Toxicity of digoxin in acutely and chronically heat-exposed rats

Rats exposed acutely or chronically to high ambient temperatures (35 degrees C) were much more susceptible to digoxin toxicity than rats kept at 22 degrees C. LD 50 values were 8.8 +/- 1.8 mg/kg in the acute group and 10 +/- 5 2.5 mg/kg in the chronic group, which contrasted with 32.0 +/- 4.4 mg/kg in the control group. Toxic doses of digoxin cause marked hyperthermia in both the acute and chronic groups. Transferring the rats to 22 degrees C not only prevented the extreme hyperthermia, but also prevented death in the acute group (from the expected 100% to 0% mortality) and lowered the incidence of death in the chronic group (from the expected 78.5% to 30.7%). The suggestion is made that death may result from hyperthermia in the heat-exposed rats.