Canine Model Investigating Cardiopulmonary Effects B. anthracis Edema and Lethal

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In the present study, a canine model has been developed to study the cardiopulmonary effects of ETx and LeTx alone and together. This model utilizes continuously sedated and mechanically ventilated animals that have both systemic and pulmonary arterial catheters in place. Intravascular hemodynamic studies are complemented by serial echocardiographic measures. In studies thus far, the effects of individual toxins administered as 24 h infusions have been tested. In these studies, ETx and LeTx have shown to produce very different patterns of cardiovascular injury. ETx produces marked decreases in preload, tachycardia and hypotension that occurs early and persists for up to 96 h. LeTx on the other hand produces gradual hypotension and progressive decreases in left ventricular function. Thus ETx appears to have profound effects on the peripheral vasculature while LeTx is having direct myocardial depressant effects. These studies are ongoing and will shortly assess the effects of the two toxins together. Findings to date emphasize how important adjunctive treatments may be that directly target the two toxins during anthrax associated shock.