Bacillus anthracisEdema and Lethal Toxin Have Different Hemodynamic Effects but Function Together to Worsen Shock and Outcome in a Rat Model

Abstract

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. 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. 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.