Hemodynamic and Autonomic Effects of Intravenous Saterinone in Patients with Chronic Heart Failure

Abstract

In this study, the hemodynamic and neurohumoral/autonomic effects of intravenous saterinone (a selective phosphodiesterase type III inhibitor, with additional alpha 1-blocking properties) were evaluated. In a double-blind, placebo-controlled design, 36 patients with moderate to severe heart failure were studied (saterinone, n = 24; placebo, n = 12). Invasive hemodynamic measurements, by using right-heart catheterization, were performed, as well as measurement of plasma neurohormones and analysis of heart rate variability (HRV), to study drug influences on neurohumoral activation and autonomic tone. Systemic vascular resistance significantly decreased during saterinone infusion, accompanied by a decrease in systemic blood pressure (both p values < 0.05) and an increase in heart rate (p = 0.05). Filling pressures also decreased during saterinone, but this was statistically significant only for pulmonary capillary wedge pressure, whereas the cardiac index remained unaffected. Plasma neurohormones (norepinephrine, epinephrine, and renin activity) were not significantly influenced by saterinone. HRV analysis revealed no significant effect of saterinone on autonomic tone. These results suggest that intravenous saterinone has a significant vasodilating effect in patients with moderate to severe chronic heart failure (CHF), without exerting an adverse effect on the autonomic nervous system, as demonstrated by assessment of plasma neurohormones and HRV analysis.

Saterinone, a Phosphodiesterase (PDE) III Inhibitor and α1‐Adrenergic Antagonist

“…However, in healthy volunteers, saterinone significantly increased the left ventricular ejection fraction (6) and, in four studies with heart failure patients, saterinone produced an impressive increase in the cardiac index (4,10,22,23). Only in the fifth study did the cardiac index not change significantly after saterinone (18). Even though this is the only study with no relevant increase in the cardiac index, this finding is important because this was the only doubleblind and placebo-controlled trial.…”

“…The cardiac index did not change significantly. Plasma norepinephrine and epinephrine levels as well as plasma renin activity remained unchanged (18). In 12 patients with idiopathic congestive cardiomyopathy (NYHA III), the hemodynamic effects of saterinone were compared with those of dobutamine and sodium nitroprusside (NPN).…”

Low-level inotropic stimulation with type III phosphodiesterase inhibitors in patients with advanced symptomatic chronic heart failure receiving β-blocking agents

“…In addition, at low doses PDEIs have a neutral effect on heart rate variability, a measure of autonomic balance. They do not promote sympathetic dominance as do β-adrenergic receptor agonists [65,66].…”