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Glycolysis is predominant source of myocardial ATP production immediately after birth
G D Lopaschuk1, M A Spafford, D R Marsh
1Department of Pediatrics, University of Alberta, Edmonton, Canada.
Insights
Neonatal rabbit hearts show a significant shift in energy metabolism, decreasing reliance on glycolysis and increasing fatty acid oxidation as they mature from 1 to 7 days old.
Area of Science:
- Cardiovascular Physiology
- Neonatal Metabolism
- Cardiac Energetics
Background:
- Cardiac energy metabolism undergoes significant changes during the neonatal period.
- Understanding substrate utilization in the developing heart is crucial for identifying potential metabolic interventions.
Purpose of the Study:
- To investigate the developmental changes in glycolytic flux and substrate oxidation (glucose, fatty acid, lactate) in isolated working rabbit hearts from 1-day-old and 7-day-old neonates.
- To determine the contribution of different metabolic pathways to ATP production in the neonatal heart.
Main Methods:
- Isolated working rabbit hearts from 1- and 7-day-old animals were perfused with media containing radiolabeled glucose, palmitate, or lactate.
- Glycolytic flux was measured by 3H2O production, and substrate oxidation was quantified by 14CO2 production.
- Insulin was included in the perfusate to simulate fed-state conditions.
Main Results:
- Glycolytic rates significantly decreased from 2730 to 580 nmol.min-1.g dry wt-1 between 1 and 7 days old.
- Palmitate oxidation dramatically increased from 22.6 to 305 nmol oxidized.min-1.g dry wt-1 with age.
- Lactate oxidation was robust in both age groups, increasing from 169 to 456 nmol.min-1.g dry wt-1.
- In 1-day-old hearts, glycolysis contributed 44% to ATP production, while glucose, palmitate, and lactate oxidation contributed 18%, 13%, and 25%, respectively.
Conclusions:
- The neonatal rabbit heart exhibits a marked developmental shift in substrate utilization, transitioning from a glycolytic-dominant metabolism to one that increasingly utilizes fatty acids.
- Lactate remains a significant energy source throughout this developmental period.
- These findings highlight the dynamic nature of cardiac energy metabolism during early postnatal life.
Abstract:
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 microU/ml insulin and either 1) 11 mM [U-14C/2-3H]glucose, 0.4 mM palmitate, 2 mM lactate; 2) 11 mM glucose, 0.4 mM [1-14C]palmitate, 2 mM lactate; or 3) 11 mM glucose, 0.4 mM palmitate, 2 mM [U-14C]lactate. Glycolytic rates (measured as 3H2O 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 14CO2 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 exogenous sources were derived from glycolysis, whereas 18, 13, and 25% were derived from glucose, palmitate, and lactate oxidation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)