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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-11-24
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0160-2446
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
849-55
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium.
pubmed:affiliation
Cardiology Unit, The Queen Elizabeth Hospital, Adelaide University, Woodville South, South Australia, 5011.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't