Marked changes in intermediary metabolism occur during development of the heart. In the fetus, the heart utilises lactate and glucose as its main energy substrates, while in the adult, fatty acids are the main energy substrate. The transition from carbohydrate to fatty acid metabolism is a complex process which involves maturation of mitochondrial processes and dramatic changes in circulating levels of fatty acids and lactate. In addition, developmental changes in the use of energy substrates also involve changes in the regulation of the enzymes involved in both carbohydrate and fatty acid utilisation. This paper reviews these changes in intermediary metabolism which occur during myocardial development. The metabolic differences that exist between immature and adult hearts may explain the observed differences in the ability of immature hearts to withstand hypoxaemia or ischaemia.

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Although epinephrine is widely used clinically, its effect on myocardial energy substrate preference in the intact heart has yet to be clearly defined. We determined the effects of epinephrine on glucose and fatty acid metabolism in isolated working rat hearts perfused with 11 mM glucose, 0.4 mM palmitate, and 100 muU/ml insulin at an 11.5-mmHg left atrial preload and a 60-mmHg aortic afterload. Glycolysis and glucose oxidation were measured in hearts perfused with [5-3H]glucose and [U-14C]glucose, whereas fatty acid oxidation was measured in hearts perfused with [1-14C]palmitate. Addition of 1 microM epinephrine resulted in a 53% increase in the heart rate-developed pressure product. Glycolysis increased dramatically following addition of epinephrine (a 272% increase), as did glucose oxidation (a 410% increase). In contrast, fatty acid oxidation increased by only 10%. Epinephrine treatment did not increase the amount of oxygen required to produce an equivalent amount of ATP; however, epinephrine did increase the uncoupling between glycolysis and glucose oxidation in these fatty acid-perfused hearts, resulting in a significant increase in H+ production from glucose metabolism. Overall ATP production in epinephrine-treated hearts increased 59%. The contribution of glucose (glycolysis and glucose oxidation) to ATP production increased from 13 to 36%, which was accompanied by a reciprocal decrease in the contribution of fatty acid oxidation to ATP production from 83 to 63%. The increase in glucose oxidation was accompanied by a significant increase in pyruvate dehydrogenase complex activity in the active form. We conclude that the increase in ATP required for contractile function following epinephrine treatment occurs through a preferential increase in glucose use.

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