TY - JOUR
T1 - Involvement of the Bufadienolides in the Detection and Therapy of the Acute Respiratory Distress Syndrome
AU - Abbas, Mir M.K.
AU - Patel, B.
AU - Chen, Q.
AU - Jiang, W.
AU - Moorthy, B.
AU - Barrios, Roberto
AU - Puschett, J. B.
N1 - Funding Information:
These studies were supported by the Texas A&M University College of Veterinary Medicine and Biosciences, College Station, Texas and the Jules B. Puschett Research Endowment Fund, Houston, Texas. All the authors take responsibility for the accuracy of the data presented in this manuscript: All of them have read the manuscript prior to submission for publication. Mr. Abbas and Dr. Puschett wrote the majority of the paper which was approved by the other co-authors.
Publisher Copyright:
© 2017, Springer Science+Business Media New York.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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.
AB - 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.
KW - ARDS
KW - Hyperoxia
KW - Marinobufagenin
KW - Resibufogenin
KW - Acute Respiratory Distress Syndrom
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U2 - 10.1007/s00408-017-9989-1
DO - 10.1007/s00408-017-9989-1
M3 - Article
C2 - 28260175
AN - SCOPUS:85020647793
SN - 0341-2040
VL - 195
SP - 323
EP - 332
JO - Lung
JF - Lung
IS - 3
ER -