GLYCOLYSIS IS PREDOMINANT SOURCE OF MYOCARDIAL ATP PRODUCTION IMMEDIATELY AFTER BIRTH

Glycolytic flux, as well as glucose, fatty acid, and lactate oxidation, was determined in isolated working hearts obtained from 1- and 7-day-old rabbits. One-day-old rabbit hearts were perfused via the inferior cava against a constant aortic and pulmonary arterial afterload, whereas hearts from 7-day-old rabbits were perfused via the left atria against a constant aortic afterload. Hearts were perfused with buffer containing 100-mu-U/ml insulin and either 1) 11mM [U-C-14/2-H-3]glucose, 0.4 mM palmitate, 2 mM lactate; 2) 11 mM glucose, 0.4 mM [1-C-14]palmitate, 2 mM lactate; or 3) 11 mM glucose, 0.4 mM palmitate, 2 mM [U-C-14]lactate. Glycolytic rates (measured as (H2O)-H-3 production) were high in 1-day-old hearts but decreased by 7 days (from 2,730 +/- 280 to 580 +/- 80 nmol.min-1.g dry wt-1). Rates of glucose oxidation (measured as (CO2)-C-14 production) were lower in both 1- and 7-day-old hearts (59 +/- 4.4 and 23 +/- 2 nmol.min-1.g dry wt-1). Palmitate oxidation rates were low in 1-day-old hearts but dramatically increased by 7 days (22.6 +/- 5.6 and 305 +/- 33 nmol oxidized.min-1.g dry wt-1, respectively). In contrast, lactate was readily oxidized by both 1- and 7-day-old hearts (169 +/- 14 and 456 +/- 52 nmol.min-1.g dry wt-1, respectively). In 1-day-old hearts, 44% of steady-state ATP production from exogeneous sources were derived from glycolysis, whereas 18, 13, and 25% were derived from glucose, palmitate, and lactate oxidation, respectively. In 7-day-old hearts, only 7% of ATP production from exogenous sources were derived from glycolysis, with 5, 39, and 49% being derived from glucose, palmitate, and lactate oxidation, respectively. These results demonstrate that immediately after birth in the rabbit, glycolysis is the major source of exogenous ATP production in the heart, whereas fatty acids are not readily oxidized. Within days of birth, however, there is a dramatic shift from glycolysis to both fatty acid and lactate oxidation as the primary sources of energy production.