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1.
Eur Heart J ; 42(42): 4298-4305, 2021 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-34506618

RESUMEN

AIMS: This study aimed to assess the clinical characteristics and long-term survival outcome in patients with Takayasu's arteritis-associated pulmonary hypertension (TA-PH). METHODS AND RESULTS: We conducted a nationally representative cohort study of TA-PH using data from the National Rare Diseases Registry System of China. Patients with pulmonary artery involvement who fulfilled the diagnostic criteria of Takayasu's arteritis and pulmonary hypertension were included. The primary outcome was the time from diagnosis of TA-PH to the occurrence of all-cause death. Between January 2007 and January 2019, a total of 140 patients were included, with a mean age of 41.4 years at diagnosis, and a female predominance (81%). Patients with TA-PH had severely haemodynamic and functional impairments at diagnosis. Significant improvements have been found in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and haemodynamic profiles in patients with TA-PH receiving drugs approved for pulmonary arterial hypertension. The overall 1-, 3-, and 5-year survival rates in TA-PH were 94.0%, 83.2%, and 77.2%, respectively. Predictors associated with an increased risk of all-cause death were syncope [adjusted hazard ratio (HR) 5.38 (95% confidence interval 1.77-16.34), P = 0.003], NT-proBNP level [adjusted HR 1.04 (1.03-1.06), P < 0.001], and mean right atrial pressure [adjusted HR 1.07 (1.01-1.13), P = 0.015]. CONCLUSION: Patients with TA-PH were predominantly female and had severely compromised haemodynamics. More than 80% of patients in our cohort survived for at least 3 years. Medical treatment was based on investigators' personal opinions, and no clear risk-to-benefit ratio can be derived from the presented data.


Asunto(s)
Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Arteritis de Takayasu , Adulto , Estudios de Cohortes , Femenino , Humanos , Hipertensión Pulmonar/etiología , Estudios Retrospectivos , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/epidemiología
2.
Eur Heart J ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39101604
3.
Cardiovasc Toxicol ; 24(9): 879-888, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39008240

RESUMEN

This study aimed to evaluate the correlation of plasma deoxycholic acid (DCA) levels with clinical and hemodynamic parameters in acute pulmonary embolism (APE) patients. Total 149 APE adult patients were prospectively recruited. Plasma DCA levels were measured using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry. Baseline clinical and hemodynamic parameters were evaluated according to plasma DCA levels. The plasma DCA levels were significantly lower in APE patients than in those without APE (P < 0.001). APE patients with adverse events had lower plasma DCA levels (P < 0.001). Low DCA group patients presented more adverse cardiac function, higher NT-proBNP levels (P = 0.010), and higher WHO functional class levels (P = 0.023). Low DCA group also presented with an adverse hemodynamic status, with higher pulmonary vascular resistance levels (P = 0.027) and lower cardiac index levels (P = 0.024). Both cardiac function and hemodynamic parameters correlated well with plasma DCA levels. Kaplan-Meier survival analysis demonstrated that APE patients with lower plasma DCA levels had a significantly higher event rate (P = 0.009). In the univariate and multivariate Cox regression analyses, the plasma DCA level was an independent predictor of clinical worsening events after adjusting for age, sex, WHO functional class, NT-proBNP level, pulmonary vascular resistance, and cardiac index (HR 0.370, 95% CI 0.161, 0.852; P = 0.019). Low plasma DCA levels predicted adverse cardiac function and hemodynamic collapse. A low DCA level was correlated with a higher clinical worsening event rate and could be an independent predictor of clinical outcomes in multivariate analysis.


Asunto(s)
Biomarcadores , Ácido Desoxicólico , Hemodinámica , Embolia Pulmonar , Humanos , Embolia Pulmonar/sangre , Embolia Pulmonar/fisiopatología , Embolia Pulmonar/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Biomarcadores/sangre , Factores de Riesgo , Ácido Desoxicólico/sangre , Enfermedad Aguda , Pronóstico , Medición de Riesgo , Valor Predictivo de las Pruebas , Péptido Natriurético Encefálico/sangre , Adulto , Fragmentos de Péptidos/sangre
4.
Heart Vessels ; 27(6): 603-9, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21927863

RESUMEN

We investigated the short-term and medium-term results in patients with pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) undergoing transcatheter closure. Fifteen patients with severe PAH associated with ASD who underwent successful occluder implantation from 2007 to 2010 were included. Clinical, echocardiographic, and hemodynamic data were reviewed. Severe PAH was defined as pulmonary arterial systolic pressure measured by catheterization was ≥60 mmHg and pulmonary vascular resistance (PVR) ≥6 Wood Units (WU). Compared with baseline, the 6-minwalking distance significantly increased by 29.7 ± 26.3 m (P < 0.001) at 3 months (short-term) and 65.4 ± 63.6 m (P < 0.001) at 23.4 ± 9.7 months (medium-term), World Health Organization function class considerably improved after postclosure short-term and medium-term. Repeat cardiac catheterization (n = 7) showed that mean pulmonary arterial pressure decreased from 51.6 ± 9.4 mmHg at baseline to 21.0 ± 3.8 mmHg (P < 0.001) at follow-up of 12 months. The PVR decreased by 5.6 ± 1.1 WU (P < 0.001). Through carefully selected patients with severe PAH associated with ASD, transcatheter closure can be safely performed with a promising short-term and medium-term outcome. Trial occlusion is an effective way for deciding the reversibility of severe PAH in ASD patients. The role of aerosolized iloprost for pulmonary vasoreactivity testing in patients with severe PAH secondary to ASD requires further investigation.


Asunto(s)
Cateterismo Cardíaco/instrumentación , Hipertensión Pulmonar/etiología , Dispositivo Oclusor Septal , Administración por Inhalación , Adulto , Aerosoles , Anciano , Presión Arterial , Cateterismo Cardíaco/efectos adversos , Cateterismo de Swan-Ganz , Distribución de Chi-Cuadrado , Prueba de Esfuerzo , Tolerancia al Ejercicio , Hipertensión Pulmonar Primaria Familiar , Femenino , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/fisiopatología , Defectos del Tabique Interatrial/terapia , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/fisiopatología , Iloprost/administración & dosificación , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Recuperación de la Función , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía , Resistencia Vascular , Caminata , Adulto Joven
5.
Am J Respir Crit Care Med ; 183(12): 1723-9, 2011 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-21471085

RESUMEN

RATIONALE: Although the phosphodiesterase type 5 inhibitors sildenafil and tadalafil have demonstrated efficacy in patients with pulmonary arterial hypertension (PAH), monotherapy with these agents has not been conclusively shown to reduce clinical worsening events. OBJECTIVES: To evaluate the safety and efficacy of the phosphodiesterase type 5 inhibitor vardenafil in Chinese patients with PAH. METHODS: In a randomized, double-blind, placebo-controlled study, 66 patients with PAH were randomized 2:1 to vardenafil (5 mg once daily for 4 wk then 5 mg twice daily; n = 44) or placebo (n = 22) for 12 weeks. Patients completing this phase were then treated with open-label vardenafil (5 mg twice daily) for a further 12 weeks. MEASUREMENTS AND MAIN RESULTS: At Week 12, the mean placebo-corrected 6-minute walking distance was increased with vardenafil (69 m; P < 0.001), and this improvement was maintained for at least 24 weeks. Vardenafil also increased the mean placebo-corrected cardiac index (0.39 L·min(-1)·m(-2); P = 0.005) and decreased mean pulmonary arterial pressure and pulmonary vascular resistance (-5.3 mm Hg, P = 0.047; -4.7 Wood U, P = 0.003; respectively) at Week 12. Four patients in the placebo group (20%) and one in the vardenafil group (2.3%) had clinical worsening events (hazard ratio 0.105; 95% confidence interval, 0.012-0.938; P = 0.044). Vardenafil was associated with only mild and transient adverse events. CONCLUSIONS: Vardenafil is effective and well tolerated in patients with PAH at a dose of 5 mg twice daily.


Asunto(s)
Hipertensión Pulmonar/tratamiento farmacológico , Imidazoles/uso terapéutico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Piperazinas/uso terapéutico , Vasodilatadores/uso terapéutico , Adolescente , Adulto , Método Doble Ciego , Femenino , Corazón , Humanos , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Presorreceptores/efectos de los fármacos , Circulación Pulmonar/efectos de los fármacos , Sulfonas/uso terapéutico , Resultado del Tratamiento , Triazinas/uso terapéutico , Diclorhidrato de Vardenafil , Resistencia Vascular/efectos de los fármacos , Caminata
6.
Zhonghua Yi Xue Za Zhi ; 91(6): 370-4, 2011 Feb 15.
Artículo en Zh | MEDLINE | ID: mdl-21418907

RESUMEN

OBJECTIVE: Sildenafil has been shown to be effective in pulmonary arterial hypertension (PAH). However, the impact of sildenafil on PAH has been under-investigated in China. The aim of the present study was to evaluate the efficacy and safety of oral sildenafil in PAH patients in China. METHODS: In this prospective, open-label and multi-center study, 90 patients were recruited from 14 centers to receive oral sildenafil (75 mg/d) for 12 weeks. They underwent a six-minute walk test (SMWT) and cardiac catheterization at the beginning and the end of 12 weeks. The primary endpoint was the changes in exercise capacity as assessed by SMWT. And the secondary endpoints included assessment of functional class, evaluation of cardiopulmonary hemodynamics and clinical deterioration (defined as death, transplantation and re-hospitalization for PAH). Drug safety and tolerability were also examined. RESULTS: There were 19 males and 71 females with an average age of 32.5 ± 12.1 years old (range: 18 - 61). Their etiologies were idiopathic (n = 15), related with congenital heart disease (n = 60), or related with connective tissue disease (n = 9) and chronic thromboembolic pulmonary hypertension (n = 6). Oral sildenafil significantly increased the SMWT distances [(342 ± 93) m vs. (403 ± 88) m, P < 0.001]. There was also remarkable improvement in Borg dyspnea score (2.9 ± 2.6 vs. 2.4 ± 2.0, P = 0.005). Furthermore, significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also found (mean pulmonary artery pressure, P < 0.001; cardiac index, P < 0.001; pulmonary vascular resistance, P < 0.001). Side effects were mild and consistent with other reports. CONCLUSION: This study confirms and extends previous studies. Oral sildenafil is both safe and effective for the treatment of adult PAH patients in China.


Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Piperazinas/uso terapéutico , Sulfonas/uso terapéutico , Adolescente , Adulto , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Estudios Prospectivos , Purinas/administración & dosificación , Purinas/efectos adversos , Purinas/uso terapéutico , Citrato de Sildenafil , Sulfonas/administración & dosificación , Sulfonas/efectos adversos , Resultado del Tratamiento , Adulto Joven
7.
Zhonghua Xin Xue Guan Bing Za Zhi ; 39(2): 124-7, 2011 Feb.
Artículo en Zh | MEDLINE | ID: mdl-21426745

RESUMEN

OBJECTIVE: To investigate the efficacy, safety and tolerance of bosentan, a dual endothelin receptor antagonist, in Chinese patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS: Totally 79 IPAH patients (hemodynamic criteria confirmed by right heart catheterization) were included in this open-label, prospective multicenter study. Patients received 62.5 mg of bosentan twice daily for the first 4 weeks, and then up-titrated to 125 mg twice daily for another 12 weeks. The primary end point was the change in exercise capacity showed by six-minute walk distance (6MWD) from baseline to 16 weeks. Secondary end points included the change in World Health Organization (WHO) functional class, Borg dyspnoea scale and systolic pulmonary artery pressure measured by echocardiography. RESULTS: The 6MWD increased from (343.7 ± 93.7) meters at baseline to (397.5 ± 104.4) meters after 16 weeks (P < 0.01), WHO functional class and Borg dyspnoea scale were also significantly improved after 16 weeks therapy compared to baseline levels (all P < 0.01). Furthermore, the systolic pulmonary artery pressure was significantly decreased from (97.8 ± 25.2) mm Hg (1 mm Hg = 0.133 kPa) to (92.8 ± 29.5) mm Hg (P < 0.05) after 16 weeks bosentan treatment. There was no patient withdrawal from this study for safety consideration. CONCLUSION: Bosentan therapy is well tolerated and can improve the exercise capacity and WHO functional class in Chinese IPAH patients.


Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Adolescente , Adulto , Anciano , Antihipertensivos/efectos adversos , Pueblo Asiatico , Bosentán , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sulfonamidas/efectos adversos , Adulto Joven
9.
Chest ; 150(2): 367-73, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27001265

RESUMEN

BACKGROUND: This study aimed to show whether circulating bone morphogenetic proteins (BMPs) levels are associated with increased risk of mortality in patients with pulmonary arterial hypertension (PAH). METHODS: A total of 156 patients with PAH including 43 with heritable PAH (HPAH) and 113 with idiopathic PAH (IPAH) diagnosed by gene screening were enrolled in the study. Circulating BMPs were measured by ELISA in plasma samples from patients with HPAH (n = 43) and IPAH (n = 113) and from control subjects (n = 51). Clinical characteristics at baseline and long-term survival were compared according to the different BMP levels. RESULTS: Patients with HPAH had significantly higher BMP7 concentrations than patients with IPAH and control subjects (20.1 [interquartile range (IQR), 9.4, 55.2] vs 6.5 [IQR, 3.5, 11.7] and 2.5 [IQR, 0.9, 6.6] pg/mL, respectively; P < .001). Elevated plasma BMP7 were associated with a higher risk of mortality after adjustment for sex, 6-minute walk distance, mean right atrial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output (HR, 1.904; 95% CI, 1.021-3.551; P = .043). Patients with IPAH with a BMP7 level > 7.85 pg/mL had a higher risk of mortality than those with a low BMP7 concentration (P = .042, log-rank test). CONCLUSIONS: Levels of circulating BMP7 correlate with mortality in PAH, and may be a predictor of disease in patients with HPAH and IPAH.


Asunto(s)
Proteína Morfogenética Ósea 7/sangre , Hipertensión Pulmonar Primaria Familiar/sangre , Adolescente , Adulto , Gasto Cardíaco , Hipertensión Pulmonar Primaria Familiar/mortalidad , Hipertensión Pulmonar Primaria Familiar/fisiopatología , Femenino , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/mortalidad , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Presión Esfenoidal Pulmonar , Curva ROC , Factores Sexuales , Resistencia Vascular , Prueba de Paso , Adulto Joven
10.
J Clin Pharmacol ; 52(3): 425-31, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21415281

RESUMEN

The impact of sildenafil on pulmonary arterial hypertension (PAH) in Chinese patients has been less investigated. A prospective, open-label, uncontrolled and multicenter study, therefore, was carried out to address this issue. Ninety patients with multicause-induced PAH received oral sildenafil (75 mg/day) for 12 weeks. The 6-minute walk test (SMWT) and cardiac catheterization were performed at the beginning and the end of the 12 weeks. The primary endpoint was the changes in exercise capacity assessed by the SMWT; the secondary endpoint included assessment of functional class, evaluation of cardiopulmonary hemodynamics, and clinical worsening. Drug safety and tolerability were also examined. The results showed that there was a significant improvement in SMWT distances (342 ± 93 m vs 403 ± 88 m, P < .0001), Borg dyspnea score (2.9 ± 2.6 vs 2.4 ± 2.0, P = .0046), World Health Organization functional class, and cardiopulmonary hemodynamics (mean pulmonary artery pressure, P < .0001; cardiac index, P < .0001; pulmonary vascular resistance, P < .0001) after 12 weeks of oral sidenafil therapy. Almost all enrolled patients did not experience significant clinical worsening. This study confirms and extends the findings of previous studies relating to effects of sildenafil on PAH, suggesting that oral sildenafil is safe and effective for the treatment of adult patients with PAH in the Chinese population.


Asunto(s)
Hipertensión Pulmonar/tratamiento farmacológico , Piperazinas/uso terapéutico , Sulfonas/uso terapéutico , Vasodilatadores/uso terapéutico , Administración Oral , Adulto , China/epidemiología , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , Hipertensión Pulmonar/epidemiología , Masculino , Piperazinas/efectos adversos , Purinas/efectos adversos , Purinas/uso terapéutico , Citrato de Sildenafil , Sulfonas/efectos adversos , Vasodilatadores/efectos adversos , Adulto Joven
11.
Chest ; 140(2): 301-309, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21330386

RESUMEN

BACKGROUND: In a previous study of Chinese patients with idiopathic pulmonary arterial hypertension (IPAH) in the nontargeted therapy era (defined as the time before 2006 when new pulmonary arterial hypertension-specific drugs were not available in China), we reported 1- and 3-year survival estimates of only 68% and 39%, respectively. However, it is not yet known whether the survival of patients with pulmonary arterial hypertension is improved in the modern treatment era (defined in China as after 2006). METHODS: A retrospective cohort study was undertaken in 276 consecutive patients with newly diagnosed incident IPAH and connective tissue disease-related pulmonary arterial hypertension (CTDPAH) who were referred between 2007 and 2009. Baseline characteristics and survival rates in the two groups were compared. RESULTS: The 1- and 3-year survival estimates were 92.1% and 75.1%, respectively, in patients with IPAH, and 85.4% and 53.6%, respectively, in patients with CTDPAH. Patients with CTDPAH had a significantly lower mean pulmonary artery pressure, more pericardial effusion, and more severe impairment of the diffusion capacity of the lung for carbon monoxide than patients with IPAH. A diagnosis of CTDPAH, World Health Organization functional class III or IV, single-breath diffusion capacity of the lung for carbon monoxide < 80% predicted, and the presence of pericardial effusion were independent predictors of mortality. The 1- and 3-year survival rates of male patients were 93.5% and 77.5%, respectively, in those with IPAH, and 71.1% and 47.4%, respectively, in those with CTDPAH. CONCLUSIONS: The survival rates of patients with pulmonary arterial hypertension have improved in China in the modern treatment era, despite the high costs of treatment and financial constraints. However, the survival rates of patients with CTDPAH are inferior to those of patients with IPAH. Our study also indicates poorer survival rates in male patients with CTDPAH.


Asunto(s)
Hipertensión Pulmonar/mortalidad , Adulto , China/epidemiología , Estudios de Cohortes , Enfermedades del Tejido Conjuntivo/complicaciones , Ecocardiografía , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/fisiopatología , Masculino , Derrame Pericárdico/complicaciones , Pruebas de Función Respiratoria , Tasa de Supervivencia
12.
Heart ; 97(22): 1876-81, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21948962

RESUMEN

BACKGROUND: Although sildenafil has been shown to be safe and effective in idiopathic pulmonary arterial hypertension (PAH) and PAH related to connective tissue disease, its effects in Eisenmenger syndrome are less clear. OBJECTIVE: To investigate whether long-term treatment (12 months) with the phosphodiesterase type 5 inhibitor sildenafil improves clinical and haemodynamic parameters in patients with Eisenmenger syndrome. DESIGN: Prospective, open-label, multicentre study. SETTING: Four pulmonary hypertension centres in China. PATIENTS: 84 Eisenmenger syndrome functional class II-IV patients. INTERVENTIONS: Oral sildenafil 20 mg orally three times a day. OUTCOME MEASURES: 6-min walk distance (6MWD) test, resting systemic arterial blood oxygen saturation (SaO(2)) in room air, haemodynamic parameters assessed by right heart catheterisation, safety and tolerability. RESULTS: The overall treatment effects at 12 months versus baseline (mean changes with 95% CIs) were 56 m increase (42 to 69, p<0.0001) in 6MWD, and 2.4% increase (1.8% to 2.9%, p<0.0001) in resting room air SaO(2). Improvements were also seen in mean pulmonary arterial pressure and pulmonary vascular resistance index (-4.7 mm Hg (-7.5 to -1.9), p=0.001; and -474 dyn×s×cm(-5)×m(2) (-634 to -314), p<0.0001, respectively). Sildenafil was well tolerated. Most adverse events were mild and transient, and occurred in the first 2 weeks of treatment. CONCLUSIONS: Twelve months of oral sildenafil treatment was well tolerated and appeared to improve exercise capacity, systemic arterial oxygen saturation and haemodynamic parameters in patients with Eisenmenger syndrome.


Asunto(s)
Complejo de Eisenmenger/tratamiento farmacológico , Piperazinas/uso terapéutico , Sulfonas/uso terapéutico , Vasodilatadores/uso terapéutico , Administración Oral , Adolescente , Adulto , China , Esquema de Medicación , Complejo de Eisenmenger/diagnóstico , Tolerancia al Ejercicio , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Piperazinas/farmacología , Estudios Prospectivos , Purinas/administración & dosificación , Purinas/farmacología , Purinas/uso terapéutico , Índice de Severidad de la Enfermedad , Citrato de Sildenafil , Sulfonas/administración & dosificación , Sulfonas/farmacología , Resultado del Tratamiento , Vasodilatadores/administración & dosificación , Vasodilatadores/farmacología
13.
Int J Mol Med ; 26(4): 541-7, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20818494

RESUMEN

Statins have recently come under evaluation for the treatment of pulmonary arterial hypertension (PAH). The aim of this study was to examine the effects of atorvastatin on the clinical manifestations and expression of p38, p27 and Jab1 using a rat PAH model. Ninety-six male Wistar rats were divided into control (receiving no surgical treatment), vehicle and treatment groups, among which the last two groups underwent left pneumonectomy and were then treated with monocrotaline (MCT, 60 mg/kg). Both control and vehicle groups subsequently received saline, and the treatment group received atorvastatin (20 mg/kg) by stomach catheter. Rats were sacrificed, and mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. The expression of p38, p27, and Jab1 was evaluated by immunohistochemistry and Western blotting. At 28 days, mPAP and RVHI and expression levels of Jab1 and p38 in the vehicle group were significantly higher than those in the treatment and control groups. However, the expression of p27 was lowest in the vehicle group among the three groups. Atorvastatin reduced PAP and RVHI in the rat PAH model, decreased expression of p38 and Jab1 but increased expression of p27.


Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Antígeno Nuclear de Célula en Proliferación/genética , Proteínas/genética , Pirroles/uso terapéutico , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Animales , Atorvastatina , Complejo del Señalosoma COP9 , Ácidos Heptanoicos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/patología , Péptidos y Proteínas de Señalización Intracelular , Masculino , Monocrotalina , Neumonectomía , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/patología , Pirroles/farmacología , Ratas , Ratas Wistar
14.
Cardiovasc Ther ; 28(6): 350-5, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20637015

RESUMEN

BACKGROUND: It has been demonstrated that sildenafil is effective in patients with pulmonary arterial hypertension (PAH). However, the impact of sildenafil on PAH in adults with congenital heart disease (CHD) has been less investigated. OBJECTIVE: In this prospective, open-label, uncontrolled and multicenter study, 60 patients with PAH related to CHD received oral sildenafil (75 mg/day) for 12 weeks. The enrolled patients underwent six-minute walk test (SMWT) and cardiac catheterization at the beginning and the end of the 12 weeks. The primary end point was the changes in exercise capacity assessed by SMWT; the secondary end point included assessment of functional class, evaluation of cardiopulmonary hemodynamics, and clinical worsening (defined as death, transplantation, and rehospitalization for PAH). Drug safety and tolerability were also examined. RESULTS: Oral sidenafil significantly increased SMWT distances (422.94 ± 76.95 m vs. 371.99 ± 78.73 m, P < 0.0001). There was also remarkable improvement in Borg dyspnea score (2.1 ± 1.32 vs. 2.57 ± 1.42, P = 0.0307). Moreover, significant improvements in World Healthy Organization (WHO) functional class and cardiopulmonary hemodynamics were also discovered (mean pulmonary artery pressure, P = 0.0002; cardiac index, P < 0.0001; pulmonary vascular resistance, P < 0.0001). Side effects in this study were mild and consistent with reported studies. None of the enrolled patients experienced significant clinical worsening. CONCLUSIONS: This study confirmed and extended previous studies. It suggested that oral sildenafil was safe and effective for the treatment of adult patients with CHD-related PAH.


Asunto(s)
Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Cardiopatías Congénitas/complicaciones , Piperazinas/uso terapéutico , Sulfonas/uso terapéutico , Vasodilatadores/uso terapéutico , Administración Oral , Adolescente , Adulto , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Cateterismo Cardíaco , China , Esquema de Medicación , Disnea/tratamiento farmacológico , Disnea/etiología , Disnea/fisiopatología , Prueba de Esfuerzo , Tolerancia al Ejercicio/efectos de los fármacos , Hipertensión Pulmonar Primaria Familiar , Femenino , Cardiopatías Congénitas/fisiopatología , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Masculino , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Estudios Prospectivos , Purinas/administración & dosificación , Purinas/efectos adversos , Purinas/uso terapéutico , Citrato de Sildenafil , Sulfonas/administración & dosificación , Sulfonas/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Resistencia Vascular/efectos de los fármacos , Vasodilatadores/administración & dosificación , Vasodilatadores/efectos adversos , Adulto Joven
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