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European Heart Journal 1989 10(3):227-234;
Copyright © 1989 by the European Society of Cardiology.
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© 1989 The European Society of Cardiology

The acute effects of intravenous xamoterol (‘corwin’ I. C. I. 118, 587) on resting and exercise haemodynamics in patients with mild to moderate heart failure

S. J. S. VIRK, N. H. ANFILOGOFF, N. LAWSON, A. M. SADLER, S. J. SMITH*, A. NUTTALL*, R. G. MURRAY, W. A. LITTLER and M. K. DAVIES

Department of Cardiovascular Medicine, University of Birmingham East Birmingham Hospital Birmingham
*I.C.I. Pharmaceuticals plc Alderley Park Macclesfield Cheshire, U.K.

Received 5 October 1988; .

Address for reprints: Dr S. J.S. Virk, Department of Cardiovascular Medicine, East Birmingham Hospital, Bordersley Green East, Birmingham, B9 5ST, U.K.

Abstract

The known properties of xamoterol, a partial beta,-agonist, provide a basis to pharmacologically modulate cardiac responses to variations in sympathetic tone.

Haemodynamic variables were assessed at rest and on exercise before and after intravenous xamoterol (0.2 mg kg-1), in 30 patients with mild to moderate cardiac failure. Xamoterol produced significant improvements in resting cardiac index (2.51 ± 0.15 to 2.80 ± 0.14 lmin-1 m-2; P< 0.001), stroke volume (62 ± 4 to 75 ± 5 ml beat-1; P <0.001) and stroke work index (42.4 ± 3.6 to 47.7 ± 3.9 g m beat-1 m-2; P <0.01). This occurred despite a significant reduction in heart rate (78 ± 3 to 74 ± 2 beats min-1;P <0.05). There were also significant reductions in systemic vascular resistance (1990± 141 to 1669± 112 dynes s-1 cm-5; P <0.01) and double product (1146 ± 46 to 1051 ± 41 mmHg min-1 x 10-1; P <0.05), with no significant changes in systolic blood pressure, pulmonary wedge pressure or ejection fraction. Xamoterol significantly attenuated the heart rate response to exercise (112 + 4 to 97 ± 3 beats min-1; P <0.001), with no impairment in the expected exercise induced increase in cardiac index. This was due to the significant increase in stroke volume from 81 ± 6 to 95 ± 7 ml beat (P <0.001). There were no significant changes in resting or exercise noradrenaline levels.

The enhanced cardiac performance seen at rest is due to the significant improvement in stroke volume. The improvements in stroke volume seen at rest are continued on exercise with no impairment in exercise-induced cardiac index, and a reduced double product.

Key Words: Xamoterol • Haemodynamics • heart failure • beta,-adrenoceptor partial agonist • beta-adrenoceptor blockade • exercise test • catecholamines


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