L-CARNITINE INCREASES GLUCOSE-METABOLISM AND MECHANICAL FUNCTION FOLLOWING ISCHEMIA IN DIABETIC RAT-HEART

Stimulation of glucose oxidation by L-carnitine improves mechanical re covery of ischaemic hearts from non-diabetic rats perfused with high l evels of fatty acids. The aim of this study was to determine whether L -carnitine also increases glucose oxidation and function in diabetic r at hearts, which have suppressed glucose metabolism. Methods: Isolated working hearts from six week streptozotocin diabetic and control rats were perfused with 11 mM (5-H-3/U-C-14)-glucose, 1.2 mM palmitate. He arts were paced at 260 beats.min(-1) during 60 min of low flow ischaem ia, and were then subjected to 30 min of aerobic reperfusion. Total my ocardial carnitine content in these hearts was first increased by a 60 min aerobic perfusion with 10 mM L-carnitine. Results: Steady state g lucose oxidation rates (measured as (CO2)-C-14 production) were depres sed in diabetic rat hearts compared to control hearts during the initi al aerobic period. However, L-carnitine treatment dramatically increas ed glucose oxidation rates in the diabetic rat hearts, as well as in c ontrol hearts. Glycolysis was also lower in diabetic rat hearts compar ed to control hearts, although L-carnitine treatment significantly inc reased glycolysis only in the diabetic rat hearts. L-carnitine treatme nt increased glycolysis during ischaemia, but again only in hearts fro m diabetic animals. During reperfusion, steady state rates of glucose oxidation and glycolysis returned to preischaemic values in both the c ontrol and diabetic groups. L-carnitine treatment stimulated glucose o xidation during reperfusion in control and diabetic rat hearts. Mechan ical function of control hearts returned to 38(SEM 9)% of preischaemic values, whereas in L-carnitine treated hearts function returned to 90 (7)% of preischaemic values. Recovery of function was 80(15)% of preis chaemic in the diabetic rat hearts, and was increased to 100% of preis chaemic function with L-carnitine. Conclusions: Carnitine improves rec overy of function of ischaemic non-diabetic rats by stimulating glucos e oxidation during reperfusion whereas it may be beneficial in diabeti c rat hearts by stimulating both glycolysis during ischaemia and gluco se oxidation during reperfusion.