CONTRIBUTION OF OXIDATIVE-METABOLISM AND GLYCOLYSIS TO ATP PRODUCTIONIN HYPERTROPHIED HEARTS

The contribution of glycolysis and oxidative metabolism to ATP product ion was determined in isolated working hypertrophied hearts perfused w ith 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. Palmit ate and lactate oxidation were determined by simultaneous measurement of (H2O)-H-3 and (CO2)-C-14 in hearts perfused with [9,10-H-3]palmitat e and [U-C-14]lactate. At low workloads (60 mmHg aortic afterload), ra tes of palmitate oxidation were 47% lower in hypertrophied hearts than in control hearts, but palmitate oxidation remained the primary energ y source in both groups, accounting for 55 and 69% of total ATP produc tion, respectively. The contribution of glycolysis to ATP production w as significantly higher in hypertrophied hearts (19%) than in control hearts (7%), whereas that of glucose and lactate oxidation did not dif fer between groups. During conditions of high work (120 mmHg aortic af terload), the extra ATP production required for mechanical function wa s obtained primarily from an increase in the oxidation of glucose and lactate in both groups. The contribution of palmitate oxidation to ove rall 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 ot her hand, was accelerated in control hearts to rates seen in the hyper trophied hearts. Thus a reduced contribution of fatty acid oxidation t o energy production in hypertrophied rat hearts is accompanied by a co mpensatory increase in glycolysis during low work conditions. At highe r workloads, the increased myocardial demand for ATP production overco mes these metabolic differences.