Haemodynamic dose-response effects of UK-52,046 in ischaemic disease with or without impaired left ventricular function.
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)
Silke
B
B
University Department of Cardiovascular Studies, General Infirmary, Leeds.
Zezulka
A V
AV
Verma
S P
SP
Tham
T C
TC
Taylor
S H
SH
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
D000317:Adrenergic alpha-Antagonists; D000634:Aminoquinolines; D044005:Tetrahydroisoquinolines; C058534:abanoquil