title: Haemodynamic dose-response effects of UK-52,046 in ischaemic disease with or without impaired left ventricular function.
abstract: 1. The haemodynamic effects of a new cardioselective postsynaptic alpha 1-adrenoceptor antagonist UK-52,046, were evaluated in 25 patients with stable coronary disease, with or without impaired left ventricular function. At rest the haemodynamic effects to two dose-response regimens were determined. In an initial eight patients 0.125, 0.125 and 0.25 micrograms kg-1 were administered peripherally at 15 min intervals; the haemodynamic measurements were determined between 10 to 15 min after each dose. In a further 17 patients, the dose regimen was doubled yielding a cumulative dose-regimen of 0.25, 0.5 and 1.0 micrograms kg-1. The exercise effects were determined by comparison of measurements during 4 min of supine sub-maximal bicycle exercise at a fixed workload before and after drug treatment. 2. At rest, the lower dose regimen of UK-52,046 significantly reduced systemic mean arterial blood pressure (-5 mm Hg; P less than 0.05) and increased cardiac index (+0.2 l min-1 m-2, P less than 0.01). The higher dose regimen of UK-52,046 reduced systemic mean arterial blood pressure (-7 mm Hg; P less than 0.01), pulmonary artery occluded pressure (PAOP) (-2 mm Hg, P less than 0.01) and vascular resistance index (-314 dyn s cm-5 m2; P less than 0.05) with an increase in heart rate (+7%, P less than 0.05) and cardiac index (+0.2 l min-1 m-2, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: University Department of Cardiovascular Studies, General Infirmary, Leeds.
authors.forename: B
authors.initials: B
authors.lastname: Silke
authors.forename: A V
authors.initials: AV
authors.lastname: Zezulka
authors.forename: S P
authors.initials: SP
authors.lastname: Verma
authors.forename: T C
authors.initials: TC
authors.lastname: Tham
authors.forename: S H
authors.initials: SH
authors.lastname: Taylor
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000634:Aminoquinolines / Q000627:therapeutic use*; D000787:Angina Pectoris / Q000188:drug therapy / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D015444:Exercise; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011652:Pulmonary Circulation / Q000187:drug effects; D044005:Tetrahydroisoquinolines
chemical_list: D000317:Adrenergic alpha-Antagonists; D000634:Aminoquinolines; D044005:Tetrahydroisoquinolines; C058534:abanoquil