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Involvement of the Bufadienolides in the Detection and Therapy of the Acute Respiratory Distress Syndrome

Authors :
Weiwu Jiang
Roberto Barrios
Q. Chen
B. Patel
Bhagavatula Moorthy
Jules B. Puschett
Mir M.K. Abbas
Source :
Lung. 195:323-332
Publication Year :
2017
Publisher :
Springer Science and Business Media LLC, 2017.

Abstract

The acute respiratory distress syndrome (ARDS) represents a major challenge for clinicians as well as basic scientists. The mortality rate for ARDS has been maintained within the range of 40-52%. The authors have examined the involvement of the "cardiotonic steroids" in the pathogenesis and therapy of ARDS. We have studied the possible role of the bufadienolide, marinobufagenin (MBG), in the pathogenesis of ARDS in both a rat model of ARDS and in patients afflicted with that disorder. In addition, the potential therapeutic benefit of an antagonist of MBG, resibufogenin (RBG), in an animal model has been evaluated.A syndrome resembling human ARDS was produced in the rat by exposing the animals to 100% oxygen for 48 h. In other animals, RBG was administered to these "hyperoxic" rats, and the serum MBG was measured. In human ICU patients, urinary samples were examined for levels of MBG, and the values were compared to those obtained from other ICU patients admitted with diagnoses other than ARDS.(1) Exposure of rats to hyperoxia produced a histologic picture which resembled that of human ARDS. (2) Serum levels of MBG in the "hyperoxic" rats substantially exceeded those obtained in animals exposed to ambient oxygen levels and were reduced to normal by RBG. (3) In ARDS patients, substantial elevations in urinary MBG were obtained compared to those in non-ARDS ICU patients.MBG may serve as an important biomarker for the development of ARDS, and RBG may represent a preventative/therapy in this disorder.

Details

ISSN :
14321750 and 03412040
Volume :
195
Database :
OpenAIRE
Journal :
Lung
Accession number :
edsair.doi.dedup.....86d1e5fa768921a68fa946de3fff0669
Full Text :
https://doi.org/10.1007/s00408-017-9989-1