L-CARNITINE IMPROVEMENT OF CARDIAC-FUNCTION IS ASSOCIATED WITH A STIMULATION IN GLUCOSE BUT NOT FATTY-ACID METABOLISM IN CARNITINE-DEFICIENT HEARTS

Objectives: 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 substra te metabolism in a rat model of carnitine deficiency. Methods: Carniti ne deficiency was induced in male Sprague-Dawley rats by supplementing the drinking water with 20 mM sodium pivalate. Control animals receiv ed an equimolar concentration of sodium bicarbonate. Following treatme nt, cardiac function and myocardial substrate utilization were determi ned in isolated working hearts perfused with glucose and relevant leve ls of fatty acids. To increase tissue levels of carnitine, hearts were perfused with 5 mM L-carnitine for a period of 60 min. Results: Heart s from sodium pivalate-treated animals demonstrated a 60% reduction in total heart carnitine content, depressions in cardiac function and ra tes of palmitate oxidation, and elevated rates of glycolysis compared to control hearts. Treatment with L-carnitine increased total carnitin e content and reversed the depression in cardiac function seen in carn itine-deficient hearts. However, this was not associated with any impr ovement in palmitate oxidation. Rates of glycolysis and glucose oxidat ion, on the other hand, were increased with L-carnitine. Conclusions: Our findings indicate that acute L-carnitine treatment is of benefit t o cardiac function in this model of secondary carnitine deficiency by increasing overall glucose utilization rather than normalizing fatty a cid metabolism.