Acute Neurohormonal and Hemodynamic Response to a New Peak III Phosphodiesterase Inhibitor (ICI 153,110) in Patients with Chronic Heart Failure

Abstract

Peak III phosphodiesterase (PDE) inhibitors have combined positive inotropic and vasodilator effects. We studied 10 patients with chronic heart failure during and after infusion of intravenous (i.v.) ICI 153,110, an investigational peak III PDE inhibitor. Maximum hemodynamic response for the group occurred after cessation of infusion at a lower plasma drug concentration. At maximum hemodynamic response, cardiac index (CI) increased (2.4 ± 0.5 vs. 3.2 ± 0.37 L/min/m², p < 0.05) with a decrease in mean arterial pressure (MAP 91 ± 5 vs. 80 ± 3 mm Hg, p < 0.05), pulmonary capillary wedge pressure (PCWP 25 ± 2 vs. 17 ± 3.1 mm Hg, p < 0.01), systemic vascular resistance (SVR 1,422 ± 106 vs. 983 ± 97 dynes ± s ± cm⁻⁵, p < 0.05) and pulmonary vascular resistance (PVR 227 ± 39 vs. 16 ± 31 dynes ± s ± cm⁻⁵, p < 0.05). During the infusion, plasma renin activity (PRA) decreased from 6.34 ± 2.53 to 3.6 ± 3 ng/ml/h (NS). The five patients with high baseline PRA had a significant decrease (11.2 ± 2.5 vs. 5.4 ± 1.67 ng/ml/h, p < 0.01) that preceded changes in CI and SVR by 1–2 h. These data suggest that reduction in PRA may have contributed to the hemodynamic effects of this peak III PDE inhibitor.