Effect of glucose and fatty acid availability on neonatal and adult heart contractility.

Changes in contractility of newborn and adult hearts with different substrates were studied under oxygenation and hypoxia. Under oxygenation, insulin (50 mU/l) and low doses of fatty acids (sodium palmitate 0.12 mM) increased the differential ventricular pressure (DVP), while higher doses of fatty acids (from 0.3 to 1.5 mM) decreased it. However, when both low doses of fatty acids and insulin were added simultaneously, tension development decreased. Hypoxia reduced DVP, and low doses of fatty acids restored cardiac force. The contractile response to extracellular glucose concentrations changed during development, and sensitivity to high doses of fatty acids increased with age. In adult cardiomyocytes, glucose uptake was also inhibited by sodium palmitate under oxygenation when cardiac metabolism is fatty acid dependent, but not under hypoxia, when it consumes carbohydrates. Newborn cardiomyocytes consumed more glucose than adult cells, they did not respond to insulin, and palmitate did not completely inhibit glucose uptake neither under oxygenation nor under hypoxia. Substrate availability modified glucose uptake and contractility by independent mechanisms.