Antenatal Phosphodiesterase 4 Inhibition Restores Postnatal Growth and Pulmonary Development in a Model of Chorioamnionitis in Rabbits
| Autor: | Céline Méhats, Nicolas Joram, L. Homer, J. Caillon, B. Branger, J.-C. Roze, T. Moyon, Pierre-Henri Jarreau, Christèle Gras-Leguen, G. Potel, Elise Launay, Cédric Jacqueline |
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| Přispěvatelé: | Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes (UN), Université Paris Descartes - Paris 5 (UPD5), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), U767, Institut National de la Santé et de la Recherche Médicale (INSERM), ProdInra, Migration, Physiopathologie des Adaptations Nutritionnelles (PhAN) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_treatment
[SDV]Life Sciences [q-bio] PDE4 INHIBITORS Chorioamnionitis Weight Gain 0302 clinical medicine Pregnancy Saline Lung 0303 health sciences medicine.diagnostic_test INTRAAMNIOTIC ENDOTOXIN CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES Pathophysiology 3. Good health [SDV] Life Sciences [q-bio] Molecular Medicine Female Rabbits medicine.symptom Lung Volume Measurements medicine.drug medicine.medical_specialty Birth weight Context (language use) Inflammation ROLIPRAM Biology MATURATION RATS 03 medical and health sciences ALVEOLARISATION Internal medicine medicine Animals Rolipram 030304 developmental biology Pharmacology BRONCHOPULMONARY DYSPLASIA medicine.disease Elastic Tissue HYPEROXIA Disease Models Animal Bronchoalveolar lavage Endocrinology 030228 respiratory system CHRONIC LUNG-DISEASE Immunology Phosphodiesterase 4 Inhibitors |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics Journal of Pharmacology and Experimental Therapeutics, American Society for Pharmacology and Experimental Therapeutics, 2012, 340 (3), pp.620-628. ⟨10.1124/jpet.111.179085⟩ |
| ISSN: | 0022-3565 1521-0103 |
| Popis: | International audience; Chorioamnionitis is implicated in the pathophysiology of bronchopulmonary disease, and the associated inflammatory response is responsible for adverse effects on alveolar development. The aim of this work was to analyze the effects of a phosphodiesterase 4 (PDE4)-selective inhibitor, rolipram (a modulator of the inflammatory response), in an experimental model of chorioamnionitis on pulmonary development and on the processes of infection and inflammation. Rabbit mothers were assigned to four groups: 1) saline serum inoculation (controls); 2) Escherichia coli intrauterine inoculation (C+); 3) rolipram infusion (R+); and 4) E. coli inoculation + rolipram infusion (C+R+). High rates of morbility and mortality were noticed in mothers and pups (5 of 13 pregnant rabbits in groups with rolipram). Alveolar development, inflammation, and infection were analyzed in pups at day 0 and day 5. At day 0, in the context of chorioamnionitis, rolipram significantly decreased birth weight (p < 0.01) relative to that of controls (p < 0.05). At day 5, weight normalized in group C+R+ but not in group C+ relative to controls (p < 0.001); moreover, alveolar airspace volume was preserved in group C+R+ but not in group C+ (p < 0.05). Interstitial volume decreased in group C+ versus controls (p < 0.05) but was preserved in group C+R+. Specific alveolar area was not significantly modified by rolipram. No significant difference was found concerning bronchoalveolar lavage cellularity, and all blood cultures remained sterile. In this model of impaired alveologenesis, rolipram significantly preserved specific alveolar density. However, PDE4 inhibition induced antenatal fetal demise and growth retardation. |
| Databáze: | OpenAIRE |
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