Hemodynamics, Tolerability, and Pharmacokinetics of Linsidomine (SIN-1) Infusion During the Acute Phase of Uncomplicated Myocardial Infarction

To determine a dose regimen and evaluate the hemodynamic effects of linsidomine administered by continuous intravenous (i.v.) infusion, 10 patients were studied during the acute phase of uncomplicated myocardial infarction (MI). Systolic, diastolic, and mean (SBP, DBP, MBP) systemic blood pressure and heart rate (HR) were measured noninvasively. Pulmonary artery pressures were monitored after insertion of a Swan-Ganz catheter, which also enabled measurement of cardiac output (CO) and cardiac index (CI) by thermodilution. After baseline hemodynamic values (period A) were determined, linsidomine (SIN-1) was infused at a rate of 0.8 mg/h and subsequently adjusted to obtain a 10% decrease in MBP from its baseline value (period B). The infusion was then continued for 3 h at a constant rate (period C), and pressures were monitored for 1 h after the infusion was discontinued (period D). There were no significant changes in systemic or pulmonary arterial pressures or in HR between period B and period C. In contrast, CI decreased moderately (p < 0.05), with no clinical consequences. Return to baseline hemodynamics was obtained at the end of period D. Our findings indicate that continuous i.v. administration of SIN-1 (at a mean flow rate of 1 mg/h) is well tolerated and appears to be suitable for use in acute coronary syndromes.