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Benefits of ethyl gallate versus norepinephrine in the treatment of cardiovascular collapse in Pseudomonas aeruginosa septic shock in dogs.
MedLine Citation:
PMID:  22020237     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
INTERVENTIONS:: Vasopressor therapy is required in septic shock to maintain tissue perfusion in the face of hypotension. Unfortunately, there are significant side effects of current vasopressors, and newer agents need to be developed. We recently discovered that ethyl gallate, a nonflavonoid phenolic antioxidant found in food substances, could reverse low mean arterial pressure found in an experimental model of septic shock due to inhibition of hydrogen peroxide signaling. In the present study, we compared the hemodynamic and biochemical effects of ethyl gallate vs. those of the commonly used vasopressor, norepinephrine, in a bacteremic canine model of Pseudomonas aeruginosa sepsis in two protocols. MEASUREMENTS AND MAIN RESULTS:: We performed these studies in anesthetized and mechanically ventilated dogs. In the early treatment protocol, we infused P. aeruginosa until mean arterial pressure first decreased to ∼60 mm Hg (about 2-3 hrs), after which we stopped the infusion and randomly administered ethyl gallate or norepinephrine in respective groups. In the late treatment protocol, we administered ethyl gallate or norepinephrine after a sustained ∼5-hr decrease in mean arterial pressure to 60 mm Hg and continued the infusion for the duration of the experiment. We followed parameters for over 10 hrs after the initiation of P. aeruginosa in both groups. We measured stroke work, urine output, serum creatinine, among other parameters, and used serum troponin T as an index of myocardial injury. We found that in both protocols, ethyl gallate and norepinephrine improved mean arterial pressure and stroke work to similar extents over the duration of the study. Particularly in the late treatment protocol, ethyl gallate resulted in a lower heart rate, a lower troponin T, and a greater urine output as compared with norepinephrine (p < .05). CONCLUSIONS:: These results suggest that phenolic antioxidants, such as ethyl gallate, that inhibit hydrogen peroxide signaling, may represent an alternative class of vasopressors for use in septic shock.
Authors:
Jose Gotes; Krika Kasian; Hans Jacobs; Zhao-Qin Cheng; Steven N Mink
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-20
Journal Detail:
Title:  Critical care medicine     Volume:  -     ISSN:  1530-0293     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
From the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (JG), Mexico; and the Departments of Medicine (KK, ZQC, SNM), Biochemistry and Medical Genetics (HJ), and Pharmacology and Therapeutics (SNM), University of Manitoba, Winnipeg, Manitoba, Canada.
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