Effects of pilsicainide on systemic hemodynamics and cardiac function of anesthetized dogs

The effects of pilsicainide, propafenone and flecainide on systemic hemodynamics and cardiac function were compared in anesthetized open-chest dogs. Pilsicainide, propafenone and flecainide given intravenously at 1 and 3 mg/kg produced dose-dependent decreases in the mean aortic pressure. The heart rate was decreased by pilsicainide and flecainide, but not by propafenone. The three drugs increased the left ventricular end-diastolic pressure and reduced the first derivative of left ventricular pressure and myocardial oxygen consumption. Pilsicainide decreased aortic, vertebral, coronary and renal blood flows in a dose-dependent manner at 1 and 3 mg/kg. Propafenone increased aortic and vertebral blood flows at 1 mg/kg and decreased coronary and renal blood flows at 3 mg/kg. Flecainide did not significantly change blood flow, except for an increase in the aortic blood flow with 3 mg/kg. The total peripheral, vertebral, coronary and renal vascular resistances were increased by pilsicainide, but not by flecainide. Propafenone decreased total peripheral and vertebral vascular resistances, but hardly affected the coronary and renal vascular resistances. The stroke volume was decreased by 1 and 3 mg/kg pilsicainide in a dose-dependent manner, and increased by 1 and 3 mg/kg propafenone, but not significantly changed by 1 or 3 mg/kg flecainide. The stroke work index was decreased by 3 mg/kg pilsicainide and 3 mg/kg flecainide. The effects of pilsicainide correlated with the changes in its plasma concentration with time. The results indicate that pilsicainide has a negative inotropic activity similar to that of propafenone and flecainide. Pilsicainide and flecainide show almost the same effects with a slightly different efficacy, while propafenone exerts different effects upon some cardiovascular functions.