Premium
Investigation of the Cardiotonic Steroids, Marinobufagenin and Resibufogenin, in the Acute Respiratory Distress Syndrome
Author(s) -
Abbas Mir Mohammad Kamran,
Chen Qingzheng,
Das Aayudh,
Oliver Joel,
Jiang Weiwu,
Moorthy Bhagavatula,
Patel Bela,
Morin Kristi,
Puschett Jules
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.982.4
Subject(s) - ards , medicine , sepsis , respiratory distress , pneumonia , respiratory system , endocrinology , physiology , gastroenterology , anesthesia , lung
The bufodienolides are a group of “cardiac glycosides” also termed the “cardiotonic steroids”, which are produced largely in the adrenal gland, but also in the placenta, as well as, perhaps, in the brain. They circulate in the blood and are excreted into the urine. They were originally discovered in the skin and the venom of the common toad (Bufo marinus), hence their appellation. Their major action is that of the inhibition of the ubiquitous enzyme, Na + /K + ATPase. Acute respiratory distress syndrome (ARDS) is a life‐threatening disorder with a prevalence rate of 64 cases per 100,000 person‐years and a mortality rate of 40–52%. It is most often encountered in severely ill patients with a background of sepsis, trauma, complicated severe pneumonia and burns. Aside from improvements in ventilator therapy, there have occurred no new therapeutic strategies that improve survival. In an animal model of ARDS involving the production of the disease by exposing the animals (rats) to > 95% oxygen for 48–60 hours, serum levels of marinobufagenin (MBG) rose to 99.7 +/− 17.5 (SE) pg/ml from those determined in sham rats (mean: 25.7 +/− 2.3 SE pg/ml) (p<0.02). One hour after the hyperoxia period was completed, the intraperitoneal administration of 160 ug of resibufagenin (RBG), an antagonist of MBG, in a third group of animals, resulted in a decline of mean serum MBG to 17.2 +/− 2.7 pg/ml (p< 0.001). The mean values for MBG of the sham and hyperoxia + RBG groups differed (p= 0.003). In 18 patients with ARDS, recruited from the ICU of the Memorial‐Hermann Hospital in Houston, TX, the mean urinary excretion level of MBG/mg creatinine was 760 +/− 233 pg/mg creatinine compared to that obtained in 19 control patients admitted to the ICU for other indications was 169 +/− 74 pg/mg creatinine (p= 0.01). We conclude that: 1) Elevated levels of MBG serve to diagnose ARDS and 2) RBG may prove to provide “rescue” therapy for this disorder. Support or Funding Information Jules B. Puschett, M.D. Research Endowment Fund