Acylcarnitine accumulation does not correlate with reperfusion recovery in palmitate-perfused rat hearts.

Abstract

Carnitine palmitoyltransferase-I (CPT-I) inhibitors improve postischemic myocardial function either by decreasing muscle long-chain acylcarnitines (LCAC) during ischemia or by increasing oxidation of alternate substrates such as glucose during reperfusion. These possibilities were evaluated using oxfenicine, a CPT-I inhibitor, and alternate substrates that bypass carnitine-dependent metabolism. Isolated rat hearts subjected to 20 min of ischemia followed by 40 min of reperfusion with 1.8 mM palmitate as exogenous substrate recovered little function during reperfusion. Hearts made ischemic and reperfused with palmitate and 2.4 mM hexanoate as exogenous substrates had significantly improved reperfusion function compared to palmitate-perfused hearts. Addition of 2 mM oxfenicine to palmitate-hexanoate-perfused hearts gave an additional small improvement in reperfusion function. At the end of ischemia, the LCAC content of hearts perfused with palmitate or hexanoate and palmitate was identical. Palmitate-, hexanoate, and oxfenicine-perfused hearts had significantly decreased LCAC content at the end of ischemia compared with hexanoate-palmitate-perfused hearts. Therefore, depressed reperfusion function in long-chain fatty acid-perfused hearts can be ameliorated by alternate substrates, including medium-chain fatty acids. LCAC accumulation during ischemia apparently plays only a minor role in the postischemic dysfunction of long-chain fatty acid-perfused hearts.

• Authors: M C Madden, P E Wołkowicz, G M Pohost, J B McMillin, M M Pike
• Journal: The American journal of physiology (Am J Physiol) Vol. 268 Issue 6 Pt 2 Pg. H2505-12 (Jun 1995) ISSN: 0002-9513 [Print] United States
• PMID: 7611501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Caproates
• Palmitic Acids
• Phosphates
• Phosphocreatine
• hexanoic acid
• Palmitic Acid
• 4-hydroxyphenylglycine
• Adenosine Triphosphate
• Carnitine O-Palmitoyltransferase
• Glucose
• Carnitine
• Glycine

Topics

• Acylation
• Adenosine Triphosphate (metabolism)
• Animals
• Blood Pressure (drug effects)
• Caproates (pharmacology)
• Carnitine (analogs & derivatives, metabolism)
• Carnitine O-Palmitoyltransferase (antagonists & inhibitors)
• Energy Metabolism (drug effects)
• Glucose (pharmacology)
• Glycine (analogs & derivatives, pharmacology)
• Heart (drug effects, physiology, physiopathology)
• Heart Rate (drug effects)
• Hemodynamics (drug effects)
• Hydrogen-Ion Concentration
• Male
• Myocardial Ischemia (metabolism, physiopathology)
• Myocardial Reperfusion
• Myocardium (metabolism)
• Palmitic Acid
• Palmitic Acids (pharmacology)
• Phosphates (metabolism)
• Phosphocreatine (metabolism)
• Rats
• Rats, Sprague-Dawley
• Ventricular Function, Left (drug effects)