L-carnitine improvement of cardiac function is associated with a stimulation in glucose but not fatty acid metabolism in carnitine-deficient hearts.
OBJECTIVE
Increasing myocardial carnitine content can improve heart function in patients with carnitine deficiency. We were interested in determining the effects of L-carnitine on cardiac function and substrate metabolism in a rat model of carnitine deficiency.


METHODS
Carnitine deficiency was induced in male Sprague-Dawley rats by supplementing the drinking water with 20 mM sodium pivalate. Control animals received an equimolar concentration of sodium bicarbonate. Following treatment, cardiac function and myocardial substrate utilization were determined in isolated working hearts perfused with glucose and relevant levels of fatty acids. To increase tissue levels of carnitine, hearts were perfused with 5 mM L-carnitine for a period of 60 min.


RESULTS
Hearts from sodium pivalate-treated animals demonstrated a 60% reduction in total heart carnitine content, depressions in cardiac function and rates of palmitate oxidation, and elevated rates of glycolysis compared to control hearts. Treatment with L-carnitine increased total carnitine content and reversed the depression in cardiac function seen in carnitine-deficient hearts. However, this was not associated with any improvement in palmitate oxidation. Rates of glycolysis and glucose oxidation, on the other hand, were increased with L-carnitine.


CONCLUSIONS
Our findings indicate that acute L-carnitine treatment is of benefit to cardiac function in this model of secondary carnitine deficiency by increasing overall glucose utilization rather than normalizing fatty acid metabolism.
Broderick
T L
TL
Midwestern University, Department of Physiology, Downers Grove, IL 60515, USA.
Panagakis
G
G
DiDomenico
D
D
Gamble
J
J
Lopaschuk
G D
GD
Shug
A L
AL
Paulson
D J
DJ
D000818:Animals; D002331:Carnitine / Q000172:deficiency* / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010421:Pentanoic Acids; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D005227:Fatty Acids; D010421:Pentanoic Acids; C005566:pivalic acid; D005947:Glucose; D002331:Carnitine