Facilitation of lethal ventricular arrhythmias by therapeutic digoxin in conscious post infarction dogs.

The proarrhythmic potential of digoxin, administered in a therapeutic dosage regimen, was evaluated in conscious dogs in the subacute phase of myocardial infarction. In this evaluation, digoxin (0.0125 mg/kg/day intravenously) or vehicle were administered to conscious dogs for periods of 5 to 7 days, commencing 4 to 5 days after anterior myocardial infarction. Before treatment, programmed ventricular stimulation failed to initiate ventricular tachycardia in 26 post infarction dogs. After treatment, programmed stimulation initiated ventricular tachyarrhythmias in only 1 of 13 digoxin-treated dogs (1.36 +/- 0.17 ng/ml serum digoxin) and in 0 of 13 vehicle-treated dogs. However, the incidences of early ventricular fibrilation (4 of 10 digoxin vs 0 of 12 vehicle; p less than 0.05) and of 24-hour mortality (6 of 10 digoxin vs 2 of 12 vehicle; p less than 0.05) occurring in response to the development of posterolateral ischemia in the presence of previous anterior myocardial infarction was significantly greater in digoxin-treated (1.47 +/- 0.19 ng/ml serum digoxin) than in vehicle-treated animals. These findings suggest an enhanced susceptibility toward the development of ischemia-related lethal arrhythmias in the presence of therapeutic digoxin serum concentrations early after myocardial infarction, which is not predicted by programmed ventricular stimulation testing.