Bacillus anthracis infections are frequently associated with severe and often irreversible hypotensive
shock despite appropriate
antibiotics and aggressive hemodynamic and pulmonary support. Based on the observations that the
anthrax secreted
proteins-protective
antigen (PA), lethal factor (LF), and
edema factor (EF) also produce
shock and mortality in animal models, we chose to characterize further the clinical chemistries and microscopic pathology of toxin treated rats. Groups of three male Sprague Dawley rats received bolus
intravenous infusions of PA/LF, PA/EF, LF, or EF alone and blood samples and tissues were collected and assayed for chemistries and tissue pathology. In PA/LF and PA/EF treated animals but not other groups, chemistries showed transaminasemia and elevated
lactate dehydrogenase. PA/LF treated animals alone showed elevated
hemoglobin and hematocrits; PA/EF treated animals alone showed
lymphopenia. Pathology was remarkable for
pulmonary edema in PA/LF treated rat lungs and pulmonary
hemorrhage in PA/EF treated rat lungs. These results are consistent with our and others' previous findings that the morbidity and mortality associated with
anthrax are not
cytokine-mediated but due to a direct effect of the toxins on the cardiovascular system along with toxin-specific alterations in blood counts. PA/LF pathology matches that seen with acute
cardiac failure, and PA/EF pathology coincides with direct vascular endothelial injury. These observations provide a rational basis for
drug interventions to reduce the effect of these toxins on the heart and blood vessels.