Sildenafil, pulmonary hypertension and bronchopulmonary dysplasia

Herbert, Sophie; Tulloh, Robert

doi:10.1016/j.earlhumdev.2016.09.009

Cited by 9 publications

(10 citation statements)

References 28 publications

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“…In preterm infants, severe BPD is often complicated by PH which remains a significant cause of mortality and morbidity [ 7 ]. The vascular pathology of PH in BPD consists of both decreased vascularization and increased pulmonary vascular remodeling [ 4 – 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…The decreased vascular formation and increased vascular remodeling can lead to the development of pulmonary hypertension (PH) [ 4 – 6 ]. The mortality rate of severe BPD complicated with PH is as high as 50% [ 7 ]. Unfortunately, there is no effective therapy for BPD with PH due to its multifactorial etiology and poorly understood disease processes that impact not only alveolar structure but also the vasculature.…”

Section: Introductionmentioning

confidence: 99%

“…Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE-5) which increases levels of cGMP by preventing its degradation. Sildenafil is used off-label for more long-term management of PH in BPD since it is available in both IV and oral forms [ 7 ]. However, at the current time there is no formal evidence from randomized controlled trials supporting the benefit of sildenafil in BPD with PH.…”

Section: Introductionmentioning

confidence: 99%

“…Thus the Food and Drug Administration (FDA) has issued an warning for its judicious use in children with PH [ 13 ]. Other potential vasodilators such as bosentan, an antagonist of the endothelin receptor, and iloprost, a prostacyclin analogue that stimulates adenylate cyclase and increases cAMP have been used to treat BPD with PH in small case reports [ 7 ]. Because of limited options available, severe BPD with PH still remains a common and fatal disease in premature babies.…”

Section: Introductionmentioning

confidence: 99%

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Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

et al. 2018

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Bronchopulmonary dysplasia (BPD) remains the most common and serious chronic lung disease of premature infants. Severe BPD complicated with pulmonary hypertension (PH) increases the mortality of these infants. Riociguat is an allosteric soluble guanylate cyclase stimulator and is approved by the FDA for treating PH in adults. However, it has not been approved for use in neonates due to concern for adverse effects on long bone growth. To address this concern we investigated if administration of riociguat is beneficial in preventing hyperoxia-induced lung injury and PH without side effects on long bone growth in newborn rats. Newborn rats were randomized to normoxia (21% O2) or hyperoxia (85% O2) exposure groups within 24 hours of birth, and received riociguat or placebo by once daily intraperitoneal injections during continuous normoxia or hyperoxia exposure for 9 days. In the hyperoxia control group, radial alveolar count, mean linear intercept and vascular density were significantly decreased, the pathological hallmarks of BPD, and these were accompanied by an increased inflammatory response. There was also significantly elevated vascular muscularization of peripheral pulmonary vessels, right ventricular systolic pressure and right ventricular hypertrophy indicating PH. However, administration of riociguat significantly decreased lung inflammation, improved alveolar and vascular development, and decreased PH during hyperoxia by inducing cGMP production. Additionally, riociguat did not affect long bone growth or structure. These data indicate that riociguat is beneficial in preventing hyperoxia-induced lung injury and PH without affecting long bone growth and structure and hence, suggests riociguat may be a potential novel agent for preventing BPD and PH in neonates.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

et al. 2018

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“…(102) en TABLA 10. Potenciales efectos deletéreos de la hipercarbia POTENCIALES EFECTOS DELETÉREOS DE LA PACO 2 ELEVADA SOBRE EL APARATO RESPIRATORIO…”

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Recomendaciones del VIII Consenso Clínico de SIBEN para la Displasia Broncopulmonar

Sola¹,

Fariña²,

Mir³

et al. 2018

NeoReviews

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Dr Sola has disclosed that he is the Vice President of Medical Affairs with Masimo Corporation. Drs Fariña and Mir have disclosed no financial relationships relevant to the article. Dr Golombek has disclosed that he is on the speakers' bureau with Mallinckrodt and a consultant with Prolacta. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. El Dr Sola es VP de Medical Affairs de Masimo Corporation. Los Dres. Fariña y Mir declaran ausencia de conflicto de interés. El Dr Golombek pertenece al Speakers' Bureau de Mallinckrodt, y es Consultor de Prolacta. Este artículo no contiene una discusión sobre el uso no aprobado / investigativo de un producto / dispositivo comercial. En este Consenso participaron 48 profesionales de 12 países de Latinoamérica y España. La coordinación y revisión estuvo a cargo de los investigadores principales Dres. Fariña, Mir y Sola quienes han condensado todo el material trabajado. Los participantes del Consenso por orden alfabético fueron:

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Nanostructured lipid carriers versus solid lipid nanoparticles for the potential treatment of pulmonary hypertension via nebulization

Nafee

Makled

Boraie

2018

European Journal of Pharmaceutical Sciences

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Sildenafil, pulmonary hypertension and bronchopulmonary dysplasia

Cited by 9 publications

References 28 publications

Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

Riociguat prevents hyperoxia-induced lung injury and pulmonary hypertension in neonatal rats without effects on long bone growth

Recomendaciones del VIII Consenso Clínico de SIBEN para la Displasia Broncopulmonar

Nanostructured lipid carriers versus solid lipid nanoparticles for the potential treatment of pulmonary hypertension via nebulization

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