PDE-5 inhibitors lower portal and pulmonary pressure in portopulmonary hypertension

Deibert, Peter; Bremer, Hinrich; Roêssle, M.; Ak, Kurz-Schmieg; Kreisel, Wolfgang

doi:10.1183/09031936.00110006

Cited by 15 publications

(9 citation statements)

References 7 publications

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“…(67) Phosphodiesterase-5 inhibitors decrease the hepatic sinusoidal resistance (68) but also increase the splanchnic blood flow, (69) accounting for the variable effects on the hepatic venous pressure gradient. (39,70,71) Riociguat reduced the portal pressure in an animal model of biliary cirrhosis, (72) but no data are available in humans.…”

Section: Effect Of Pah-specific Medications On Portal Hypertensionmentioning

confidence: 99%

Treatment Barriers in Portopulmonary Hypertension

2018

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Portopulmonary hypertension (PoPH) is a form of pulmonary arterial hypertension (PAH) that can develop as complication of portal hypertension. Treatment of PoPH includes PAH-specific therapies and in certain cases, such therapies are necessary to facilitate a successful liver transplantation. A significant number of barriers may limit the adequate treatment of patients with PoPH and explain the poorer survival of these patients when compared to other types of PAH. Until recently, only one randomized controlled trial has included PoPH patients and the majority of treatment data is derived from relatively small observational studies. In the present manuscript we review some of the barriers in the treatment of patients with PoPH and implications for liver transplantation. This article is protected by copyright. All rights reserved.

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Section: Effect Of Pah-specific Medications On Portal Hypertensionmentioning

confidence: 99%

Treatment Barriers in Portopulmonary Hypertension

2018

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“…In a previous clinical pilot study we showed that the PDE-5 inhibitor vardenafil increases portal venous flow in normal and cirrhotic liver and lowers portal pressure and hepatovenous pressure gradient in cirrhotics [37]. In a patient with portopulmonary hypertension we could further demonstrate that the PDE-5 inhibitor tadalafil lowers both pulmonary arterial and portal pressure [38]. Recently, Lee et al showed that after a standard dose of 50 mg sildenafil hepatic production of cyclic guanosine monophosphate increases leading to a significant decrease of hepatic sinusoid resistance (34).…”

Section: Introductionmentioning

confidence: 99%

Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver

et al. 2009

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BackgroundThe NO - cGMP system plays a key role in the regulation of sinusoidal tonus and liver blood flow with phosphodiesterase-5 (PDE-5) terminating the dilatory action of cGMP. We, therefore, investigated the effects of PDE-5 inhibitors on hepatic and systemic hemodynamics in rats.MethodsHemodynamic parameters were monitored for 60 min. after intravenous injection of sildenafil and vardenafil [1, 10 and 100 μg/kg (sil1, sil10, sil100, var1, var10, var100)] in anesthetized rats.ResultsCardiac output and heart rate remained constant. After a short dip, mean arterial blood pressure again increased. Systemic vascular resistance transiently decreased slightly. Changes in hepatic hemodynamic parameters started after few minutes and continued for at least 60 min. Portal (var10 -31%, sil10 -34%) and hepatic arterial resistance (var10 -30%, sil10 -32%) decreased significantly (p < 0.05). At the same time portal venous (var10 +29%, sil10 +24%), hepatic arterial (var10 +34%, sil10 +48%), and hepatic parenchymal blood flow (var10 +15%, sil10 +15%) increased significantly (p < 0.05). The fractional liver blood flow (total liver flow/cardiac output) increased significantly (var10 26%, sil10 23%). Portal pressure remained constant or tended to decrease. 10 μg/kg was the most effective dose for both PDE-5 inhibitors.ConclusionLow doses of phosphodiesterase-5 inhibitors have distinct effects on hepatic hemodynamic parameters. Their therapeutic use in portal hypertension should therefore be evaluated.

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“…Significant liver disease is generally an exclusion criterion in multicenter treatment trials in PAH 11, 16. There have been case reports and case series published on vasoactive therapy for POPH, but despite the recent data that 15% of patients at a PAH referral center had POPH, there is relatively limited information to guide clinicians' treatment of patients with POPH, particularly those with preserved cardiac output 12–14, 17, 18. Bosentan, which has potential hepatotoxicity, has been used in patients with cirrhosis without worsening of liver disease; however, the number of patients in these reports may be too low to detect this complication 19, 20.…”

Section: Discussionmentioning

confidence: 99%

AASLD 2006 distinguished service award to Allan W. Wolkoff

Cohen

2006

Hepatology

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PDE-5 inhibitors lower portal and pulmonary pressure in portopulmonary hypertension

Cited by 15 publications

References 7 publications

Treatment Barriers in Portopulmonary Hypertension

Treatment Barriers in Portopulmonary Hypertension

Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver

AASLD 2006 distinguished service award to Allan W. Wolkoff

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