Pulmonary vascular effects of sildenafil on the development of chronic pulmonary hypertension in the ovine fetus
| Autor: | B. Larrue, S Jaillard, Laurent Storme, H. Warembourg, Ghazwan Butrous, T. Rakza, X. Roubliova, M. Lorthioir |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Pulmonary Circulation Physiology Sildenafil Phosphodiesterase Inhibitors Hypertension Pulmonary Pulmonary Artery Piperazines Sildenafil Citrate chemistry.chemical_compound Fetus 3' 5'-Cyclic-GMP Phosphodiesterases Physiology (medical) Ductus arteriosus Internal medicine medicine.artery medicine Animals Sulfones Lung Sheep business.industry Respiratory disease Hemodynamics Cell Biology Ductus Arteriosus medicine.disease Pulmonary hypertension Oxygen Vasodilation Endocrinology medicine.anatomical_structure chemistry Purines Pulmonary artery Chronic Disease Vascular resistance Cardiology Vascular Resistance Stress Mechanical business |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 288(6) |
| ISSN: | 1040-0605 |
| Popis: | 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 PaO2were 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 PaO2did 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. |
| Databáze: | OpenAIRE |
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