Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs
Year: 2017
Type: article
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 MAIN RESULTS: 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.
Source: Critical Care Medicine
Institution: University of Iowa
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Gene Therapy For Cystic Fibrosis Lung Disease, Multidisciplinary Lung Research Career Development Program, Origins of Cystic Fibrosis Airway Disease, The University of Iowa Clinical and Translational Science Award, Environmental Health Sciences Research Center, Precision Medicine Center for Cystic Fibrosis
OpenAlex ID: W2756486990