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04.03.2017 | Acute Lung Injury

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

verfasst von: Mir M. K. Abbas, B. Patel, Q. Chen, W. Jiang, B. Moorthy, R. Barrios, J. B. Puschett

Erschienen in: Lung | Ausgabe 3/2017

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Abstract

Purpose

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.

Method

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.

Results

(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.

Conclusions

MBG may serve as an important biomarker for the development of ARDS, and RBG may represent a preventative/therapy in this disorder.

A life threatening disorder characterized by severe hypoxemia, dyspnea, and bilateral pulmonary opacities in radiographic and computed tomographic (CT) scans.

An endogenous bufadienolide that regulates the ubiquitous Na⁺/K⁺ ATPase enzyme and is implicated in states characterized by volume expansion and increased vascular permeability.

A pregnancy-specific disorder characterized by high blood pressure and proteinuria.

A bufadienolide that is an antagonist of MBG and it is shown to prevent all of the manifestations of preeclampsia in a rat model.

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Titel: Involvement of the Bufadienolides in the Detection and Therapy of the Acute Respiratory Distress Syndrome
verfasst von: Mir M. K. Abbas
B. Patel
Q. Chen
W. Jiang
B. Moorthy
R. Barrios
J. B. Puschett
Publikationsdatum: 04.03.2017
Verlag: Springer US
Erschienen in: Lung / Ausgabe 3/2017
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI: https://doi.org/10.1007/s00408-017-9989-1

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