Sildenafil for primary and secondary pulmonary hypertension

Watanabe, Hiroshi; Ohashi, Kyoichi; Takeuchi, Kazuhiko; Yamashita, Kazuhiro; Yamaguchi, Taku; Tran, Quang‐Kim; Satoh, Hiroshi; Terada, Hajime; Ohashi, Hiroyuki; Hayashi, Hideharu

doi:10.1067/mcp.2002.123554

Cited by 85 publications

(57 citation statements)

References 6 publications

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“…As a vasodilator with good hemodynamic effects, sildenafil has been successfully used in the treatment of patients with pulmonary arterial hypertension (Sheth et al, 2005;Lopez-Guarch et al, 2004;Kataoka et al, 2004;Rosenkranz et al, 2004;Michelakis et al, 2003;Watanabe et al, 2002) and cardiovascular disease (Jackson et al, 2005;Cheitlin et al, 1999). By selectively inhibiting phosphodiesterase type-5 (PDE-5) and thus effectively reducing the breakdown of cGMP, sildenafil administration can markedly improve pulmonary and cardiac functional capacity, and hemodynamics (du Toit et al, 2005;Traverse et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Angiogenesis and improved cerebral blood flow in the ischemic boundary area detected by MRI after administration of sildenafil to rats with embolic stroke

Li¹,

Jiang²,

Zhang³

et al. 2007

Brain Research

106

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To dynamically investigate the long-term response of an ischemic lesion in rat brain to the administration of sildenafil, male Wistar rats subjected to embolic stroke were treated with sildenafil (n=11) or saline (n=10) at a dose of 10mg/Kg administered subcutaneously 24-hours after stroke and daily for an additional 6-days. Magnetic resonance images were acquired and functional performance was measured in all animals at 1-day, 2-days and weekly for 6-weeks post-stroke. All rats were sacrificed 6-weeks after stroke and endothelial barrier antigen immunostaining was employed for morphological analysis and quantification of cerebral vessels. Map-ISODATA was computed from T 1 , T 2 and T 1sat maps. ISODATA derived tissue signatures characterize the degree of ischemic injury. Based on the map-ISODATA calculated at 6-weeks, the ischemic lesion for each animal was divided into two specific regions, the ischemic boundary and ischemic core. The temporal profiles of cerebral blood flow (CBF) and tissue signature were retrospectively tracked in these two regions and were compared with histological evaluation and functional outcome. After 1-week of sildenafil treatment, the ischemic lesion exhibited two significantly different regions, with higher CBF level and correspondingly, lower tissue signature value in the boundary region than in the core region. Sildenafil treatment did not significantly reduce the lesion size, but did enhance angiogenesis. Functional performance was significantly increased after sildenafil treatment compared with the control group. Administration of sildenafil to rats with embolic stroke enhances angiogenesis and selectively increases the CBF level in the ischemic boundary, and improves neurological functional recovery compared to saline-treated rats.

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Section: Introductionmentioning

confidence: 99%

Angiogenesis and improved cerebral blood flow in the ischemic boundary area detected by MRI after administration of sildenafil to rats with embolic stroke

Li¹,

Jiang²,

Zhang³

et al. 2007

Brain Research

106

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“…(6) Michekalis et al (4) demonstraram que o sildenafil oral em dose única é um potente e seletivo vasodilatador pulmonar. O sildenafil foi também utilizado com resultados satisfatórios em dois casos descritos por Watanabe et al, (2) uma paciente portadora de HP primária e a segunda, de HP associada a doença difusa do tecido conjuntivo.…”

Section: Discussionunclassified

“…4 hipertensão pulmonar primária, a hipertensão pulmonar secundária também pode afetar significativamente a qualidade de vida e aproximar a morte em pacientes com doenças do tecido conjuntivo. (2) A associação de hipertensão pulmonar grave com a presença de anticorpos antifosfolipídios foi descrita pela primeira vez em 1983, quando 5 de 6 pacientes portadores de lúpus eritematoso e hipertensão pulmonar apresentaram anticoagulante lúpico positivo. A hipertensão pulmonar grave sintomática no lúpus eritematoso sistê-mico (LES) é rara e, quando presente, acarreta um prognóstico ruim, com resultados fatais que podem ocorrer em poucos meses, geralmente por colapso circulatório.…”

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Sildenafil no tratamento da hipertensão pulmonar associada a lúpus eritematoso sistêmico e síndrome antifosfolipídio

Souza

Garib

et al. 2003

J. Pneumologia

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Hipertensão pulmonar grave é uma doença debilitante, com expectativa de vida reduzida, que acomete adultos jovens. Complicações pleuropulmonares no lúpus eritematoso sistêmico ocorrem em 50% a 70% dos pacientes. A hipertensão pulmonar grave no lúpus eritematoso sistêmico é rara e tem prognóstico reservado. Descreve-se, pela primeira vez, um paciente com hipertensão pulmonar grave associada a lúpus eritematoso sistêmico e sín-drome antifosfolipídio secundário que apresentou boa resposta ao uso do sildenafil oral, após falha do tratamento convencional com corticosteróides, ciclofosfamida, warfarin e diltiazem. (J Pneumol 2003;29(5):302-4) Severe pulmonary hypertension is a debilitating disease with short life expectancy that often affects young people. Pleuropulmonary complications of systemic lupus erythematosus occur in 50-70% of patients. Severe symptomatic pulmonary hypertension in systemic lupus erythematosus is rare and carries a bad prognosis because a fatal outcome can occur within months. The authors describe, for the first time, a patient with systemic lupus erythematosus with severe pulmonary hypertension and secondary antiphospholipid syndrome who responded favorably to oral sildenafil, after unsuccessful use of prednisone, intravenous cyclophosphamide, warfarin and diltiazem.

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“…These results were compatible with the previously reported acute hemodynamic effects of sildenafil. [9][10][11] In any event, the long-term hemodynamic effects of sildenafil remain controversial, 9,11) and little is known about the potential role of sildenafil in long-term combination therapy.…”

Section: Discussionmentioning

confidence: 99%

Combination Therapy With Oral Sildenafil and Beraprost for Pulmonary Arterial Hypertension Associated With CREST Syndrome

et al. 2007

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SUMMARYPulmonary arterial hypertension (PAH) is commonly associated with CREST (Calcinosis, Raynaud phenomenon, Esophageal motility disorders, Sclerodactyly, and Telangiectasia) syndrome. Sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of PAH. However, little is known about the long-term hemodynamic effects of sildenafil, and the potential role of sildenafil in longterm combination with beraprost, an oral prostacyclin analogue, remains unclear. We therefore examined the hemodynamic effect of oral sildenafil alone and when coadministered with beraprost in a patient with PAH associated with CREST syndrome.Traces of the acute hemodynamic effects of beraprost (20 µg) disappeared after 2 hours. In contrast, the acute hemodynamic effects of sildenafil (50 mg) produced a greater reduction in PAP (31%) and PVR (40%), and these effects also disappeared after 5 hours.After 1 month of combination therapy of sildenafil (25 mg) twice daily and beraprost (20 µg) 3 times daily, the fall in pulmonary artery pressure and pulmonary vascular resistance was sustained (31% in both). Furthermore, the patient had significantly improved her 3-minute walk test and NYHA function class without significant adverse effects at the reported doses. The findings indicate that oral sildenafil is a potent pulmonary vasodilator that appears to act synergistically with oral beraprost to cause sustained pulmonary vasodilatation in a patient with PAH associated with CREST syndrome. (Int Heart J 2007; 48: 417-422) Key words: Pulmonary artery hypertension, CREST syndrome, Sildenafil, Beraprost PULMONARY artery hypertension (PAH) is a life-threatening disease characterized by progressive pulmonary hypertension that leads to right ventricular failure and death. 1) PAH comprises idiopathic PAH and PAH in the setting of collagen disease (eg, in localized cutaneous systemic sclerosis, also known as the From the

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Sildenafil for primary and secondary pulmonary hypertension

Abstract: The data strongly suggest that sildenafil can be used as a valuable pulmonary vasodilator in patients with pulmonary hypertension, with good long-term hemodynamic effects and safety. The results necessitate larger trials to confirm these observations in a larger cohort of patients.

Cited by 85 publications

References 6 publications

Angiogenesis and improved cerebral blood flow in the ischemic boundary area detected by MRI after administration of sildenafil to rats with embolic stroke

Angiogenesis and improved cerebral blood flow in the ischemic boundary area detected by MRI after administration of sildenafil to rats with embolic stroke

Sildenafil no tratamento da hipertensão pulmonar associada a lúpus eritematoso sistêmico e síndrome antifosfolipídio

Combination Therapy With Oral Sildenafil and Beraprost for Pulmonary Arterial Hypertension Associated With CREST Syndrome

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