Beneficial effect of carnitine on mechanical recovery of rat hearts reperfused after a transient period of global ischemia is accompanied by a stimulation of glucose oxidation.

Abstract

We have previously shown that increasing myocardial carnitine levels in fatty acid-perfused isolated working rat hearts dramatically increases glucose oxidation rates. Since high levels of fatty acids depress reperfusion recovery of ischemic hearts by inhibiting glucose oxidation, we determined what effect carnitine has on glucose oxidation during reperfusion of ischemic hearts. Isolated working rat hearts were perfused with 11 mM [5-3H/ul-14C]glucose, 1.2 mM palmitate, and 100 microU/ml insulin and subjected to a 35-minute period of global ischemia followed by aerobic reperfusion. Rates of glycolysis and glucose oxidation were determined by measuring tritiated water and 14CO2 production, respectively. Before ischemia, myocardial carnitine content was first increased by perfusing hearts during a 60-minute baseline aerobic perfusion with 10 mM L-carnitine. This resulted in a significant increase in total myocardial carnitine from 4,804 +/- 358 to 9,692 +/- 2,090 nmol/g dry wt (mean +/- SD). Glycolysis rates in carnitine-treated hearts were not significantly altered compared with control hearts during the aerobic perfusion (2,482 +/- 1,173 versus 1,840 +/- 1,365 nmol glucose.g dry wt-1 x min-1, respectively). In contrast, glucose oxidation rates in carnitine-treated hearts were significantly increased before ischemia compared with control hearts (471 +/- 209 versus 158 +/- 75 nmol glucose.g dry wt-1 x min-1, respectively). During reperfusion of previously ischemic hearts, glycolytic rates returned to preischemic values in both carnitine-treated and control hearts. Glucose oxidation rates also recovered to preischemic values in these hearts and remained significantly elevated in carnitine-treated hearts compared with control hearts (283 +/- 113 versus 130 +/- 27 nmol glucose.g dry wt-1 x min-1, respectively). Mechanical recovery in control hearts returned to 44% of preischemic values (measured as heart rate-peak systolic pressure product), whereas in carnitine-treated hearts, mechanical recovery returned to 71% of preischemic values. These results suggest that the beneficial effects of carnitine in the ischemic heart can be explained by the actions of this compound on overcoming fatty acid inhibition of glucose oxidation.