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

Larrue, B., Jaillard, S., Lorthioir, M., Roubliova, X., Butrous, Ghazwan S., Rakza, T., Warembourg, H., Storme, L. (2005) Pulmonary vascular effects of sildenafil on the development of chronic pulmonary hypertension in the ovine fetus. American Journal of Physiology - Lung Cellular and Molecular Physiology, 288 (6). L1193-L1200. ISSN 1040-0605. (doi:10.1152/ajplung.00405.2004) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:12177)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/10.1152/ajplung.00405.2004

Abstract

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 ñ 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 ñ 5 to 72 ñ 8 mmHg, P < 0.01) and pulmonary vascular resistance (PVR) (0.62 ñ 0.08 to 1.15 ñ 0.11 mmHgúml-1úmin-1, P < 0.05). Similar increase in PAP was observed in the sildenafil group, but PVR did not change significantly (0.54 ñ 0.06 to 0.64 ñ 0.09 mmHgúml-1úmin-1). Acute DA compression, after brief decompression, elevated PVR 25% in controls and decreased PVR 35% in the sildenafil group. Increased fetal PaO2 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.

Item Type: Article
DOI/Identification number: 10.1152/ajplung.00405.2004
Subjects: R Medicine > R Medicine (General)
Divisions: Divisions > Division for the Study of Law, Society and Social Justice > School of Social Policy, Sociology and Social Research
Depositing User: M.P. Stone
Date Deposited: 09 Sep 2008 20:36 UTC
Last Modified: 16 Nov 2021 09:50 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/12177 (The current URI for this page, for reference purposes)

University of Kent Author Information

Butrous, Ghazwan S..

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