An acute study of the electrophysiological and haemodynamic effects of intravenous UK-52,046, a novel alpha 1-adrenoceptor antagonist.

The acute electrophysiological and haemodynamic effects of UK-52,046, a novel alpha 1-adrenoceptor antagonist (0.5 microgram kg-1) were studied in 10 patients. Resting and paced conduction intervals, refractory periods, Wenckebach cycle length and sinus node recovery time were measured and compared with baseline values. Haemodynamic measurements including cardiac output were measured before and after drug administration. Changes in QRS interval (83 to 105 ms) and QRS duration during sinus rhythm (83 to 105 ms) or during constant atrial pacing (85 to 109 ms), were not significant (P greater than 0.05). Myocardial refractoriness and sinus node recovery time were not altered by the drug. Slight increases in mean heart rate (72.5 to 78.8 beats min-1), mean right atrial pressure (4.5 to 5.5 mm Hg) and mean cardiac output (5.4 l min-1 to 5.7 l min-1), were not significant (P greater than 0.05). Systolic and diastolic arterial pressure, cardiac work indices, and vascular resistance remained unchanged. These results demonstrate the safety of this drug given intravenously in a non-ischaemic setting, and warrant its further investigation as an antiarrhythmic agent in myocardial ischaemia.