We undertook this study to determine if the metabolism of exogenous glucose and glycogen in hypertrophied hearts differed from that in normal hearts during severe ischemia. Thus, rates of glycolysis (3H2O production) and oxidation (14CO2 production) from exogenous glucose and glycogen were measured in isolated working control (n = 13) and hypertrophied (n = 12) hearts from sham-operated and aortic-banded rats during 40 min of severe low-flow ischemia. Hearts, in which glycogen was prelabelled with [5-3H]- or [14C]-glucose, were paced and perfused with Krebs-Henseleit solution containing 1.2 mM palmitate, 5.5 mM [5-3H]- or [14C]-glucose (different from the isotope used to label glycogen), 0.5 mM lactate and 100 microU/ml insulin during ischemia. Rates of glycolysis from exogenous glucose (3301 +/- 122 v 2467 +/- 167 nmol/min/g dry wt, mean +/- S.E.M., P < 0.05) and glucose from glycogen (808 +/- 27 v 725 +/- 21 nmol/min/g dry wt, P < 0.05) were accelerated in hypertrophied hearts compared to control hearts. However, rates of oxidation of exogenous glucose and glucose from glycogen were not significantly different between the two groups. As observed in normoxic non-ischemic hearts, glucose from glycogen was preferentially oxidized compared to exogenous glucose. Additionally, rates of glycogen synthesis (167 +/- 7 v 140 +/- 9 nmol/min/g dry wt, P < 0.05) were increased in hypertrophied hearts compared to control hearts during severe low-flow ischemia indicating that glycogen turnover (i.e. simultaneous synthesis and degradation) was accelerated in the hypertrophied heart. Thus, we demonstrate that glucose utilization and glycogen turnover are accelerated in the hypertrophied heart during severe low-flow ischemia as compared to the normal heart.