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European Heart Journal 1996 17(3):414-420;
Copyright © 1996 by the European Society of Cardiology.
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© 1996 The European Society of Cardiology

Anti-ischaemic efficacy of L-propionylcarnitine — a promising novel metabolic approach to ischaemia?

G. L. Bartels, W. J. Remme, K. J. Holwerda and D. A. C. M. Kruijssen

Sticares, Cardio vascular Research Foundation Rotterdam, The Netherlands

Received 29 June 1995; accepted 7 August 1995.

Correspondence: W. J. Remme, Sticares Foundation, P.O. Box 52006, 3007 LA Rotterdam, The Netherlands

Abstract

L-propionylcarnitine, a naturally occurring derivative of L-Carnitine, essential for mitochondrial fatty acid transport and high-energy phosphate exchange, acutely reduces myocardial ischaemia and improves ischaemia-induced cardiac dysfunction following intravenous administration. This randomized, crossover study was designed to compare the long-term anti-ischaemic effects of oral L-propionylcarnitine with diltiazem in patients with stable, exercise-induced angina. After a 2-week washout phase of anti-anginal medication and a 2-week single-blind placebo period, 46 patients were included in the study, 23 of whom received 1500 mg L-propionylcarnitine daily for 6 weeks, and 23 diltiazem (180 mg daily for 3 weeks, followed by 360 mg daily for 3 weeks), crossing over to the other treatment after a 1-week washout period. Three patients on L-propionylcarnitine and two on diltiazem discontinued. Both treatments resulted in comparable exercise duration (582 ± 35 s and 588 ± 33s, x ± SEM), time to 0·1 mV ST depression (436 ± 38 s and 465 ± 36 s), and increase in time to 0·1 mV ST depression from baseline (20% and 28%), L-propionylcarnitine and diltiazem, respectively.

Diltiazem decreased the rate-pressure product at rest and exercise, L-prOpionylcarnitine did not. Both compounds significantly reduced ST depression at maximal exercise [23% (L-propionylcarnitine) vs 35% (diltiazem), P<0·05 diltiazem vs L-propionylcarnitine]. Diltiazem increased the time to onset of angina by 22%. In contrast, no significant changes occurred with L-propionylcarnitine. During the study, anginal attacks were reduced by 70% and 57%, and nitroglycerin consumption decreased by 57% and 70%, L-proplonylcarnitine and diltiazem, respectively. Thus, both L-propionylcarnitine and (high-dose) diltiazem result in anti-ischaemic effects and decrease angina attacks in daily life. Although the effect of diltiazem on exerciseinduced ischaemia appears more pronounced than that of L-propionylcarnitine, this novel metabolic approach to ischaemia warrants further development.

(Eur Heart J 1996; 17: 414–420)

Key Words: L-propionylcarnitine • diltiazem • ischaemia • metabolic


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