PROPIONYL L-CARNITINE IMPROVEMENT OF HYPERTROPHIED HEART FUNCTION IS ACCOMPANIED BY AN INCREASE IN CARBOHYDRATE OXIDATION

Propionyl L-carnitine (PLC) is a naturally occurring derivative of L-carnitine that can improve hemodynamic function of hypertrophied rat hearts. The mechanism(s) responsible for the beneficial effects of PLC is not known, although improvement of myocardial energy metabolism has been suggested. In this study, we determined the effect of PLC on carbohydrate and fatty acid metabolism in hypertrophied rat hearts. Myocardial hypertrophy was produced by partial occlusion of the suprarenal aorta of juvenile rats. Over a subsequent 8-week period, a mild hypertrophy developed, resulting in a 17% increase in heart weight in these animals compared with the sham-operated control animals. Myocardial carnitine was decreased in hypertrophied hearts compared with hearts from sham-operated animals (4155+/-383 versus 5924+-570 nmol . g dry wt(-1), respectively; P less than or equal to.05). Perfusion of isolated working hearts for 60 minutes with buffer containing 1 mmol/L PLC increased carnitine content in hypertrophied hearts from 4155+/-383 to 7081+/-729 nmol . g dry wt(-1) (P less than or equal to.05). In the presence of 1.2 mmol/L palmitate, fatty acid oxidation rates were not decreased in the hypertrophied hearts compared with control hearts. PLC treatment did not alter rates of fatty acid oxidation in control hearts but did result in a small increase in rates in the hypertrophied hearts. The most dramatic effect of PLC treatment in hypertrophied hearts was an increase in glucose oxidation rates from 137+/-25 to 627+/-110 nmol . min(-1). g dry wt(-1) (P less than or equal to.05) and an increase in lactate oxidation rates from 119+/-17 to 252+/-47 nmol . min(-1). g dry wt(-1) (P less than or equal to.05). Glycolytic rates, which were already significantly elevated in hypertrophied hearts compared with control hearts, were not altered by PLC treatment. Overall ATP production from exogenous sources was increased by 64% in PLC-treated hypertrophic hearts and was accompanied by a significant increase in cardiac work. The main effect of PLC treatment was to increase the contribution of glucose oxidation to the relative rate of ATP production from 11.6% to 21.6%. The contribution of glucose and palmitate oxidation to ATP production was also determined in aortic-banded animals treated with 60 mg/kg PLC for an 8-week period. This treatment was also associated with a significant improvement in mechanical function in hearts isolated from these animals compared with untreated animals as well as an increase in the contribution of glucose oxidation to ATP production. Despite this improvement of cardiac work after chronic PLC treatment, no increase in palmitate oxidation was observed in hypertrophied hearts. These findings indicate that the beneficial effects of PLC in hypertrophied hearts can be accounted for by a stimulation of ATP production from carbohydrate oxidation rather than from fatty acid oxidation. The increase in carbohydrate oxidation may be a consequence of activation of the pyruvate dehydrogenase complex, by means of a reduction in the ratio of intramitochondrial acetyl coenzyme A to coenzyme A.