Carnitine palmitoyltransferase-i inhibition enhances the functional recovery of ischemic myocardium perfused in the absence of exogenous glucose. Madden, Michael C., Paul E. Wokowicz, Gerald M. Pohost, Jeanie B. McMillin, and Martin M. Pike. The Center for NMR Research and Development and the Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, The Department of Pathology and Lab Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030.
APStracts 2:0038H, 1995.
Inhibitors of carnitine palmitoyltransferase-I (CPT-I) have been shown to improve post-ischemic myocardial function. This improved recovery has been attributed either to decreased levels of long-chain acylcarnitines present in ischemic tissue or to increased oxidation of glucose in reperfused hearts. We investigated these two possibilities using oxfenicine, a CPT-I inhibitor, and alternate substrates which bypass long-chain fatty acid dependent metabolic pathways. Initially, isolated, perfused rat hearts were subjected to 20 min of ischemia followed by 40 min of reperfusion with either 10 mM glucose or 1.8 mM palmitate as substrate. Hearts perfused with palmitate had significantly decreased mechanical function during reperfusion when compared to glucose perfused hearts. In subsequent experiments, hearts were subjected to the same regimen of ischemia followed by reperfusion but using 2.4 mM hexanoate and 1.8 mM palmitate as exogenous substrates in the presence or absence of 2 mM oxfenicine. Hearts perfused with hexanoate and palmitate had significantly improved functional recovery when compared to palmitate-perfused hearts. Hearts subjected to ischemia followed by reperfusion with perfusates containing hexanoate, palmitate and oxfenicine demonstrated an additional small improvement in recovery during reperfusion when compared to hearts perfused solely with hexanoate and palmitate. 

Received 20 May 1993; accepted in final form 11 January 1995.
APS Manuscript Number H440-3.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.