Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium
Author: Unger, S.
Kennedy, J.
McFadden-Lewis, K.
Minerds, K.
Murphy, G.
Horowitz, J.
Citation: Journal of Cardiovascular Pharmacology, 2005; 46(6):849-855
Publisher: Lippincott Williams & Wilkins
Issue Date: 2005
ISSN: 0160-2446
Statement of
Steven A. Unger, Jennifer A. Kennedy, Kate McFadden-Lewis, Kirsty Minerds, Geraldine A. Murphy and John D. Horowitz
Abstract: The antianginal agent perhexiline inhibits rat cardiac carnitine palmitoyltransferase-1 (CPT-1) and CPT-2, key enzymes for mitochondrial transport of long-chain fatty acids. We tested the hypothesis that perhexiline, in therapeutic concentrations (2 microM), inhibits palmitate oxidation and enhances glucose oxidation in isolated rat cardiomyocytes and in the working rat heart, thereby increasing efficiency of oxygen utilization. In isolated cardiomyocytes, perhexiline (2 microM) exerted no acute effects on palmitate oxidation, but after 48 hours pre-exposure oxidation was inhibited by perhexiline (2 to 10 microM) by 15% to 35% (P < 0.0002). In non-ischemic working rat hearts (3%BSA, 0.4 mM palmitate, 11 mM glucose, 100 microU/mL insulin) perhexiline (2 microM) had no significant acute effect on cardiac efficiency, palmitate or glucose oxidation, but 24 hours pretreatment with transdermal perhexiline increased cardiac work (by 29%, P < 0.05) and cardiac efficiency (by 30%, P < 0.02) without significant effects on palmitate oxidation. The selective CPT-1 inhibitor oxfenicine (2 mM) inhibited palmitate oxidation and enhanced glucose oxidation, but failed to enhance cardiac efficiency. In conclusion, in the non-ischemic working rat heart, perhexiline increases myocardial efficiency by a mechanism(s) that is largely or entirely independent of its effects on CPT. Effects on cardiac efficiency during ischemia, and with changes in fatty acid oxidation after longer perhexiline pretreatment remain to be determined.
Keywords: cardiac efficiency
carnitine palmitoyltransferase
Description: © 2005 Lippincott Williams & Wilkins, Inc.
DOI: 10.1097/01.fjc.0000190488.77434.f1
Published version:
Appears in Collections:Aurora harvest 6
Medicine publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.