The effects of exogenous fatty acids on glucose uptake were assessed in isolated, working newborn pig hearts in which great vessel pressures were controlled (mean 55 mmHg) and oxygenated nutrient buffer was recirculated through the heart for 30 or 60 min. When palmitate (1.5 mM) or octanoate (1.0 mM) were added to buffer containing 10 mM glucose and 100 mU insulin/ml, glucose uptake, as measured by 3H2O production from D-[2-3H]glucose, was suppressed to less than one-half that observed when glucose alone was present. Increased tissue levels of glucose 6-phosphate, fructose 6-phosphate, and citrate following perfusion in the presence of exogenous fatty acids were consistent with decreased glycolytic activity due to inhibition of phosphofructokinase. Measurements of carnitine in perfused and unperfused hearts indicated that total carnitine levels in neonatal hearts are similar to those of adult pigs. Increased tissue levels of long-chain acyl carnitine, acetyl carnitine, and citrate in hearts perfused with palmitate and glucose in combination with extensive fatty acid uptake and marked suppression of glycolysis indicated that the newborn pig heart is capable of utilizing fatty acids as a primary energy source.

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The physiologic response to the chronic administration of digoxin was studied in 12 adult and 13 newborn sheep. Vascular pressures, cardiac output, isovolumic contraction phase indexes and systolic time intervals were measured before and after 2 weeks of digoxin therapy. Physiologic measurements were correlated with drug levels in plasma and myocardium. Resting myocardial function in newborns exceeded that in ewes. In ewes, the heart rate decreased from 98 to 74 beats/min, the preejection period (PEP) decreased from 76 to 57 msec, the ratio of PEP to left ventricular ejection time (LVET) decreased from 0.323 to 0.223 and dP/dt max increased from 2415 to 3460 mm Hg . sec-1 as plasma concentrations of digoxin increased to a mean of 1.8 ng/ml. Although the final steady-state plasma concentration of digoxin in newborn lambs averaged 1.7 ng/ml, cardiac output, PEP, PEP/LVET and dP/dt max did not change significantly from baseline values. These studies suggest that developmental differences in the physiologic response to digoxin are due either to a limited capacity for improvement in myocardial contractility shortly after birth or to an age-related difference in the effect of digoxin on myocardial tissue.

Oxidative metabolism and citrate synthase activity during the perinatal period were assessed in isolated rabbit heart mitochondria at 27 days’ gestation (27 dpc), 1 day postpartum (1 dpp) and 10 dpp. Oxygen consumption was measured during state 3 and state 4 respiration using the following substrates: glutamate, α-ketoglutarate, pyruvate/malate, succinate/rotenone, acetate, palmitylcarnitine, and palmityl CoA/carnitine. Results obtained from fetal and neonatal animals were compared to values obtained from adult left and right ventricles. Rates of state 3 oxygen consumption per milligram mitochondrial protein using tricarboxylic acid cycle intermediates or palmitylcarnitine were higher in both 1 and 10 dpp animals than in either left or right ventricles. Respiratory activity per milligram mitochondrial protein using these substrates was similar in 27 dpc fetuses and adult left ventricles. The rate of oxidation of palmityl CoA was lower in fetal mitochondria than in adult left ventricle, indicating that the capacity for conversion of long-chain fatty acyl CoA to acylcarnitine necessary for transport of fatty substrates into the mitochondria is decreased in fetal hearts. Increases in myocardial citrate synthase corresponded to increases in mitochondrial mass reported by other investigators.

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