Hemodynamic effects of SIN-1 in acute left heart failure

Abstract

To assess the hemodynamic effects of SIN-1, the active metabolite of the venodilator molsidomine, after acute as well as chronic intravenous administration, ten patients with exacerbation of chronic heart failure were studied. After a mean bolus dose of 2 mg of SIN-1, mean right atrial pressure (MRAP), mean pulmonary artery pressure (MPAP), and pulmonary capillary wedge pressure (PCAP) decreased significantly up to the 60th minute; pulmonary vascular resistance (PVR) decreased significantly up to the 30th minute, while cardiac index (CI) and systemic vascular resistance (SVR) remained unchanged. During a 24-hour continuous infusion of SIN-1, MRAP, MPAP, and PCAP decreased significantly, while CI, PVR, and SVR remained largely unaltered. No dose adjustment was required to maintain the hemodynamic effects over 24 hours. The absence of noteworthy side effects and tolerance during this prolonged administration indicate that SIN-1 is a potentially useful drug in the management of patients admitted with exacerbation of heart failure.

Haemodynamic evaluation of two regimens of molsidomine in patients with chronic congestive heart failure

“…Haemodynamic effects identical to those demonstrated in the present study have been found with comparable dosage ferms of molsidomine and SIN-l, its major metabolite [22][23][24]. The present study, therefore, using different methods, has confirmed the sydnonimines as being substances which act predominantly on preload [22][23][24].…”

“…The present study, therefore, using different methods, has confirmed the sydnonimines as being substances which act predominantly on preload [22][23][24]. Nevertheless, there have been some reports [22][23][24][25] of decreases in total vascular resistance and, consequently, in after-load, as could also be seen from the tendency for such decreases to occur in the present study, and which was paralleled by increases in cardiac output taking place exclusively at the same points in time (Table 1). Consequently, since this points to a possibly dose dependent influence of molsidomine on all types of vascular resistance, administration of an even higher dose in sustained-release form would seem justified for effective treatment of chronic congestive heart failure, this should also affect left ventricular afterload, i.e.…”

“…Heart rate at rest was the only haemodynamic parameter which was not affected significantly by either of the regimens tested compared with the placebo or control groups, respectively, neither in the present study nor in other studies which have assessed the haemodynamic effects of sydnonimines [15,[22][23][24][25][26]. Altogether it can be assumed that changes in haemodynamic parameters brought about by molsidomine in the dosages tested do not lead to statistically significant changes in heart rate at rest, which, in turn, obviously is not augmented unless more marked reductions of systemic resistance and arterial blood pressure take place at higher dosages, e.g.…”

“…Consequently, since this points to a possibly dose dependent influence of molsidomine on all types of vascular resistance, administration of an even higher dose in sustained-release form would seem justified for effective treatment of chronic congestive heart failure, this should also affect left ventricular afterload, i.e. reduce systemic vascular resistance and enhance both cardiac output and stroke volume, respectively [22][23][24][25].…”

“…Mean arterial pressure (MAP) was calculated as diastolic plus one third of the pulse pressure. Systemic vascular resistance (SVR), pulmonary arteriolar resistance (PAR) and total pulmonary resistance (TPR) were expressed as dyn • s • cm -5 and calculated as SVR = 80 x (MAP RAP)/CO, PAR = 80 x (PAPmean -PAPdiastolic)/ CO and TPR = 80 x PAPmean/CO, respectively [21,22]. at 6 h after the second tablet, the change amounted to -3 % (NS).…”