title: Bacillus anthracis edema and lethal toxin have different hemodynamic effects but function together to worsen shock and outcome in a rat model.
abstract: BACKGROUND
  To better define the contribution of edema toxins (ETx) and lethal toxins (LeTx) to shock with Bacillus anthracis, recombinant preparations of each were investigated alone or together in rats.
  
  
  RESULTS
  Lethal dose ranges (0%-100% lethality) of ETx (200-800 microg/kg as a 24-h infusion) were higher than those of LeTx (12.5-200 microg/kg) (P<.0001). However, compared with LeTx, similarly lethal ETx doses produced earlier and greater reductions in mean blood pressure (MBP) and increased, rather than decreased, heart rate (HR) (P<.05 for all). Combining either similar weight or lethal doses of ETx and LeTx increased the hazard ratio for death (log +/- standard error) similar to the sum calculated with the toxin's effects alone (2.6+/-1.1 observed vs. 2.9+/-1.0 calculated for similar weight and 3.1+/-1.0 vs. 3.9+/-1.5 for similar lethal doses; P=.5 for both). Early (< or =10 h) and late during infusion, ETx and LeTx together also altered MBP and HR in patterns consistent with the sum of their individual effects.
  
  
  CONCLUSIONS
  ETx was approximately 10 times less lethal than LeTx but produced greater hypotension and added to the latter's harmful effects. These findings suggest that it may be appropriate for antitoxin therapies for B. anthracis to target both ETx and LeTx.
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Xizhong
authors.initials: X
authors.lastname: Cui
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.forename: Michael W
authors.initials: MW
authors.lastname: Laird
authors.forename: Mani
authors.initials: M
authors.lastname: Subramanian
authors.forename: Mahtab
authors.initials: M
authors.lastname: Moayeri
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Leppla
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Fitz
authors.forename: Junwu
authors.initials: J
authors.lastname: Su
authors.forename: Kevin
authors.initials: K
authors.lastname: Sherer
authors.forename: Peter Q
authors.initials: PQ
authors.lastname: Eichacker
mesh_terms: D000818:Animals; D000881:Anthrax / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*; D000942:Antigens, Bacterial / Q000633:toxicity*; D001408:Bacillus anthracis / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D001794:Blood Pressure; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006339:Heart Rate; D006454:Hemoglobins / Q000032:analysis; D007958:Leukocyte Count; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000633:toxicity; D012769:Shock / Q000382:microbiology*; D016019:Survival Analysis; D013997:Time Factors; D037521:Virulence Factors / Q000633:toxicity*
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D006454:Hemoglobins; D011994:Recombinant Proteins; D037521:Virulence Factors; C030325:anthrax toxin; D009569:Nitric Oxide