Anthrax toxins induce shock in rats by depressed cardiac ventricular function

Area of Science:

• Cardiovascular Physiology
• Toxicology
• Infectious Diseases

Background:

• Anthrax infections often lead to severe, irreversible hypotensive shock.
• Bacillus anthracis toxins induce hypotension through unknown, non-cytokine-mediated mechanisms.
• Anthrax toxins are suspected to have direct cardiovascular effects.

Purpose of the Study:

• To characterize the cardiovascular effects of anthrax lethal toxin (LeTx) and edema toxin (EdTx).
• To investigate the mechanisms underlying toxin-induced hypotension and shock.
• To provide a basis for designing interventions against anthrax toxicity.

Main Methods:

• Systemic administration of LeTx and EdTx to rats.
• Monitoring of blood pressure via telemetry.
• Echocardiography to assess cardiac function and dimensions.
• Measurement of serum protective antigen (PA) concentrations.

Main Results:

• Both LeTx and EdTx induced hypotension in rats.
• LeTx increased ventricular areas and propagation velocity, indicating impaired systolic function.
• EdTx increased heart rate, suggesting reduced preload.
• Toxins were readily taken up into tissues, with effects seen within hours.

Conclusions:

• LeTx and EdTx exert distinct cardiovascular effects, contributing to irreversible shock.
• LeTx reduces left ventricular systolic function, while EdTx affects preload.
• Understanding these mechanisms is crucial for developing effective anthrax treatments.