European Heart Journal Advance Access originally published online on December 20, 2004
European Heart Journal 2005 26(6):598-606; doi:10.1093/eurheartj/ehi082
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The effect of an angiotensin-converting enzyme inhibitor and a K+ATP channel opener on warm up angina
Division of Cardiology, KCL, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK
Received 6 November 2003; revised 10 November 2004; accepted 18 November 2004; online publish-ahead-of-print 20 December 2004.
* Corresponding author. Tel:+44 207 922 8191; fax:+44 207 960 5659. E-mail address: mike.marber{at}kcl.ac.uk
Aims In various models, angiotensin-converting enzyme (ACE) inhibitors and K+ATP channel openers can potentiate and mimic ischaemic preconditioning, respectively. Our aim was to determine whether these characteristics are shared by the phenomenon of warm up in angina, often regarded as a surrogate of ischaemic preconditioning.
Methods and results Twenty patients with ischaemic heart disease were assigned in a double blind, randomized cross-over design to equivalent pressor doses of nicorandil 20 mg bid, enalapril 10 mg bid, losartan 25 mg bid, or placebo for 3 days. Patients underwent three consecutive exercise tolerance tests on each medication separated by a 1-week interval. Each patient underwent 12 exercise tests in total and 13 patients completed the study. On each medication the second exercise was separated from the first by 15 min of rest and the third exercise was performed 90 min after the second to control for training. The time to 0.1 mV ST depression and rate pressure product at 0.1 mV ST depression increased significantly in all groups during exercise two compared with exercise one. Nicorandil reduced angina but did not attenuate this warm up effect. This benefit of first exercise waned by test three with placebo, losartan, and nicorandil, but not with enalapril.
Conclusion In contrast to predictions based on ischaemic preconditioning the magnitude of the warm up was apparently unaltered by nicorandil, losartan, or enalapril, however its duration seemed to be extended by enalapril. Thus ischaemic preconditioning and warm up angina are likely to have differing pharmacological profiles suggesting a diverse underlying mechanism.
Key Words: Angina • Exercise • ACE-inhibitor • K+ATP channel • Ischaemic preconditioning
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