middle: gentle body movement (15.9 ± 1.5 min.), pose/body awareness meditation (30.1 ± 6.5 min.), and Reiki (30.1 ± 7.0 min.); 3) End: gentle body movement (18.1 ± 3.6 min.), pose/body awareness meditation (35.3 ± 6.4 min.), and Reiki (34.5 ± 7.0 min.). Essential oil inhalation was delivered during UZIT sessions 100% of the time. Interventionists adhered to treatment delivery behaviors throughout the study period: beginning (98.86%), middle (100%), and end (100%). DISCUSSION: In this pilot study, we demonstrated that the dose, consistency, and delivery of multi-component CHA therapy can be standardized and monitored to ensure intervention fidelity.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/terapia , Terapias Complementares/métodos , Assistência à Saúde/métodos , Feminino , Humanos , Masculino , Auditoria Médica/métodos , Terapias Mente-Corpo/métodos , Óleos Voláteis/administração & dosagem , Projetos Piloto
7.
Chem Biol Interact ; 311: 108749, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31325423

RESUMO

PURPOSE: Excessive proliferation, migration and anti-apoptosis of pulmonary artery smooth muscle cells (PASMCs) are the basis for the development of pulmonary vascular remodeling, and it is the driving force for pulmonary arterial hypertension (PAH). 18ß-glycyrrhetinic acid (18ß-GA) is the main active substance extracted from Chinese herbal medicine licorice, with outstanding anti-inflammatory, anti-oxidation and anti-proliferative effects. Our team found in previous studies that 18ß-GA has protective effects on monocrotaline-induced PAH in rats. However, the anti-angiogenic effect of 18ß-GA on PAH remains unclear. Therefore, in order to further investigate whether the beneficial effects of 18ß-GA on PAH are related to its antiproliferative effect, we conducted experiments in vivo and in vitro. METHODS AND RESULTS: In vivo, 18ß-GA relieved mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricular hypertrophy index, improving pulmonary remodeling. In vitro, 18ß-GA significantly inhibited PDGF-BB-induced proliferation and DNA synthesis of HPASMCs, blocking the progression of G0/G1 to S phase of the cell cycle. Furthermore, after treatment with 18ß-GA, the expression of Rho A, ROCK1, ROCK2 was decreased and ROCK activity was inhibited in HPASMC. In addition, 18ß-GA also attenuated PDGF-induced changes in p27kip1, Bax and Bcl-2. CONCLUSIONS: In summary, these results indicate that 18ß-GA regulates the activity of RhoA-ROCK signaling pathway, inhibits the proliferation of HPASMCs, and has potential value in the treatment of PAH.


Assuntos
Ácido Glicirretínico/análogos & derivados , Hipertensão Pulmonar/patologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glicirretínico/farmacologia , Ácido Glicirretínico/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Masculino , Monocrotalina/toxicidade , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Substâncias Protetoras/uso terapêutico , Proteína Fosfatase 1/genética , Proteína Fosfatase 1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Remodelação Vascular/efeitos dos fármacos , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/metabolismo
8.
Rev Med Chil ; 147(3): 281-288, 2019 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-31344164

RESUMO

BACKGROUND: Living above 2,500 meters in hypobaric conditions induces pulmonary arterial hypertension of the neonate (PAHN), a syndrome whose main features are: pathological remodeling of the pulmonary vessels, abnormal vascular reactivity and increased oxidative stress. Melatonin could have pulmonary antioxidant, anti-remodeling and vasodilating properties for this condition. AIM: To determine the effect of melatonin at the transcript level of prostanoid pathways in the lung of neonatal lambs gestated and born under hypobaric hypoxia. MATERIAL AND METHODS: Vehicle (1.4% of ethanol, n = 6) or melatonin (1 mg * kg1, n = 5) were administered from the postnatal day 4 to 21 to lambs gestated and born at 3,600 meters above sea level. After one week of treatment completion, lung tissue was obtained, the transcript and protein levels of prostanoid synthases and receptors were assessed by RT-PCR and Western Blot. RESULTS: Melatonin induced the expression of prostacyclin synthase transcript and increased protein expression of the prostacyclin receptor. In addition, the treatment decreased the expression of transcript and protein of cyclooxygenase-2, without changes in the expression of the prostanoid vasoconstrictor (thromboxane) pathway. CONCLUSIONS: Postnatal treatment with melatonin increases the expression of the prostacyclin-vasodilator pathway without changing the vasoconstrictor thromboxane pathway. Further, the decreased COX-2 induced by melatonin could be an index of lesser oxidative stress and inflammation in the lung.


Assuntos
Antioxidantes/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Melatonina/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Prostaglandinas/metabolismo , Animais , Animais Recém-Nascidos , Hipertensão Pulmonar/metabolismo , Hipóxia , Artéria Pulmonar/efeitos dos fármacos , Ovinos
9.
Congenit Heart Dis ; 14(4): 645-650, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31166081

RESUMO

OBJECTIVE: The optimal dose of Fasudil is still controversial in congenital heart disease accompanied with severe pulmonary hypertension (CHD-PAH). This study aimed to compare acute hemodynamic changes after different doses of Fasudil in 60 consecutive adult patients with CHD-PAH. DESIGN: Prospective randomized controlled trial. SETTING: Tertiary cardiology center. PATIENTS: Adult patients with CHD-PAH. INTERVENTIONS: Patients were randomized to Fasudil 30 or 60 mg. OUTCOME MEASURES: The hemodynamic parameters were measured at baseline and after 30 minutes of Fasudil through right cardiac catheterization. Blood gas results were obtained from the pulmonary artery, right ventricle, right atrium, superior and inferior vena cava, and femoral artery. Pulmonary vascular resistance (PVR) and systemic arterial resistance (SVR) were calculated. RESULTS: The changes in systolic pulmonary artery pressure (sPAP) (-13.1% vs -9.3%, P < .05), diastolic PAP (dPAP) (-17.6% vs -14.5%, P < .05), mean PAP (mPAP) (-12.4% vs -8.5%, P < .05), and PVR (-35.8% vs -22.2%, P < .05) were more pronounced in the 60-mg group than in the 30-mg group. All patients had no obvious adverse reactions related to peripheral blood pressure. CONCLUSIONS: Fasudil could improve the hemodynamics of patients with CHD-PAH, especially with the 60-mg dose. There were no serious adverse reactions.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Pressão Sanguínea/fisiologia , Cardiopatias Congênitas/tratamento farmacológico , Hipertensão Pulmonar/tratamento farmacológico , Resistência Vascular/efeitos dos fármacos , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/administração & dosagem , Adolescente , Adulto , Pressão Sanguínea/efeitos dos fármacos , Cateterismo Cardíaco , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/fisiopatologia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteínas Quinases/administração & dosagem , Resultado do Tratamento , Resistência Vascular/fisiologia , Adulto Jovem
10.
Lakartidningen ; 1162019 Mar 26.
Artigo em Sueco | MEDLINE | ID: mdl-31192396

RESUMO

Pulmonary hypertension is a common consequence of left heart disease, associated with poor prognosis. The pulmonary hypertension in left heart disease is initially caused by a passive congestion of the pulmonary circuit but may, if longstanding, result in endothelial dysfunction and excessive vasoconstriction. In some cases pulmonary vascular remodeling occur, further complicating the condition and worsening the prognosis. It has been debated whether these patients may benefit from pulmonary vasodilators presently used in pulmonary arterial hypertension. Several randomized controlled trials have been performed on this subject, the vast majority being negative. As maintenance therapy may be harmful, they should be avoided outside clinical trials.


Assuntos
Hipertensão Pulmonar , Vasodilatadores/efeitos adversos , Disfunção Ventricular Esquerda/complicações , Contraindicações de Medicamentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Vasodilatadores/uso terapêutico , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/fisiopatologia
12.
Respir Res ; 20(1): 123, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208454

RESUMO

BACKGROUND: Right ventricular (RV) angiogenesis has been associated with adaptive myocardial remodeling in pulmonary hypertension (PH), though molecular regulators are poorly defined. Endothelial cell VEGFR-2 is considered a "master regulator" of angiogenesis in other models, and the small molecule VEGF receptor tyrosine kinase inhibitor SU5416 is commonly used to generate PH in rodents. We hypothesized that SU5416, through direct effects on cardiac endothelial cell VEGFR-2, would attenuate RV angiogenesis in a murine model of PH. METHODS: C57 BL/6 mice were exposed to chronic hypoxia (CH-PH) to generate PH and stimulate RV angiogenesis. SU5416 (20 mg/kg) or vehicle were administered at the start of the CH exposure, and weekly thereafter. Angiogenesis was measured after one week of CH-PH using a combination of unbiased stereological measurements and flow cytometry-based quantification of myocardial endothelial cell proliferation. In complementary experiments, primary cardiac endothelial cells from C57 BL/6 mice were exposed to recombinant VEGF (50 ng/mL) or grown on Matrigel in the presence of SU5416 (5 µM) or vehicle. RESULT: SU5416 directly inhibited VEGF-mediated ERK phosphorylation, cell proliferation, and Kdr transcription, but not Matrigel tube formation in primary murine cardiac endothelial cells in vitro. SU5416 did not inhibit CH-PH induced RV angiogenesis, endothelial cell proliferation, or RV hypertrophy in vivo, despite significantly altering the expression profile of genes involved in angiogenesis. CONCLUSIONS: These findings demonstrate that SU5416 directly inhibited VEGF-induced proliferation of murine cardiac endothelial cells but does not attenuate CH-PH induced RV angiogenesis or myocardial remodeling in vivo.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Hipóxia/tratamento farmacológico , Indóis/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Pirróis/uso terapêutico , Inibidores da Angiogênese/farmacologia , Animais , Doença Crônica , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Hipertensão Pulmonar/patologia , Hipóxia/patologia , Indóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/patologia , Pirróis/farmacologia
13.
Med. infant ; 26(2): 168-176, Junio 2019. Tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-1016785

RESUMO

La hipertensión arterial pulmonar (HAP) en pediatría comparte características comunes de la enfermedad en adultos, pero está asociada con varios trastornos y desafíos adicionales que requieren enfoques diferentes. En este artículo se analizan los avances recientes, los desafíos actuales y los distintos enfoques para el cuidado de niños con HAP. Se actualizan la definición, epidemiología, clasificación, diagnóstico y tratamiento. Se plantea el uso del cateterismo cardíaco como diagnóstico y las definiciones hemodinámicas de HAP, incluido el test de vasorreactividad. Se proporcionan actualizaciones sobre los enfoques pediátricos específicos del manejo médico e intervencionista de la HAP (incluyendo la derivación de Potts). Aunque la falta de datos de ensayos clínicos para el uso de la terapia dirigida a la HAP, los datos emergentes están mejorando la identificación de objetivos adecuados para la terapia orientada a objetivos en niños.(AU)


Pulmonary arterial hypertension (PAH) in children shares the typical features of the disease in adults, but is associated with different disorders and additional challenges that require different approaches. This article discusses recent developments, current challenges, and different approaches to PAH care in children. Definition, epidemiology, classification, diagnosis, and treatment are updated. The use of cardiac catheterization as a diagnostic tool and hemodynamic definitions of PAH are proposed, including the vasoreactivity test. Updates are provided on specific pediatric approaches to the medical and interventional management of PAH (including Potts shunt). In spite of the lack of clinical trial data for the use of PAH-targeted therapy, emerging data are improving the identification of appropriate targets for therapy in children (AU)


Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Hipertensão Pulmonar/classificação , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/terapia , Hipertensão Pulmonar/epidemiologia , Cateterismo Cardíaco
14.
Med. infant ; 26(2): 177-188, Junio 2019. Tab
Artigo em Espanhol | LILACS | ID: biblio-1021533

RESUMO

El rotular a un niño o adolescente de hipertenso no es una tarea fácil en la actualidad. Sabemos que el pilar para el diagnóstico de Hipertensión Arterial sigue siendo la presión arterial de consultorio; pero tenemos que tener en cuenta que, por su escasa reproducibilidad éste método tiene limitaciones. Hoy existen métodos complementarios reproducibles, validados y confiables como el Monitoreo Ambulatorio de la Presión Arterial (MAPA) y el Monitoreo Domiciliario de la Presión Arterial (MDPA) menos difundido en pediatría, que nos ayudan a llegar a un diagnostico correcto (AU)


Diagnosis of a hypertensive child or adolescent is not an easy task today. We know that the mainstay for diagnosing arterial hypertension remains the measuring of blood pressure at the office; however, it is necessary to bear in mind that, because of its low reproducibility, this method has limitations. Today there are reproducible, validated, and reliable complementary methods, such as ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM), that are less widespread in pediatrics, which may be helpful to make an adequate diagnosis.(AU)


Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Argentina/epidemiologia , Monitorização Ambulatorial da Pressão Arterial/instrumentação , Hipertensão/diagnóstico , Hipertensão Pulmonar/tratamento farmacológico
15.
Clin Respir J ; 13(7): 467-479, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059198

RESUMO

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) results in a progressively worsening course associated with substantial morbidity and mortality. The purpose of this comprehensive study was to determine the clinical efficacy of targeted therapeutic interventions for this disease. METHODS: We searched Medline, Embase, Cochrane databases and Pubmed for relevant clinical studies. Randomized controlled trials comparing the effects of targeted treatments to control in CTEPH population were included. Pooled estimates were calculated using a random effect model. Heterogeneity was determined using the I2 statistic. RESULTS: This analysis included 6 studies with a total of 565 patients. We found that targeted treatments approved for pulmonary arterial hypertension (PAH) were associated with a larger improvement in exercise capacity, haemodynamic parameters, functional status and clinical symptom. There were no statistically significant differences associated with targeted treatments compared with control in all-cause mortality and safety outcomes. CONCLUSIONS: This is the first systematic review and meta-analysis of randomized controlled trials revealing a positive role of PAH-targeted therapies in CTEPH. Future larger randomized trials with a focus on long-term clinical outcomes are urgently needed.


Assuntos
Anti-Hipertensivos/uso terapêutico , Causas de Morte , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/mortalidade , Sistemas de Liberação de Medicamentos , Tolerância ao Exercício , Feminino , Hemodinâmica/fisiologia , Humanos , Hipertensão Pulmonar/diagnóstico , Masculino , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Análise de Sobrevida
16.
Cardiol Young ; 29(5): 589-593, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31046848

RESUMO

BACKGROUND: Enteral sildenafil may be used in the intensive care unit for treatment of pulmonary arterial hypertension. We aimed to determine if initial enteral sildenafil dosing is safe in children receiving concurrent vasoactive infusions. METHODS: We performed a single-centre retrospective chart review that included patients less than 2 years of age in paediatric and cardiovascular intensive care units at an academic medical centre from 1 January, 2010 to 30 November, 2016. Included patients received concomitant enteral sildenafil and a continuously infused vasoactive agent. Exclusion criteria consisted of mechanical circulatory support, any form of dialysis, or a suspicion of septic shock at the time of sildenafil initiation. We sought to identify patients who developed worsening hemodynamic instability after initiation of enteral sildenafil defined as one or more of the following observations within 24 hours of sildenafil initiation: sildenafil discontinuation, total fluid bolus receipt >10 ml/kg, increased vasoactive support, epinephrine intravenous push administration, and/or the initiation of mechanical circulatory support. RESULTS: Worsening hemodynamic instability was identified in 35% of the 130-patient cohort. Patients younger than 4 months were at increased risk of further hemodynamic instability compared with older patients (56% versus 44%, p = 0.0003) despite receiving lower median doses (1.28 mg/kg/day versus 1.78 mg/kg/day, p = 0.01). CONCLUSIONS: Critically ill children receiving vasoactive infusions may be at increased risk for further hemodynamic instability after initiation of enteral sildenafil, particularly in younger patients. This population may benefit from lower starting enteral sildenafil doses of 0.25 mg/kg/dose or less every 8 hours to avoid further hemodynamic compromise.


Assuntos
Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Citrato de Sildenafila/efeitos adversos , Vasodilatadores/efeitos adversos , Feminino , Humanos , Lactente , Infusões Intravenosas , Unidades de Terapia Intensiva , Masculino , Estudos Retrospectivos , Citrato de Sildenafila/administração & dosagem , Vasodilatadores/administração & dosagem
17.
Cochrane Database Syst Rev ; 5: CD012785, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042010

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterised by pulmonary vascular changes, leads to elevated pulmonary artery pressures, dyspnoea, a reduction in exercise tolerance, right heart failure, and ultimately death.Prostacyclin analogue drugs mimic endogenous prostacyclin which leads to vasodilation, inhibition of platelet aggregation, and reversal of vascular remodelling. Prostacyclin's short half-life theoretically enhances selectivity for the pulmonary vascular bed by direct (via central venous catheter) administration. Initial continuous infusion prostacyclins were efficacious, but use of intravenous access increases the risk of adverse events. Newer and safer subcutaneous, oral and inhaled preparations are now available, though possibly less potent.Selexipag is an oral selective prostacyclin receptor (IP receptor) agonist that works similarly to prostacyclin, potentially more stable, with less complex administration and titration. OBJECTIVES: To determine the efficacy and safety of prostacyclin, prostacyclin analogues or prostacyclin receptor agonists for PAH in adults and children. SEARCH METHODS: We performed searches on CENTRAL, MEDLINE, and Embase up to 16 September 2018. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. SELECTION CRITERIA: We included any randomised controlled trials (RCTs) which compared prostacyclin, prostacyclin analogues or prostacyclin receptor agonists to control (placebo, any other treatment or usual care) for at least six weeks. DATA COLLECTION AND ANALYSIS: We used standard methods specified by Cochrane. Primary outcomes included change in World Health Organization (WHO) functional class, six-minute walk distance (6MWD), and mortality. MAIN RESULTS: Seventeen trials with 3765 mostly adult participants were included; median trial duration was 12 weeks. Fifteen trials used prostacyclin analogues: intravenous (N = 4); subcutaneous (N = 1); oral (N = 5); inhaled (N = 5); two used oral prostacyclin receptor agonists. Three intravenous and two inhaled trials were open-label.Participants using prostacyclin had 2.39 times greater odds of improving by at least one WHO functional class (95% confidence interval (CI) 1.72 to 3.32; 24 per 100 (95% CI 18.5 to 30.4) with prostacyclin compared to 12 per 100 with control; 8 trials, 1066 participants; moderate-certainty evidence). Improvement occurred with intravenous (odds ratio (OR) 14.96, 95% CI 4.76 to 47.04), and inhaled (OR 2.94, 95% CI 1.53 to 5.66), but not with oral preparations. Participants using prostacyclin increased their 6MWD by 19.50 metres (95% CI 14.82 to 24.19; 13 trials, 2283 participants; low-certainty evidence), which was clinically significant with intravenous (mean difference (MD) 91.76 metres; 95% CI 58.97 to 124.55), but not with non-intravenous preparations (subcutaneous: MD 16.00 metres, 95% CI 7.38 to 24.62; oral: MD 14.76 metres, 95% CI 7.81 to 21.70; inhaled: MD 26.97 metres, 95% CI 17.21 to 36.73). Mortality was reduced in the intravenous (OR 0.29, 95% CI 0.12 to 0.69; risk of death 6 per 100 (95% CI 2.38 to 12.31) with prostacyclin compared to 17 per 100 with control; 4 trials, 255 participants), but not in the non-intravenous studies (OR 0.82, 95% CI 0.48 to 1.40; risk of death 21 per 1000 (95% CI 12.00 to 34.20) with prostacyclin compared to 25 per 1000 with control; moderate-certainty evidence; 12 trials, 2299 participants). We reduced the certainty of evidence due to few studies per subgroup and use of open-label trials.Prostacyclins improved cardiopulmonary haemodynamics (reduction in mean pulmonary artery pressure by 3.60 mmHg (95% CI -4.73 to -2.48); pulmonary vascular resistance by 2.81 WU (95% CI -3.80 to -1.82); right atrial pressure by 1.90 mmHg (95% CI -2.58 to -1.22), and increase in cardiac index by 0.31 L/min/m2 (95% CI 0.23 to 0.38); low-certainty evidence), improved dyspnoea (low-certainty evidence, and improved quality of life (moderate-certainty evidence), when compared to control. When only subcutaneous/inhaled trials were included the effect was still significant, but the magnitude was smaller. There was no difference across oral trials.Adverse events were increased in all prostacyclin preparations, including vasodilation (OR 5.03, 95% CI 3.84 to 6.58), headache (OR 3.16, 95% CI 2.62 to 3.80), jaw pain (OR 5.25, 95% CI 3.96 to 6.98), diarrhoea (OR 2.81, 95% CI 2.29 to 3.46), nausea/vomiting (OR 2.39, 95% CI 1.98 to 2.88), myalgias (OR 2.75, 95% CI 1.65 to 4.58), upper respiratory tract events (OR 1.61, 95% CI 1.22 to 2.13), extremity pain (OR 3.36, 95% CI 2.32 to 4.85), and infusion site reactions (OR 14.41, 95% CI 9.16 to 22.66). In the intravenous trials, there was a 12%-25% risk of serious non-fatal events including sepsis, haemorrhage, pneumothorax and pulmonary embolism.Two trials (1199 participants) compared oral selexipag to placebo; no trials compared selexipag with prostacyclin. There was a small 12.62 metre improvement in 6MWD (95% CI 1.90 to 23.34; high-certainty evidence), and weak evidence for haemodynamics. The effect was uncertain for WHO functional class. The risk of death with selexipag was five per 100 compared to three per 100 with placebo, though the CI crossed zero so the true effect is uncertain (risk difference (RD) 0.02 (95% CI -0.00 to 0.04). There was less clinical worsening with selexipag (OR 0.47, 95% CI 0.37 to 0.60), though more side effects, including vasodilation (OR 2.67, 95% CI 1.72 to 4.17), headache (OR 3.91, 95% CI 3.07 to 4.98), jaw pain (OR 5.33, 95% CI 3.64 to 7.81), diarrhoea (OR 3.11, 95% CI 2.39 to 4.05), nausea/vomiting (OR 2.92, 95% CI 2.29 to 3.73), pain in the extremities (OR 2.44, 95% CI 1.69 to 3.52), and myalgias (OR 3.05, 95% CI 2.02 to 4.58). AUTHORS' CONCLUSIONS: This review demonstrates clinical and statistical benefit for intravenous prostacyclin (compared to control) with improved functional class, 6MWD, mortality, symptoms scores, and cardiopulmonary haemodynamics, but at a cost of adverse events. This may be due to a true effect, or may be overestimated due to the inclusion of small, short or open-label studies. There was a statistical and small clinical benefit in function and haemodynamics for inhaled prostacyclin, but the effect is uncertain for mortality. The effect of oral prostacyclins are less certain. Selexipag demonstrated less clinical worsening without discernable impact on survival, increased adverse events; and the effect on other outcomes is less certain. Real-world registry data may provide further information about clinical effect.


Assuntos
Anti-Hipertensivos/uso terapêutico , Epoprostenol/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Dispneia/tratamento farmacológico , Tolerância ao Exercício , Humanos , Qualidade de Vida
18.
Biomed Pharmacother ; 115: 108933, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31060005

RESUMO

Long non-coding RNA (lncRNA) plays important roles in many diseases, including pulmonary hypertension. The anti-diabetic drug metformin has been discovered to have protective effect on experimental pulmonary artery hypertension (PAH). However, the exact mechanism of metformin on the expression of lncRNA in PAH remains unclear. Here, we applied microarray analysis to examine lncRNA and mRNA expression proflies in pulmonary arteries (PAs) tissues of PAH rats with or without metformin treatment. A total of 24 lncRNAs (14 upregulated and 10 down-regulated) and 82 mRNAs (17 upregulated and 65 down-regulated) were differently expressed in PAH rats induced by MCT, whereas 83 lncRNAs (59 upregulated and 24 down-regulated) and 145 mRNAs (110 upregulated and 35 down-regulated) were differently expressed after metformin treatment. The expression levels of lncRNAs (NONRATT015587.2, NONRATT006975.2, NONRATT031226.2 and NONRATT024291.2 et al) were verified through realtime-PCR, and the results of NONRATT015587.2 and NONRATT024291.2 were consistent with RNA sequencing. Bioinformatics analysis was performed, including gene ontology (GO) analysis and genomes (KEGG) analysis. Transcription factor (TF)-target network analysis revealed that metformin regulated gene expression potentially via TFs including Tp53, Est1, Sp1 and Hif1α. The analysis illustrated that overexpression of NONRATT015587.2 promoted proliferation and knockdown of NONRATT015587.2 increased apoptosis of pulmonary artery smooth muscle cells in vitro, both of which were implicated in vascular remodeling in PAH. In addition, we found that the p53 and Hif1α signaling pathways may be involved in this regulation process. NONRATT015587.2 can be expected as a novel candidate in diagnostic markers for PAH. Our results provide novel insight into the mechanisms of the pivotal lncRNA-mRNA interactions, and indicate that NONRATT015587.2 acts as a pro-proliferative factor in regulation of pulmonary vascular remodeling.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Metformina/uso terapêutico , Monocrotalina , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Remodelação Vascular/efeitos dos fármacos , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Regulação da Expressão Gênica , Ontologia Genética , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/patologia , Análise em Microsséries , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Ratos Wistar , Remodelação Vascular/genética
19.
Transplant Proc ; 51(5): 1435-1438, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31079941

RESUMO

Portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis. Patients with severe PPHTN are contraindicated for liver transplant because of the associated risk of intraoperative acute right heart failure during reperfusion phase or massive volume infusion. Therefore, it has been recommended that patients with moderate to severe PPHTN undergo medical treatment to lower the pulmonary artery pressure before undergoing transplant. Herein, we report 3 patients with severe PPHTN who underwent sildenafil monotherapy before living donor liver transplant. None of the patients experienced associated adverse effects during sildenafil treatment, and the pulmonary artery pressure was effectively reduced before transplant. The first patient was diagnosed during anesthesia prior to transplant, and the mean pulmonary artery pressure was reduced by 34% after treatment. The second and third patients were followed-up with echography, and the estimated pulmonary artery systolic pressure were reduced by 34% and 47%, respectively. Pretransplant right heart catheterization also confirmed the reduction of the mean pulmonary artery pressure. Intraoperative hemodynamic parameters were stable, and the 3 patients were discharged uneventfully. After transplant, sildenafil was discontinued, and all patients remained in a stable clinical and functional status during follow-up.


Assuntos
Hipertensão Portal/tratamento farmacológico , Hipertensão Pulmonar/tratamento farmacológico , Transplante de Fígado/métodos , Citrato de Sildenafila/uso terapêutico , Vasodilatadores/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Feminino , Humanos , Hipertensão Portal/etiologia , Hipertensão Pulmonar/etiologia , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade
20.
Eur J Pharmacol ; 855: 227-234, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31085236

RESUMO

Phosphatase and tensin homolog (PTEN) plays an important role in the pathogenesis of hypoxic pulmonary hypertension (HPH). A decrease in PTEN expression is associated with the hypermethylation of its promoter. However, whether the demethylation of the PTEN gene could attenuate HPH remains unknown. 5-Aza-2'-deoxycytidine (5-Aza-dC) is a DNA methyltransferase (DNMT) inhibitor. The present study was designed to investigate the effects and mechanisms of 5-Aza-dC on HPH. The proliferation, migration and apoptosis of rat pulmonary artery smooth muscle cells (PASMCs) induced by hypoxia and treated with 5-Aza-dC were detected. The expression of PTEN and DNMTs and the PTEN methylation status of PASMCs were detected. SD rats were randomly divided into normal group, hypoxia group and hypoxia + 5-Aza-dC group. The expression of PTEN was decreased, the expression of DNMTs was increased, and the methylation status of PTEN was increased in hypoxia-induced PASMCs. However, 5-Aza-dC can rescue the decreased PTEN, inhibit DNMT levels in a dose-dependent manner and suppress PTEN methylation. Furthermore, the demethylation of PTEN, which was induced by 5-Aza-dC, inhibited the proliferation, migration and promoted apoptosis in PASMCs. In vivo studies further demonstrated that the expression of PTEN, mean pulmonary artery pressure and right ventricular hypertrophy index in HPH rats was attenuated by 5-Aza-dC. 5-Aza-dC also suppressed the expression of DNMTs and PTEN methylation in the lungs of HPH rats. These results indicated that PTEN promoter methylation status is involved in HPH. 5-Aza-dC, as a DNMT inhibitor, has the potential to attenuate HPH via demethylation of the PTEN promoter.


Assuntos
Metilação de DNA/efeitos dos fármacos , Decitabina/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/genética , PTEN Fosfo-Hidrolase/genética , Regiões Promotoras Genéticas/genética , Animais , Apoptose/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Decitabina/uso terapêutico , Hipertensão Pulmonar/patologia , Masculino , Ratos , Ratos Sprague-Dawley
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