Delineation of the influence of propionylcarnitine on the accumulation of long-chain acylcarnitines and electrophysiologic derangements evoked by hypoxia in canine myocardium.
To investigate the potential influence on one analogue of carnitine on the electrophysiologic derangements elicited by myocardial ischemia and subsequent reperfusion, we evaluated whether increasing concentrations of propionylcarnitine would interact with carnitine acyltransferase I and thereby decrease the accumulation of long-chain acylcarnitines during hypoxia in isolated adult canine myocytes. Propionylcarnitine (1-100 microM) did not alter the sixfold reversible increase in long-chain acylcarnitines elicited by 10 minutes of hypoxia. Likewise, propionylcarnitine did not alter the reversal of the accumulation of long-chain acylcarnitines associated with reoxygenation of hypoxic myocytes. To assess whether analogues of carnitine could influence the development or reversal of the electrophysiologic derangements induced by hypoxia in adult canine epicardial tissue, selected concentrations of propionylcarnitine (1 microM to 10 mM) were administered prior to and during 15 minutes of hypoxic perfusion at 35 degrees C followed by 5-20 minutes of reoxygenation. Continuous intracellular transmembrane action potentials were recorded with glass microelectrodes. Administration of propionylcarnitine prior to and during hypoxia did not alter the electrophysiologic derangements elicited by hypoxia or subsequent reoxygenation. Therefore, propionylcarnitine does not influence the activity of carnitine acyltransferase I and does not alter the accumulation of long-chain acylcarnitines during hypoxia. Although propionylcarnitine may protect ischemic myocardium by enhancing the recovery of contractile function during reperfusion, propionylcarnitine does not attenuate any of the electrophysiologic alterations observed during hypoxia or subsequent reoxygenation in isolated tissue.
Yamada
K A
KA
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Dobmeyer
D J
DJ
Kanter
E M
EM
Priori
S G
SG
Corr
P B
PB
D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D003327:Coronary Disease / Q000378:metabolism; D004285:Dogs; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D000860:Hypoxia / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*
C003223:propionylcarnitine; D002331:Carnitine