caa a22 4500 477072704 CHVBK 20180405111430.0 cr unu---uuuuu 170330e19961001xx s 000 0 eng 10.1007/BF00823591 doi (NATIONALLICENCE)springer-10.1007/BF00823591 Acute hemodynamic effects and preload-dependent cardiovascular profile of the partial phosphodiesterase inhibitor nanterinone in patients with mild to moderate heart failure [Elektronische Daten] [W. Remme, M. van der Ent, G. Bartels, D. van Schelven, D. van Hoogenhuyze, X. Krauss, H. Kruijssen, C. Storm] Summary: Nanterinone (UK-61,260) is a novel positive inotropic and balanced-type vasodilating drug, only partially based on phosphodiesterase III inhibition. Preliminary data from controlled studies suggest satisfactory long-term efficacy and safety. As its acute hemodynamic effects in humans are unknown, an oral dose of 2 mg nanterinone was studied in 14 patients with heart failure (NYHA class II-III) on chronic diuretic and angiotensin-converting enzyme (ACE) inhibitor treatment. Before the study, patients were on a 2 g saltbalanced diet, and they received their last medication 16 hours before each study day. Hemodynamic measurements were carried out before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, and 24 hours after administration of the study drug. All patients received placebo and nanterinone on 2 consecutive days. Following nanterinone, systemic vascular resistance decreased immediately from 1699±82 (mean±SEM) at baseline to 1368±80 at 1 hour. Changes persisted for 12 hours. Concomitantly, there was an immediate and significant fall in pulmonary wedge pressure to 38% of baseline at 1.5 hours, together with a 20% reduction in pulmonary artery pressure. Heart rate remained unchanged and arterial pressures showed only a short, significant decrease. Cardiac index rose significantly from 2.28±0.15 at baseline to a highest value of 2.65±0.14 1/min/m2 at 1 hour. Changes persisted for 3 hours. Placebo had no effct on these variables. As, in view of its potential venodilating properties, hemodynamic improvement by nanterinone may depend on pre-existing left ventricular filling pressure, patients were subsequently grouped according to baseline pulmonary wedge pressure of>12 mmHg (H-PCWP) and ≤12 mmHg (L-PCWP). Cardiac index improved by 26% in H-PCWP and by 17% in L-PCWP (NS). In contrast, PCWP fell more markedly in H-PWCP than in L-PCWP (40% and 23%, respectively, p<0.05). Thus, oral nanterinone results in a significant acute hemodynamic improvement and is well tolerated. Although changes in left ventricular filling pressure are more pronounced in patients with elevated preexisting PCWP, cardiac pump function improves equally in patients with normal or low left ventricular filling pressure at baseline. Kluwer Academic Publishers, 1996 heart failure nationallicence positive inotrope nationallicence phosphodiesterase inhibition nationallicence hemodynamics nationallicence humans nationallicence ealcium sensitization nationallicence Remme W. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut van der Ent M. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut Bartels G. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut van Schelven D. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut van Hoogenhuyze D. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut Krauss X. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut Kruijssen H. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut Storm C. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/2(1996-10-01), 137-144 0920-3206 10:2<137 1996 10 10557 https://doi.org/10.1007/BF00823591 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00823591 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Remme W. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- van der Ent M. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Bartels G. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- van Schelven D. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- van Hoogenhuyze D. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Krauss X. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Kruijssen H. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Storm C. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/2(1996-10-01), 137-144 0920-3206 10:2<137 1996 10 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer