Is sildenafil an effective therapy in the management of persistent pulmonary hypertension?

Yaseen, Hakam; Darwich, Maha; Hamdy, Hossam

doi:10.4103/2249-4847.105958

Cited by 25 publications

(20 citation statements)

References 23 publications

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“…It has also been administered in pulmonary hypertension settings with favorable outcomes [20, 47]. Literature is very scarce, if any, regarding the use of sildenafil in the setting of liver I/R injury.…”

Section: Discussionmentioning

confidence: 99%

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

Savvanis

Nastos

Tasoulis

et al. 2014

Oxidative Medicine and Cellular Longevity

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We evaluated the role of sildenafil in a rat liver ischemia-reperfusion model. Forty male rats were randomly allocated in four groups. The sham group underwent midline laparotomy only. In the sildenafil group, sildenafil was administered intraperitoneally 60 minutes before sham laparotomy. In the ischemia-reperfusion (I/R) group, rats were subjected to 45 minutes of hepatic ischemia followed by 120 minutes of reperfusion, while in the sild+I/R group rats were subjected to a similar pattern of I/R after the administration of sildenafil, 60 minutes before ischemia. Two hours after reperfusion, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured and histopathological examination of the lobes subjected to ischemia as well as TUNEL staining for apoptotic bodies was performed. Additionally, myeloperoxidase (MPO) activity and the expression of intercellular adhesion molecule-1 (ICAM-1) were analyzed. Serum markers of hepatocellular injury were significantly lower in the sild+I/R group, which also exhibited lower severity of histopathological lesions and fewer apoptotic bodies, as compared to the I/R group. The I/R group showed significantly higher MPO activity and higher expression of ICAM-1, as compared to the sild+I/R group. Use of sildenafil as a preconditioning agent in a rat model of liver I/R exerted a protective effect.

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Section: Discussionmentioning

confidence: 99%

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

Savvanis

Nastos

Tasoulis

et al. 2014

Oxidative Medicine and Cellular Longevity

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“…Sildenafil also reduces inflammation, improves early postnatal survival, prevents pulmonary vascular remodeling in different experimental animal models of pulmonary hypertension without CDH (4,37,52), and prolongs survival and improves lung structure in a neonatal hyperoxia rat model (8). It has been successfully used in the postnatal treatment of persistent pulmonary hypertension of the newborn (PPHN) (2,15,28,36,45,50) and pulmonary hypertension in patients with congenital heart disease (43). There are no randomized controlled trials of sildenafil in patients with CDH, but there are case reports showing positive effects after postnatal treatment (3,26).…”

mentioning

confidence: 99%

Clinically relevant timing of antenatal sildenafil treatment reduces pulmonary vascular remodeling in congenital diaphragmatic hernia

Mous

Kool

Kempen

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Patients with congenital diaphragmatic hernia (CDH) suffer from severe pulmonary hypertension attributable to altered development of the pulmonary vasculature, which is often resistant to vasodilator therapy. Present treatment starts postnatally even though significant differences in the pulmonary vasculature are already present early during pregnancy. We examined the effects of prenatal treatment with the phosphodiesterase-5 inhibitor sildenafil on pulmonary vascular development in experimental CDH starting at a clinically relevant time. The well-established, nitrofen-induced CDH rodent model was treated daily with 100 mg/kg sildenafil from day 17.5 until day 20.5 of gestation (E17.5-20.5). Importantly, this timing perfectly corresponds to the developmental stage of the lung at 20 wk of human gestation, when CDH is detectable by 2D-ultrasonography and/or MRI. At E21.5 pups were delivered by caesarean section and euthanized by lethal injection of pentobarbital. The lungs were isolated and subsequently analyzed using immunostaining, real-time PCR, and volume measurements. Prenatal treatment with sildenafil improved lung morphology and attenuated vascular remodeling with reduced muscularization of the smaller vessels. Pulmonary vascular volume was not affected by sildenafil treatment. We show that prenatal treatment with sildenafil within a clinically relevant period improves pulmonary vascular development in an experimental CDH model. This may have important implications for the management of this disease and related pulmonary vascular diseases in human.

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“…cGMP effects are fleeting and swiftly degraded by local phosphodiesterases. Withdrawal of iNO can potentiate pulmonary vasoconstriction until the biological restoration of cGMP 7 8. Sildenafil is a phosphodiesterase inhibitor, selective for isoform 5, predominant in the lung.…”

Section: Commentarymentioning

confidence: 99%

In the child with pulmonary hypertension, does treatment with enteral sildenafil compared with a slow wean from nitric oxide alone prevent rebound pulmonary hypertension and allow for discontinuation of nitric oxide?

et al. 2019

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Is sildenafil an effective therapy in the management of persistent pulmonary hypertension?

Cited by 25 publications

References 23 publications

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

Clinically relevant timing of antenatal sildenafil treatment reduces pulmonary vascular remodeling in congenital diaphragmatic hernia

In the child with pulmonary hypertension, does treatment with enteral sildenafil compared with a slow wean from nitric oxide alone prevent rebound pulmonary hypertension and allow for discontinuation of nitric oxide?

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