Document Detail

Anthrax lethal and edema toxins produce different patterns of cardiovascular and renal dysfunction and synergistically decrease survival in canines.
MedLine Citation:
PMID:  21067373     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: High mortality in the 2001 US and recent European anthrax outbreaks suggests that better understanding of the effects of the toxins produced by this bacterium is needed to improve treatment.
METHODS AND RESULTS: Here, 24-h edema (ETx) and lethal (LeTx) toxin infusions were investigated for 96 hin sedated canines receiving mechanical ventilation. The initial study compared similarly lethal doses of ETx (n=8) or LeTx (n=15) alone. ETx was 24 times less lethal than LeTx, and the median time to death in nonsurvivors (n=6 and n=9, respectively) was shorter with ETx (42 vs 67 h; P=.04). Compared with controls(n=9), both toxins decreased arterial and central venous pressures and systemic vascular resistance and increased heart rate, cardiac index, blood urea nitrogen (BUN) level, creatinine (Cr) concentration, BUN:Cr ratio, and hepatic transaminase levels (P ≤ .05 for toxin effect or time interaction). However, ETx stimulated early diuresis,reduced serum sodium levels, and had more pronounced vasodilatory effects, compared with LeTx, as reflected by greater or earlier central venous pressures, systemic vascular resistance, and changes in the BUN:Cr ratio(P ≤ .01). LeTx progressively decreased the left ventricular ejection fraction (P ≤ .002). In a subsequent study, a lethal dose of LeTx with an equimolar nonlethal ETx dose (n=8) increased mortality, compared with LeTx alone (n=8; P= .05).
CONCLUSION: Shock with ETx or LeTx may require differing supportive therapies, whereas toxin antagonists should likely target both toxins.
Daniel A Sweeney; Xizhong Cui; Steven B Solomon; David A Vitberg; Thi S Migone; Dara Scher; Robert L Danner; Charles Natanson; G Mani Subramanian; Peter Q Eichacker
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2010-11-10
Journal Detail:
Title:  The Journal of infectious diseases     Volume:  202     ISSN:  1537-6613     ISO Abbreviation:  J. Infect. Dis.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-18     Completed Date:  2010-12-13     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0413675     Medline TA:  J Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1885-96     Citation Subset:  AIM; IM    
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
Antigens, Bacterial / toxicity*
Bacterial Toxins / toxicity*
Blood Pressure / drug effects
Cardiovascular System / drug effects*
Creatinine / blood
Disease Models, Animal
Heart Rate / drug effects
Kidney / drug effects*
Poisoning / pathology*,  physiopathology*
Survival Analysis*
Transaminases / blood
Urea / blood
Vascular Resistance / drug effects
Grant Support
Z01 CL008090-02/CL/CLC NIH HHS
Reg. No./Substance:
0/Antigens, Bacterial; 0/Bacterial Toxins; 0/anthrax toxin; 57-13-6/Urea; 60-27-5/Creatinine; EC 2.6.1.-/Transaminases

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