Journal article
Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs
Critical care medicine, Vol.45(12), pp.e1240-e1246
12/2017
DOI: 10.1097/CCM.0000000000002720
PMCID: PMC5693779
PMID: 28953499
Abstract
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.
Prospective laboratory animal investigation.
Animal research laboratory.
Newborn and 3 days to 1 week old pigs.
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.
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.
Cystic fibrosis transmembrane conductance regulator potentiation by ivacaftor is a novel therapeutic approach for pulmonary edema.
Details
- Title: Subtitle
- Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs
- Creators
- Xiaopeng Li - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IALuis G Vargas Buonfiglio - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IARyan J Adam - Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IADavid A Stoltz - Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IAJoseph Zabner - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IAAlejandro P Comellas - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Critical care medicine, Vol.45(12), pp.e1240-e1246
- DOI
- 10.1097/CCM.0000000000002720
- PMID
- 28953499
- PMCID
- PMC5693779
- NLM abbreviation
- Crit Care Med
- ISSN
- 0090-3493
- eISSN
- 1530-0293
- Publisher
- United States
- Grant note
- P30 ES005605 / NIEHS NIH HHS P01 HL091842 / NHLBI NIH HHS P01 HL051670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS T32 HL007638 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
- Record Identifier
- 9984025440902771
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