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This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/L1193    most recent 00405.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Larrue, B. Articles by Storme, L. Search for Related Content PubMed PubMed Citation Articles by Larrue, B. Articles by Storme, L.

Pulmonary vascular effects of sildenafil on the development of chronic pulmonary hypertension in the ovine fetus

¹Department of Cardiothoracic Surgery, ²EA1049, Department of Biophysics, and ³Department of Pathology, Centre Hospitalier Régional Universitaire de Lille, Lille, France; ⁴Center for Surgical Technologies, Leuven, Belgium; ⁵Pfizer Laboratories, Sandwich, United Kingdom; and ⁶Department of Perinatology, Centre Hospitalier Régional Universitaire de Lille, Lille, France

Submitted 2 November 2004 ; accepted in final form 27 January 2005

We investigated the pulmonary vascular effects of prophylactic use of sildenafil, a specific phosphodiesterase-5 inhibitor, in late-gestation fetal lambs with chronic pulmonary hypertension. Fetal lambs were operated on at 129 ± 1 days gestation (term = 147 days). Ductus arteriosus (DA) was compressed for 8 days to cause chronic pulmonary hypertension. Fetuses were treated with sildenafil (24 mg/day) or saline. Pulmonary vascular responses to increase in shear stress and in fetal Pa_O2 were studied at, respectively, day 4 and 6. Percent wall thickness of small pulmonary arteries (%WT) and the right ventricle-to-left ventricle plus septum ratio (RVH) were measured after completion of the study. In the control group, DA compression increased PA pressure (48 ± 5 to 72 ± 8 mmHg, P < 0.01) and pulmonary vascular resistance (PVR) (0.62 ± 0.08 to 1.15 ± 0.11 mmHg·ml^–1·min^–1, P < 0.05). Similar increase in PAP was observed in the sildenafil group, but PVR did not change significantly (0.54 ± 0.06 to 0.64 ± 0.09 mmHg·ml^–1·min^–1). Acute DA compression, after brief decompression, elevated PVR 25% in controls and decreased PVR 35% in the sildenafil group. Increased fetal Pa_O2 did not change PVR in controls but decreased PVR 60% in the sildenafil group. %WT and RVH were not different between groups. Prophylactic sildenafil treatment prevents the rise in pulmonary vascular tone and altered vasoreactivity caused by DA compression in fetal lambs. These results support the hypothesis that elevated PDE5 activity is involved in the consequences of chronic pulmonary hypertension in the perinatal lung.

phosphodiesterase; pulmonary hypertension; nitric oxide; shear stress; vascular reactivity