CONTRIBUTION OF OXIDATIVE-METABOLISM AND GLYCOLYSIS TO ATP PRODUCTION IN HYPERTROPHIED HEARTS

The contribution of glycolysis and oxidative metabolism to ATP production was determined in isolated working hypertrophied hearts perfused with Krebs-Henseleit buffer containing 3% albumin, 0.4 mM palmitate, 0.5 mM lactate, and 11 mM glucose. Glycolysis and glucose oxidation were directly measured by perfusing hearts with [5-H-3/U-C-14]glucose and by measuring (H2O)-H-3 and (CO2)-C-14 production, respectively. Palmitate and lactate oxidation were determined by simultaneous measurement of (H2O)-H-3 and (CO2)-C-14 in hearts perfused with [9,10-H-3]palmitate and [U-C-14]lactate. At low workloads (60 mmHg aortic afterload), rates of palmitate oxidation were 47% lower in hypertrophied hearts than in control hearts, but palmitate oxidation remained the primary energy source in both groups, accounting for 55 and 69% of total ATP production, respectively. The contribution of glycolysis to ATP production was significantly higher in hypertrophied hearts (19%) than in control hearts (7%), whereas that of glucose and lactate oxidation did not differ between groups. During conditions of high work (120 mmHg aortic afterload), the extra ATP production required for mechanical function was obtained primarily from an increase in the oxidation of glucose and lactate in both groups. The contribution of palmitate oxidation to overall ATP production decreased in hypertrophied and control hearts (to 40 and 55% of overall ATP production, respectively) and was no longer significantly depressed in hypertrophied hearts. Glycolysis, on the other hand, was accelerated in control hearts to rates seen in the hypertrophied hearts. Thus a reduced contribution of fatty acid oxidation to energy production in hypertrophied rat hearts is accompanied by a compensatory increase in glycolysis during low work conditions. At higher workloads, the increased myocardial demand for ATP production overcomes these metabolic differences.