Cardiovascular effects of aprindine, a new antiarrhythmic drug

The effects of aprinidine (AC 1802), a new antiarrhythmic drug, were studied in 9 anesthetized pigs. Aprindine was administered intravenously in cumulative doses until serum levels larger than or equal to 8 mug/ml were obtained, which is more than three times the therapeutic level in man (+/- 2.5 mug/ml). Doses less than 1.75 mg/kg (serum levels 3.4 mug/ml) had no effect on the pump function of the heart, as preload, afterload, and the contractile state of the heart were not significantly altered. However, at these levels, electrocardiographic changes were significant as QRS increased to 132 +/- 14% of control (P less than 0.005). At the highest serum levels (8.7 mug/ml), cardiac output had decreased to 78 +/- 15% of control. This appears to be the result of negative inotropic properties of the drug, as preload remained unchanged and afterload actually decreased. Most striking at these levels were the electrocardiographic changes, as P-Q length increased to 281 +/- 93% of control and QRS width to 341 +/- 85%. The changes in the width of the QRS complex, prove to be the earliest indicator of aprindine activity and may serve as a warning of intoxication.