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1.
Kardiologiia ; 60(7): 28-35, 2020 Aug 11.
Artigo em Russo | MEDLINE | ID: mdl-33155938

RESUMO

Aim To compare results of 24-h treatments with bosentan and macitentan by the clinical functional status and indexes of pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH).Materials and methods Based on the Russian National Registry (NCT03707561), 44 patients older than 18 years with PAH (34 patients with idiopathic pulmonary hypertension (IPH) and 10 patients with Eisenmenger syndrome) were retrospectively included into this study. Based on the statistical method of pairwise comparison, two groups were formed and matched by age, gender, WHO functional class (FC), and 6-min walk distance (6MWD). 22 patients of group 1 (17 with IPH and 5 with Eisenmenger syndrome) were treated with macitentan 10 mg/day, and 22 patients of group 2 (17 with IPH and 5 with Eisenmenger syndrome) were treated with bosentan 250 mg/day. Clinical instrumental data (6MWD, Borg dyspnea score, chest X-ray, transthoracic echocardiography (EchoCG), and right heart catheterization (RHC)) were evaluated at baseline and after 24 weeks of therapy.Results By week 24 of the treatment, FC and 6MWD improved in both groups. The macitentan treatment was associated with a significant decrease in Borg score. Significant intergroup differences in EchoCG data were not observed. The bosentan treatment was associated with a decrease in right ventricular (RV) dimension and a tendency towards a decrease in calculated pulmonary artery systolic pressure (PASP). By week 24, the macitentan treatment as compared to the bosentan treatment, was associated with a decrease in cardiothoracic ratio (CTR). In both groups, RHC showed decreases in PASP, mean pulmonary artery pressure and pulmonary vascular resistance, and improvements in cardiac output (CO), cardiac index, and stroke volume (SV) values. By week 24, the increase in SV was greater in the macitentan treatment group than in the bosentan treatment group (р=0.05).Conclusion The 24-week treatment with bosentan or macitentan provided significant and comparable improvement of the functional profile in PAH patients with FC II (WHO) at baseline. The decrease in CTR was significantly more pronounced in the macitental treatment group compared to the bosentan treatment group. The 24-week bosentan treatment resulted in a decrease in RV anterior-posterior dimension, a tendency towards a decrease in PASP according to EchoCG data. Macitentan provided more pronounced dynamics of dyspnea than bosentan according to the results of 6MWD test and the increase in SV according to RHC data.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Anti-Hipertensivos/uso terapêutico , Bosentana , Antagonistas dos Receptores de Endotelina/farmacologia , Hipertensão Pulmonar Primária Familiar/tratamento farmacológico , Hemodinâmica , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Pirimidinas , Estudos Retrospectivos , Federação Russa , Sulfonamidas , Resultado do Tratamento
2.
Kardiologiia ; 60(8): 115-123, 2020 Sep 17.
Artigo em Russo | MEDLINE | ID: mdl-33155967

RESUMO

Chronic thromboembolic pulmonary hypertension (CTEPH) is a precapillary type of pulmonary hypertension with chronic obstruction of large and medium branches of pulmonary arteries along with secondary alterations in pulmonary microcirculation, which cause progressive increases in pulmonary vascular resistance and pulmonary arterial pressure and ensuing severe right heart dysfunction and heart failure. Pulmonary thromboendarterectomy (PTE) is the treatment of choice for CTEPH; however, this procedure is available not for all patients. Although the surgery performed in the conditions of centers with advanced experience generally shows good results, up to 40% of patients are technically inoperable or PTE is associated with a high risk of complications. At present, riociguat, the only officially approved drug from the class of soluble guanylate cyclase stimulators, is considered as a first-line treatment for inoperable and residual forms of STEPH. Introduction of riociguat to clinical practice can be called a real breakthrough in the treatment of patients with STEPH who cannot undergo PTE or those with relapse or persistent STEPH after the surgery.


Assuntos
Hipertensão Pulmonar , Embolia Pulmonar , Doença Crônica , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Embolia Pulmonar/complicações , Embolia Pulmonar/tratamento farmacológico , Pirazóis , Pirimidinas , Guanilil Ciclase Solúvel
3.
Sheng Li Xue Bao ; 72(5): 541-550, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33106824

RESUMO

The occurrence and development of pulmonary arterial hypertension (PAH) is closely related to the genetic mutation of bone morphogenetic protein receptor type II (BMPRII) encoding gene and the inflammatory response mediated by nuclear factor κB (NF-κB) pathway. This paper was aimed to investigate the effect of NF-κB pathway inhibitors on lipopolysaccharide (LPS)-induced pulmonary artery endothelial cell injury. Human pulmonary artery endothelial cells were treated with 1 µg/mL of LPS. The expression levels of BMPRII and interleukin-8 (IL-8) were detected by Western blot and qPCR. The rat PAH model was established by intraperitoneal (i.p.) injection of monocrotaline (MCT). The expression levels of BMPRII and IL-8 in pulmonary artery endothelial cells were detected by immunofluorescence staining. Cardiac hemodynamic changes and pulmonary vascular remodeling were detected in the MCT-PAH model rats. The results showed that LPS caused down-regulation of BMPRII expression and up-regulation of IL-8 expression in human pulmonary artery endothelial cells. NF-κB inhibitor BAY11-7082 (10 µmol/L) reversed the effect of LPS. In the pulmonary artery endothelial cells of MCT-PAH model, BMPRII expression was down-regulated, IL-8 expression was up-regulated, weight ratio of right ventricle to left ventricle plus septum [RV/(LV+S)] and right ventricular systolic pressure (RVSP) were significantly increased, cardiac output (CO) and tricuspid annular plane systolic excursion (TAPSE) were significantly reduced, and pulmonary vessel wall was significantly thickened. BAY11-7082 (5 mg/kg, i.p., 21 consecutive days) reversed the above changes in the MCT-PAH model rats. These results suggest that LPS down-regulates the expression level of BMPRII through NF-κB signaling pathway, promoting the occurrence and development of PAH. Therefore, the NF-κB pathway can be used as a potential therapeutic target for PAH.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II , Hipertensão Pulmonar , Animais , Regulação para Baixo , Células Endoteliais/metabolismo , Humanos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Lipopolissacarídeos , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Remodelação Vascular
4.
Artigo em Inglês | MEDLINE | ID: mdl-33093771

RESUMO

Background: Pulmonary hypertension (PH) is a known complication of pulmonary sarcoidosis and is associated with higher morbidity and mortality. Currently, there are no approved PH-targeted therapies for sarcoidosis-associated pulmonary hypertension (SAPH). Macitentan is frequently used as treatment for pulmonary arterial hypertension, but no results are known in the SAPH population. Objective: We investigated the safety and effect of macitentan as treatment for SAPH. Methods: We retrospectively reviewed our patient database for all SAPH patients receiving macitentan as treatment, with a minimum follow-up of twelve months for monitoring safety. Safety outcomes included reported side-effects, hospitalisations and mortality. Furthermore, six-minutes walking distance, New York Heart Association functional class and NT-proBNP levels were collected. Results: Six cases (three men) with a median age of 64 years (range 52-74 years) were identified. During macitentan treatment, one patient experienced side effects and aborted therapy after five days of treatment and died 16 months later. Three patients were hospitalised during treatment for congestive heart failure. Four patients showed improvement of their functional class and three patients in exercise capacity after 12 months of therapy. Conclusion: Macitentan was well tolerated in five out of six cases with severe pulmonary sarcoidosis and PH. Functional capacity improved in four cases. Prospective controlled trials are warranted before therapeutic recommendations can be made. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 74-78).


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Antagonistas dos Receptores de Endotelina/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Pirimidinas/uso terapêutico , Sarcoidose Pulmonar/complicações , Sulfonamidas/uso terapêutico , Idoso , Anti-Hipertensivos/efeitos adversos , Bases de Dados Factuais , Antagonistas dos Receptores de Endotelina/efeitos adversos , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Sarcoidose Pulmonar/diagnóstico , Fatores de Tempo , Resultado do Tratamento
5.
Sarcoidosis Vasc Diffuse Lung Dis ; 37(2): 184-191, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33093782

RESUMO

Sarcoidosis-Associated Pulmonary Hypertension (SAPH) is a common finding in patients with chronic sarcoidosis and is associated with increased mortality. The optimal treatment for SAPH is not known; however, therapies approved for Group 1 pulmonary hypertension have improved hemodynamics and functional status. Prostanoids, including epoprostenol, have been therapeutic in short-term studies of SAPH, but long-term efficacy is unknown. In this study, we evaluated the long-term effect of epoprostenol therapy in 12 patients with SAPH. Hemodynamic assessment after an average of 4.1 years of epoprostenol therapy demonstrated significant improvement in mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output; furthermore, patients demonstrated improved NYHA functional class. To evaluate further the long-term effect of epoprostenol, we compared survival of SAPH patients to a cohort of hemodynamically matched patients from the same center treated with epoprostenol for Idiopathic Pulmonary Arterial Hypertension (IPAH). Interestingly, there was no difference in survival, despite the additional systemic disease burden of the SAPH subjects. Subgroup analysis by Scadding stage demonstrated that Scadding stages 1-3 had improved survival compared to Scadding stage 4. These observations suggest that epoprostenol is an effective long-term therapy for patients with SAPH; it improves hemodynamics, functional class, and provides survival similar to that seen in a hemodynamically-matched cohort of IPAH patients. Furthermore, we identify a subgroup of SAPH patients (nonfibrotic lung disease Scadding 1-3) who may derive significant benefit from prostanoid therapy. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 184-191).


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Epoprostenol/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Sarcoidose/complicações , Adulto , Anti-Hipertensivos/efeitos adversos , Débito Cardíaco/efeitos dos fármacos , Doença Crônica , Epoprostenol/efeitos adversos , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Estudos Retrospectivos , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Resistência Vascular/efeitos dos fármacos
6.
Sarcoidosis Vasc Diffuse Lung Dis ; 37(2): 234-238, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33093789

RESUMO

Sarcoid Associated Pulmonary Hypertension (SAPH) is a common complication of sarcoidosis and is associated with poor prognosis. SAPH can be due to multiple synergistic mechanisms and current therapeutic strategies treat systemic sarcoidosis and pulmonary hypertension separately. Several studies have been performed to develop an effective therapy for SAPH but have been met with mixed results. The AMBITION trial successfully treated incident patients with pulmonary arterial hypertension (PAH) with the upfront combination of ambrisentan and tadalafil; however combination therapy has not yet been studied in patients with SAPH. Here we report a cohort of patients with newly diagnosed SAPH who were treated with upfront combination therapy per the AMBITION study protocol. We report three subjects with newly diagnosed SAPH who were treated with combination ambrisentan and tadalafil. Baseline hemodynamics were compared with those from surveillance right heart catheterization while on therapy. Mean follow up period was 17 months. Each subject demonstrated clinical and hemodynamic improvement with combination therapy. This series is the first to evaluate upfront combination ambrisentan and tadalafil therapy for treatment of newly diagnosed SAPH. Despite the impressive clinical and hemodynamic improvement, the study is limited by its small size and retrospective nature. While these initial results are promising, further work is needed to fully evaluate this regimen for treatment of SAPH. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 234-238).


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Antagonistas do Receptor de Endotelina A/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Fenilpropionatos/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Artéria Pulmonar/efeitos dos fármacos , Piridazinas/uso terapêutico , Sarcoidose Pulmonar/complicações , Tadalafila/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Estudos Retrospectivos , Sarcoidose Pulmonar/diagnóstico , Resultado do Tratamento
7.
J Pharmacol Sci ; 144(4): 237-244, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33070843

RESUMO

Hypoxic pulmonary hypertension (HPH) is a progressive and irreversible disease that reduces survival. Echinacoside is a phenylethanoid glycoside from Tibetan herbs known for its vasorelaxant effect and for inhibiting the proliferation of rat pulmonary arterial smooth muscle cells. This study aimed to investigate the effect of echinacoside on HPH. Sprague Dawley rats were housed in a hypobaric hypoxia chamber (4500 m) for 28 days to obtain the HPH model. Echinacoside (3.75, 7.5, 15, 30 and 40 mg/kg) was administered by intraperitoneal injection from the 1st to the 28th day. The mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index, hemoglobin, hematocrit, red blood cell concentration and morphological change of pulmonary arteries were evaluated. Vascular perfusion assay was used to assess the pulmonary artery function. Echinacoside reduced mPAP, hemoglobin, hematocrit, right ventricular hypertrophy index and mean wall thickness% of pulmonary arteries in HPH rats. It significantly increased maximum vasoconstriction percentage of pulmonary arteries induced by noradrenaline in a dose-dependent manner. In addition, it improved the responsiveness of pulmonary arteries to acetylcholine and sodium nitroprusside. Therefore, Echinacoside might be an effective treatment against HPH, since it regulated pulmonary artery endothelium and smooth muscle layer function and improved the remodeling of pulmonary artery.


Assuntos
Glicosídeos/administração & dosagem , Glicosídeos/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Fitoterapia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Remodelação Vascular/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glicosídeos/uso terapêutico , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/prevenção & controle , Técnicas In Vitro , Injeções Intraperitoneais , Masculino , Ratos Sprague-Dawley , Vasodilatadores
9.
Int Heart J ; 61(5): 1084-1087, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921661

RESUMO

Diazoxide, a drug used to treat hyperinsulinemic hypoglycemia (HH), is associated with pulmonary hypertension (PH), as reported by the US Food and Drug Administration. However, no report has detailed the association between diazoxide dose and PH development. We report a case of an infant with HH, subsequently complicated by diazoxide-induced PH. When diazoxide was introduced, PH did not appear initially, but it developed during increased dosing. We monitored PH via regular echocardiography examinations. PH gradually improved with tapering of the diazoxide dose and disappeared after drug discontinuation. Our case suggests a diazoxide dose threshold might induce PH. Therefore, close echocardiography examinations should accompany diazoxide treatment.


Assuntos
Síndrome de Beckwith-Wiedemann/diagnóstico , Hiperinsulinismo Congênito/tratamento farmacológico , Diazóxido/efeitos adversos , Hipertensão Pulmonar/induzido quimicamente , Fator Natriurético Atrial/sangue , Síndrome de Beckwith-Wiedemann/complicações , Cateterismo Cardíaco , Hiperinsulinismo Congênito/etiologia , Desprescrições , Diazóxido/administração & dosagem , Diuréticos/uso terapêutico , Relação Dose-Resposta a Droga , Ecocardiografia , Eletrocardiografia , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/tratamento farmacológico , Lactente , Recém-Nascido , Masculino , Peptídeo Natriurético Encefálico/sangue , Citrato de Sildenafila/uso terapêutico , Vasodilatadores/uso terapêutico
10.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32943536

RESUMO

OBJECTIVES: To evaluate the survival and neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants at 18 to 26 months with early hypoxemic respiratory failure (HRF). We also assessed whether African American infants with early HRF had improved outcomes after exposure to inhaled nitric oxide (iNO). METHODS: ELBW infants ≤1000 g and gestational age ≤26 weeks with maximal oxygen ≥60% on either day 1 or day 3 were labeled as "early HRF" and born between 2007 and 2015 in the Neonatal Research Network were included. Using a propensity score regression model, we analyzed outcomes and effects of exposure to iNO overall and separately by race. RESULTS: Among 7639 ELBW infants born ≤26 weeks, 22.7% had early HRF. Early HRF was associated with a mortality of 51.3%. The incidence of moderate-severe NDI among survivors was 41.2% at 18 to 26 months. Mortality among infants treated with iNO was 59.4%. Female sex (adjusted odds ratio [aOR]: 2.4, 95% confidence interval [CI]: 1.8-3.3), birth weight ≥720 g (aOR: 2.3, 95% CI: 1.7-3.1) and complete course of antenatal steroids (aOR: 1.6, 95% CI: 1.1-2.2) were associated with intact survival. African American infants had a similar incidence of early HRF (21.7% vs 23.3%) but lower exposure to iNO (16.4% vs 21.6%). Among infants with HRF exposed to iNO, intact survival (no death or NDI) was not significantly different between African American and other races (aOR: 1.5, 95% CI: 0.6-3.6). CONCLUSIONS: Early HRF in infants ≤26 weeks' gestation is associated with high mortality and NDI at 18 to 26 months. Use of iNO did not decrease mortality or NDI. Outcomes following iNO exposure were not different in African American infants.


Assuntos
Broncodilatadores/uso terapêutico , Hipóxia/complicações , Lactente Extremamente Prematuro , Transtornos do Neurodesenvolvimento/epidemiologia , Óxido Nítrico Sintase Tipo II/uso terapêutico , Insuficiência Respiratória/mortalidade , Administração por Inalação , Afro-Americanos , Índice de Apgar , Peso ao Nascer , Broncodilatadores/administração & dosagem , Feminino , Ruptura Prematura de Membranas Fetais , Mortalidade Hospitalar , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Incidência , Lactente , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Masculino , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Transtornos do Neurodesenvolvimento/etnologia , Óxido Nítrico Sintase Tipo II/administração & dosagem , Alta do Paciente , Gravidez , Pontuação de Propensão , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/etnologia , Insuficiência Respiratória/etiologia , Fatores de Risco , Fatores Sexuais , Esteroides/uso terapêutico
12.
AAPS PharmSciTech ; 21(6): 221, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32748291

RESUMO

Sildenafil citrate causes vasodilatation, relaxation of the smooth muscle, and reduction of pulmonary arterial pressure. The latter property makes sildenafil citrate efficient for the treatment of cardiovascular diseases, including pulmonary arterial hypertension. Pediatric patients with pulmonary arterial hypertension are more susceptible to errors in drug administration than adults because of a lack of suitable drug dosages. Thus, the purpose of this study was to develop stable (chemically and microbiologically) sildenafil citrate drop liquid formulation, suitable for pediatric patients (including diabetics), ensuring safety during preparation and storing and improving palatability by using milk as a carrier for administration. The significant factors that affect the sildenafil solubility were evaluated by applying a Plackett-Burman design using two levels with six variables. The experiment showed that the type of buffer and glycerin content influenced the sildenafil solubility. The developed formulations proved to be stable for 6 months at all three assayed conditions (40± 2°C, 75 ± 5% RH; 25± 2°C, 60 ± 5% RH; and 4 ± 2°C). The microbiological tests fit with the requirement of the pharmacopeia at day 0 and 90 and even more at day 180. Finally, the palatability assay showed that 0.82 mL of the formulation containing buffer phosphate, 20% glycerin, and 4 mg mL-1 of sildenafil citrate diluted in 4.8 mL milk (which fits the medium pediatric dose) presented similar palatability to milk alone, and no precipitate or turbidity was observed. Graphical abstract.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Citrato de Sildenafila/química , Adulto , Criança , Composição de Medicamentos , Estabilidade de Medicamentos , Humanos , Pessoa de Meia-Idade , Citrato de Sildenafila/uso terapêutico , Solubilidade , Soluções
13.
Mendoza; s.n; 5 ago. 2020.
Não convencional em Espanhol | BRISA/RedTESA | ID: biblio-1118694

RESUMO

CONTEXTO: La HAP es una condición crónica progresiva de baja incidencia, estimada en 2,4/1mill./año y una prevalencia de 15casos /mill.hab/año por lo que se la considera una enfermedad rara. Los síntomas más comunes son disnea, dolor torácico, fatiga y síncope. Presenta una elevada mortalidad y su sobrevida alcanza 2,8 años en adultos sin tratamiento. El objetivo terapéutico del abordaje de la enfermedad es mejorar la función pulmonar, alcanzando una clase funcional I, ya que las clases funcionales III y IV se asocian con un riesgo medio y elevado de muerte. Los datos de incidencia en Argentina provienen de un estudio realizado en base a datos del Censo 2001 y proyecciones en el que se identificó una tasa de mortalidad de 1.39 y 2.39 muertes/millón habitantes (promedio 76 muertes/año); con un predominio sexo femenino (1.76 a 3.16/millon) en comparación con los varones (0.9 a 2.11/millón). los tratamientos disponibles los mismos abarcan medidas terapéuticas generales, fármacos inespecíficos (diuréticos, anticoagulantes, oxigenoterapia y fármacos específicos como Bloqueantes de los canales del Ca, Antagonistas de los receptores de endotelina, Inhibidores de la Fosfodiesterasa-5(IP-5), Análogos de Prostaciclina. Selexipag (ATC: B01AC27), es un agonista del receptor IP de prostaciclina, activa la vía IP2, produciendo relajación de las Células del Músculo Liso Arterial Pulmonar. Se administra una dosis inicial de 200 mcg dos veces al día, hasta un máximo de 1600 mcg dos veces al día, en escalonamiento semanales. METOLODOGÍA: El objetivo del presente fue analizar la evidencia disponible sobre eficacia, seguridad de Selexipag en el tratamiento de Hipertensión Arterial Pulmonar (HAP)y emitir una recomendación de cobertura. Se realizó una búsqueda bibliográfica sistematizada, la que permitió hallar 33 documentos de los que se seleccionaron por criterio (completos, diseño) 17 para su análisis. Paralelamente se evaluó el impacto presupuestario para el Ministerio de Salud, y los impactos en la equidad y en la salud pública. La calidad de la evidencia disponible para la droga es moderada (ensayos clínicos vs placebo, no existen comparaciones directas, desenlaces combinados). La magnitud de los beneficios en el paciente tales como mejora en la Clase funcional, mortalidad y sobrevida es ESCASO ó nulos, según la evidencia analizada. Emitir una recomendación de cobertura para pacientes de la provincia de Mendoza. RESULTADOS: Se incluyeron 4 Ensayos clínicos, una Revisión sistemática y un metaanálisis en red. CONCLUSIONES: Escaso beneficio clínico de Selexipag en el tratamiento de la HAP I, Clase funcional II-III, (sección 9-f) junto a impactos negativos en demás aspectos valorados, no permiten recomendar la inclusión a la cobertura del Ministerio de Salud. Asegurar la continuidad de los tratamientos como ARE, Bloq.Calcio, IP-5 como el resto de las medidas de apoyo a los pacientes para evitar la progresión de la enfermedad, resulta clave. Se establece revisar la evidencia para la droga en el término de un año, ante nueva información disponible o al requerimiento de profesionales, pacientes, productores y/o gestores.


Assuntos
Humanos , Receptores de Epoprostenol/agonistas , Hipertensão Pulmonar/tratamento farmacológico , Avaliação da Tecnologia Biomédica , Avaliação em Saúde , Análise Custo-Benefício
14.
Med Hypotheses ; 143: 110142, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32759013

RESUMO

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.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Ácido Fólico/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Óxido Nítrico/metabolismo , Pandemias , Pneumonia Viral/complicações , Administração por Inalação , Animais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Ativação Enzimática/efeitos dos fármacos , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Humanos , Hipertensão Pulmonar/complicações , Hipóxia/tratamento farmacológico , Hipóxia/etiologia , Camundongos , Óxido Nítrico/administração & dosagem , Óxido Nítrico/uso terapêutico , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Taquifilaxia
15.
Am J Respir Cell Mol Biol ; 63(4): 510-518, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32609558

RESUMO

Optimal oxygen saturation as measured by pulse oximetry (SpO2) in neonatal lung injury, such as meconium aspiration syndrome (MAS) and persistent pulmonary hypertension of newborn (PPHN), is not known. Our goal was to determine the SpO2 range in lambs with MAS and PPHN that results in the highest brain oxygen delivery (bDO2) and pulmonary blood flow (Qp) and the lowest pulmonary vascular resistance and oxidative stress. Meconium was instilled into endotracheal tubes in 25 near-term gestation lambs, and the umbilical cord was occluded to induce asphyxia and gasping, causing MAS and PPHN. Lambs were randomized into four groups and ventilated for 6 hours with fixed fraction of inspired oxygen (FiO2) = 1.0 irrespective of SpO2, and three groups had FiO2 titrated to keep preductal SpO2 between 85% and 89%, 90% and 94%, and 95% and 99%, respectively. Tissues were collected to measure nitric oxide synthase activity, 3-nitrotyrosine, and 8-isoprostanes. Throughout the 6-hour exposure period, lambs in the 95-99% SpO2 target group had the highest Qp, lowest pulmonary vascular resistance, and highest bDO2 but were exposed to higher FiO2 (0.5 ± 0.21 vs. 0.29 ± 0.17) with higher lung 3-nitrotyrosine (0.67 [interquartile range (IQR), 0.43-0.73] ng/mcg protein vs. 0.1 [IQR, 0.09-0.2] ng/mcg protein) and lower lung nitric oxide synthase activity (196 [IQR, 192-201] mMol nitrite/mg protein vs. 270 [IQR, 227-280] mMol nitrite/mg protein) compared with the 90-94% target group. Brain 3-nitrotyrosine was lower in the 85-89% target group, and brain/lung 8-isoprostane levels were not significantly different. In term lambs with MAS and PPHN, Qp and bDO2 through the first 6 hours are higher with target SpO2 in the 95-99% range. However, the 90-94% target range is associated with significantly lower FiO2 and lung oxidative stress. Clinical trials comparing the 90-94% versus the 95-99% SpO2 target range in term infants with PPHN are warranted.


Assuntos
Hipertensão Pulmonar/metabolismo , Pulmão/metabolismo , Síndrome de Aspiração de Mecônio/metabolismo , Oxigênio/metabolismo , Animais , Animais Recém-Nascidos , Dinoprosta/análogos & derivados , Dinoprosta/farmacologia , Feminino , Hipertensão Pulmonar/tratamento farmacológico , Pulmão/efeitos dos fármacos , Masculino , Síndrome de Aspiração de Mecônio/tratamento farmacológico , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oximetria/métodos , Síndrome da Persistência do Padrão de Circulação Fetal/tratamento farmacológico , Síndrome da Persistência do Padrão de Circulação Fetal/metabolismo , Gravidez , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Ovinos/metabolismo , Tirosina/análogos & derivados , Tirosina/farmacologia , Resistência Vascular/efeitos dos fármacos
16.
Intern Med ; 59(13): 1621-1627, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612065

RESUMO

Pulmonary tumor thrombotic microangiopathy (PTTM) is an acute, progressive, and fatal disease. PTTM manifests as subacute respiratory failure with pulmonary hypertension, progressive right-sided heart failure, and sudden death. An antemortem diagnosis of PTTM is very difficult to obtain, and many patients die within several weeks. We herein report a case of PTTM diagnosed based on a transbronchial lung biopsy. In this case, we finally diagnosed PTTM due to gastric cancer because of its histological identity. The patient was administered chemotherapy, including angiogenesis inhibitors, against gastric cancer at an early age and survived for a long time.


Assuntos
Adenocarcinoma/complicações , Neoplasias Pulmonares/complicações , Pulmão/patologia , Neoplasias Gástricas/complicações , Microangiopatias Trombóticas/etiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Biópsia , Progressão da Doença , Evolução Fatal , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Microangiopatias Trombóticas/diagnóstico , Tomografia Computadorizada por Raios X
17.
Life Sci ; 257: 118001, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32634428

RESUMO

AIMS: Pulmonary hypertension (PH) is a severe and prevalent complication of chronic obstructive pulmonary disease (COPD), with low quality of life and poor prognosis. This study was designed to evaluate the efficacy and safety of Sildenafil in the treatment of PH caused by COPD (COPD-PH) and provide reference for clinical treatment. MATERIALS AND METHODS: We systematically searched PubMed, EMBASE, Cochrane Library, Clinical Trials.gov databases, Wanfang Data and CNKI for comprehensive literature reporting Sildenafil for randomized controlled trials (RCT) of COPD-PH. Quality assessment, data analysis used the modified Jadad scale and RevMan5.3 software. KEY FINDINGS: A total of 9 RCTs involving 579 patients were included in our study. The primary outcome measure was Six minutes walking distance (6MWD). Secondary observations were Pulmonary artery systolic pressure (PASP), Borg dyspnea index, and Survey scale (SF-36). Our data demonstrate that Sildenafil can improve 6WMD [29.64, 95% CI (13.78, 45.50), P < 0.00001] and PASP [-7.86, 95% CI (-11.26, -4.46) P < 0.00001] of COPD-PH, compared with the control group. However, SF-36 [2.64, 95% CI (-6.85, 12.14) P = 0.59] and Borg dyspnea index [-0.28, 95% CI (-1.08, 0.52) P = 0.49] have no significant difference between those two groups. Adverse reactions in the Sildenafil treatment group were tolerated headaches and digestive symptoms, which were relatively safe. SIGNIFICANCE: Available clinical evidence indicates that Sildenafil seems to be safe and effective for COPD-PH and can improve the patients' 6WMD. However, large-sample, high-quality multicenter RCTs are still needed to provide stronger evidence-based medical evidence.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Citrato de Sildenafila/uso terapêutico , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Citrato de Sildenafila/metabolismo , Resultado do Tratamento
18.
Vet Res Commun ; 44(2): 73-81, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32500313

RESUMO

BACKGROUND: Sildenafil improves autonomic dysfunction caused by pulmonary hypertension (PH) in humans, but its effect is unknown in dogs with PH. This prospective study aimed to evaluate the autonomic nervous system function of a canine model of chronic embolic PH (CEPH) and the autonomic nervous system function of a canine model of CEPH in which sildenafil was administered. METHODS: This study used five clinically healthy female beagle dogs. Evaluation parameters included hemodynamic parameters, heart rate (HR) and heart rate variability (HRV). Each evaluation parameter was compared before and after creating the CEPH model (before, BL; after, CEPHBL) and between the CEPHBL model and after the administration of sildenafil (1 mg/kg, BID) in the CEPH model dogs (CEPHSil). RESULTS: In the CEPHBL model, the hemodynamic parameters indicated cardiac hypofunction, and HR was significantly increased and HRV was significantly decreased compared with BL. Further, in the CEPHSil model, the hemodynamic parameters suggested improvement in cardiac function, and HRV was significantly increased. CONCLUSIONS: From the results of the CEPH model dogs, autonomic dysfunction was shown to occur in PH dogs. In addition, the administration of 1 mg/kg of sildenafil to CEPH model dogs may improve autonomic dysfunction.


Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Citrato de Sildenafila/administração & dosagem , Citrato de Sildenafila/farmacologia , Animais , Sistema Nervoso Autônomo/fisiopatologia , Doença Crônica , Modelos Animais de Doenças , Cães , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/fisiopatologia
19.
PLoS One ; 15(5): e0233063, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32442171

RESUMO

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, characterized by non-resolving fibro-thrombotic obstructions of large pulmonary arteries. Pulmonary endarterectomy (PEA) is the treatment of choice for the disease, significantly improving survival. Patients with worse hemodynamic profile have worse prognosis after surgery, raising the question of whether the use of medical therapy prior to surgery to optimize hemodynamics could improve outcomes. The aim of this study was to evaluate the role of medical therapy pre-PEA, according to the hemodynamic profile at the diagnosis. We retrospectively analyzed all patients submitted to PEA, from January 2013 to December 2017. Functional, clinical and hemodynamic data were collected to evaluate the main prognostic determinants. Patients were stratified according to the hemodynamic severity and use of targeted therapies prior to surgery. A total of 108 patients were included. Thirty-five patients (32,4%) used targeted therapy pre-PEA. The use of medical therapy delayed the surgical procedure by about 7 months. There was no difference in overall survival between patients that received targeted therapy and those treated only with supportive therapy (87.8% vs 80.3%, respectively, p = 0.426). Nevertheless, when analyzing the group of patients with severe hemodynamic impairment, defined by low cardiac output(<3.7L/min) at baseline, patients treated with targeted therapies presented a significantly better one-year survival. In higher-risk CTEPH patients, characterized by the presence of low cardiac output, the use of targeted therapies prior to PEA was associated with better outcome, suggesting a potential role for pre-operative use of medical treatment in this particular subgroup.


Assuntos
Endarterectomia/métodos , Antagonistas dos Receptores de Endotelina/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Adulto , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão Pulmonar/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Prognóstico , Embolia Pulmonar/cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
20.
Am J Respir Crit Care Med ; 202(6): 843-852, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32437637

RESUMO

Rationale: Pulmonary hypertension (PH) associated with neurofibromatosis type 1 (NF1) is a rare and largely unknown complication of NF1.Objectives: To describe characteristics and outcomes of PH-NF1.Methods: We reported the clinical, functional, radiologic, histologic, and hemodynamic characteristics, response to pulmonary arterial hypertension (PAH)-approved drugs, and transplant-free survival of patients with PH-NF1 from the French PH registry.Measurements and Main Results: We identified 49 PH-NF1 cases, characterized by a female/male ratio of 3.9 and a median (minimum-maximum) age at diagnosis of 62 (18-82) years. At diagnosis, 92% were in New York Heart Association functional class III or IV. The 6-minute-walk distance was 211 (0-460) m. Pulmonary function tests showed low DlCO (30% [12-79%]) and severe hypoxemia (PaO2 56 [38-99] mm Hg). Right heart catheterization showed severe precapillary PH with a mean pulmonary artery pressure of 45 (10) mm Hg and a pulmonary vascular resistance of 10.7 (4.2) Wood units. High-resolution computed tomography images revealed cysts (76%), ground-glass opacities (73%), emphysema (49%), and reticulations (39%). Forty patients received PAH-approved drugs with a significant improvement in functional class and hemodynamic parameters. Transplant-free survival at 1, 3, and 5 years was 87%, 54%, and 42%, respectively, and four patients were transplanted. Pathologic assessment showed nonspecific interstitial pneumonia and major pulmonary vascular remodeling.Conclusions: PH-NF1 is characterized by a female predominance, a low DlCO, and severe functional and hemodynamic impairment. Despite a potential benefit of PAH treatment, prognosis remains poor, and double-lung transplantation is an option for eligible patients.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/cirurgia , Neoplasias Pulmonares/fisiopatologia , Neurofibromatose 1/complicações , Neurofibromatose 1/genética , Neurofibromina 1/genética , Adolescente , Adulto , Feminino , França , Humanos , Hipertensão Pulmonar/etiologia , Transplante de Pulmão/métodos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Adulto Jovem
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