Canine-effective plasma concentrations of antiarrhythmic drugs on the two-stage coronary ligation arrhythmia.

Seven drugs were tested for their antiarrhythmic effects on ventricular arrhythmias 24 and 48 hr after two-stage coronary ligation in conscious beagles. Venous blood samples were drawn for plasma drug assays. Minimum effective plasma concentrations of drugs were calculated from derived concentration-time curves. Effective drugs and their minimum effective concentrations for the suppression of arrhythmias 24 and 48 hr after coronary ligation were: disopyramide, 4.2 and 2.3 micrograms/ml; procainamide, 26.4 and 27.0 micrograms/ml; phenytoin, 8.4 and 6.4 micrograms/ml; and a new beta-blocker, N-696, 7.6 and 8.7 micrograms/ml. The concentrations of disopyramide and phenytoin were almost the same as those reported for human antiarrhythmic concentrations, but those of procainamide were higher than those reported for man. Lidocaine, verapamil and a new beta-blocker, OPC-1427, were ineffective. Membrane-stabilizing effects seem to be important in suppressing the canine two-stage coronary ligation arrhythmia.