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Haemodynamic dose‐response effects of UK‐52,046 in ischaemic disease with or without impaired left ventricular function.
Author(s) -
Silke B,
Zezulka AV,
Verma SP,
Tham TC,
Taylor SH
Publication year - 1990
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1990.tb03697.x
Subject(s) - medicine , hemodynamics , cardiac index , vascular resistance , regimen , pulmonary wedge pressure , cardiac output , supine position , blood pressure , cardiology , anesthesia , heart rate , mean arterial pressure
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)