Toxicity of digoxin in acutely and chronically heat-exposed rats

Rats exposed acutely or chronically to high ambient temperatures (35°C) were much more susceptible to digoxin toxicity than rats kept at 22°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°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.