Sildenafil And Hypoxic Pulmonary Hypertension

BAKTYBEK K. KOJONAZAROV1, MIRSAID M. MIRRAKHIMOV2, NICHOLAS W. MORRELL3, MARTIN R. WILKINS4, ALMAZ A. ALDASHEV1

1 Institute of Molecular Biology and Medicine, Bishkek, Kyrgyzstan

2 National centre of Cardiology and Internal Medicine, Bishkek, Kyrgyzstan

3 Cambridge University, Cambridge, United Kingdom

4 Imperial College of Medicine, London, United Kingdom

Abstract: We have previously demonstrated that sildenafil inhibits hypoxia-induced pulmonary vasoconstriction in healthy subjects. The aim of this study was to investigate the effects of the PDE5 inhibitor sildena-fil on pulmonary hemodynamics in patients with high altitude pulmonary hypertension (HAPH). Twenty-two patients with HAPH were randomized by age and level of mean pulmonary arterial pressure (PAP) in 3 groups: a first group (n=9) treated with 25 mg of sildenafil 3 times a day; a second group (n=5) - received 100 mg of sildenafil 3 times a day; a third group (n=8) - treated with placebo. Pulmonary hemodynamics was measured by right heart catheterization at baseline and after 12 weeks of sildenafil therapy at, before and 1 hour after taking sildenafil or placebo.

In the first group the mean PAP decreased after 12 weeks of sildenafil treatment from 36 ± 8 to 30 ± 8 mm Hg and to 25 ± 7 mm Hg (p <0.007) 1 hour after 25 mg of sildenafil, in the second group, mean PAP decreased after 12 weeks from 32 ± 3 to 26 ± 3 mm Hg (p <0.01) and to 21 ± 2 mm Hg (P <0.001) 1 hour after 100 mg of sildenafil, in the third group the mean PAP did not significantly change. Both doses improved the 6-minute walk distance, in the first group of patients by 45.4 m (p <0.01) and in the second group by 40.0 m (p <0.049). No side effects were observed.

We conclude that sildenafil therapy decreases PAP and could be recommended for treatment of HAPH.

Keywords: altitude; pulmonary hypertension; sildenafil; exercise; right heart failure.

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