Acute Hemodynamic Effects of SIN-1 vs. Isosorbide Dinitrate

Summary: The effects of intravenous SIN-1 (1 mg) and sublingual isosorbide dinitrate (ISDN) (5 mg) were studied in 12 patients with stable left ventricular failure (NYHA class III-IV) secondary to ischemic, hypertensive, or idiopathic dilated cardiomyopathy. Data were collected during two periods separated by a washout phase, in a randomized, crossover, double-blind and double-placebo design. Heart rate was modified neither by SIN-1 nor by ISDN. A nonsignificant increase in cardiac output and decrease in aortic pressure were observed with both drugs. A patent reduction (>15% from baseline value) in mean pulmonary wedge pressure, pulmonary artery pressures, and mean right atrial pressure was observed in 7 patients after ISDN and in 10 after SIN-1. The mean maximal pressure decrease tended to be greater after SIN-1 than after ISDN, but without statistical significance. A trend for a shorter delay to effect and for a prolonged action after SIN-1 than after ISDN was also observed. The relationship between the pharmacodynamics and the pharmacokinetics of SIN-1 suggested the action of a derived metabolite. No side effects occurred. Thus, in stable left ventricular failure, intravenous SIN-1 and sublingual ISDN have similar acute hemodynamic effects, suggesting a predominant venodilation. SIN-1 is safe, seems more frequently active than ISDN, and its effects tend to be more rapid and more sustained.