Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs.
Crit Care Med
; 45(12): e1240-e1246, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-28953499
ABSTRACT
OBJECTIVES:
To determine the feasibility of using a cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmaceuticals, Boston, MA), as a therapeutic strategy for treating pulmonary edema.DESIGN:
Prospective laboratory animal investigation.SETTING:
Animal research laboratory.SUBJECTS:
Newborn and 3 days to 1 week old pigs.INTERVENTIONS:
Hydrostatic pulmonary edema was induced in pigs by acute volume overload. Ivacaftor was nebulized into the lung immediately after volume overload. Grams of water per grams of dry lung tissue were determined in the lungs harvested 1 hour after volume overload. MEASUREMENTS AND MAINRESULTS:
Ivacaftor significantly improved alveolar liquid clearance in isolated pig lung lobes ex vivo and reduced edema in a volume overload in vivo pig model of hydrostatic pulmonary edema. To model hydrostatic pressure-induced edema in vitro, we developed a method of applied pressure to the basolateral surface of alveolar epithelia. Elevated hydrostatic pressure resulted in decreased cystic fibrosis transmembrane conductance regulator activity and liquid absorption, an effect which was partially reversed by cystic fibrosis transmembrane conductance regulator potentiation with ivacaftor.CONCLUSIONS:
Cystic fibrosis transmembrane conductance regulator potentiation by ivacaftor is a novel therapeutic approach for pulmonary edema.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Edema Pulmonar
/
Quinolonas
/
Regulador de Condutância Transmembrana em Fibrose Cística
/
Agonistas dos Canais de Cloreto
/
Aminofenóis
Tipo de estudo:
Observational_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article