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- W2004915765 abstract "Endothelin (ET-1) is an endothelium-derived peptide, which binds to two receptors, ETA and ETB. ET-1 has been postulated to play a role in the systemic vasoconstriction, which is a hallmark of CHF, based on increased circulating ET-1 levels and favorable responses to ET receptor antagonism. The primary objective of this study was to assess the safety and cardiovascular responses to a new potent, orally available, selective ETA receptor antagonist (ABT-627, Abbott) in patients (n=7) with NYHA class III-IV chronic heart failure (CHF). We investigated the safety and hemodynamic response to acute oral ABT-627 administration in a dose-titration study, 5 days after discontinuation of angiotensin converting enzyme (ACE) inhibitor. ABT-627 dosing ranged from 7-30 mg po. Compared to baseline, oral ABT-627 increased cardiac index (2.1-+0.2 to 3.6-+0.4 1/min/m 2, p=0.016) and decreased pulmonary capillary wedge pressure (23-+2 to 16-+2 mmHg, p=0.03) and systemic vascular resistance (37-+4 to 2I-+2 RU, p=0.016) with a trend for a reduction in pulmonary vascular resistance (6.6 + 1.2 to 2.7-+ 1.0 RU). These potent cardiovascular responses occurred without changes in arterial blood pressure and heart rate. ABT-627 was well tolerated by all subjects. We conclude that acute selective ETA receptor antagonism with the orally active ABT-627 has marked and favorable hemodynamic effects in patients with class III-IV CHF in the absence of ACE inhibition. This study importantly supports a role for the ETA receptor in the mediation of systemic vasoconstriction and the therapeutic role of ETA receptor antagonism in human CHF. 173 Pharmacokinetics of Levosimendan in Patients with Severe Cougestive Heart Failure Pertti J. Pentikainen,~ Saila Atuila, 2 Matfi Kivikko,1 Esa-Pekka Sandell?Tapio Aalto,1 Kimmo Luomanmaki, 1 Lasse Lehtonen2; iDepartment of Medicine, HeIsinki University Central Hospital, Helsinki, Finland, 2Research Center, Orion Pharma, Espoo, Finland" @default.
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- W2004915765 date "1999-09-01" @default.
- W2004915765 modified "2023-09-24" @default.
- W2004915765 title "Safety and efficacy of an orally active selective endothelin—A receptor antagonist in moderate-severe human chronic heart failure" @default.
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- W2004915765 doi "https://doi.org/10.1016/s1071-9164(99)91521-x" @default.
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