Studies in which subcellular systems were used suggest that neonatal myocardium has a sharply limited capacity to metabolize fatty acids. The relationship of these findings to the intact heart was tested on piglets, 8 h to 12 days of age. Left ventricular (LV) performance, O2 consumption (MVO2), and fatty acid (FA) uptake and oxidation were measured. Hearts were perfused at 70 cmH2O pressure with buffer containing 2% bovine serum albumin, insulin (100 microU/ml), 5 mM glucose, and 1.5 mM lactate. 14C-labeled palmitate was added (net FA, 0.5 mM). Washed erythrocytes were used to assure adequate O2 delivery. LV end-diastolic pressure (EDP) was controlled with a fluid-filled balloon. FA oxidation was estimated by measuring 14CO2 production. Hearts less than 24 h (group I, n = 6), those approximately 3 days (group II, n = 5), and those 6-12 days of age (group III, n = 10) were compared. Measurements at a low EDP (2-4 cmH2O) and at a higher EDP (7-9 cmH2O) were compared. At the low EDP, rates of FA oxidation for groups I-III averaged 30.0 +/- 3.0, 31.4 +/- 2.9, and 50.2 +/- 2.6 nmol.min-1.g-1, respectively. These values increased to 43.8 +/- 3.7, 42.6 +/- 2.5, and 63.8 +/- 4.0 nmol.min-1.g-1, respectively, at the higher EDP level (P less than 0.01 for each group). Thus within a few hours of birth, pig hearts are able to oxidize long-chain FA, and the rate of oxidation is linked to mechanical function. However, both the oxidation rate and the percentage of MVO2 accounted for by FA oxidation are greater in older hearts.

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High concentrations of adrenergic agonists are known to cause significant structural damage to the heart, accompanied by depressed cardiac performance. These studies were undertaken to further elucidate mechanisms that contribute to this process. Rabbits were infused with either norepinephrine (NE, 3 micrograms.min-1.kg-1 iv) for 90 min or with an equivalent volume of normal saline (controls). The heart was immediately extracted and studied as an isolated working heart preparation perfused with erythrocyte-enhanced buffer. Stroke work, coronary flow, and O2 metabolism were determined, and substrate oxidation was measured by [14C]glucose or palmitate. Stroke work performed by hearts exposed to NE was only 31% of controls (2.6 +/- 0.4 vs. 8.4 +/- 0.9 g.cm-1.g-1). This was matched by reductions in coronary flow and O2 metabolism. Glucose oxidation was reduced from 54.6 +/- 3.9 to 16.0 +/- 5.3 nmol.min-1.g-1, and palmitate oxidation from 49.8 +/- 5.3 to 21.0 +/- 4.1 nmol.min-1.g-1 in the NE group. However, ATP, creatine phosphate, glycogen, and triacylglycerol concentrations were identical with the control group. O2 delivery per unit substrate oxidation was not lower in the NE group, and O2 extraction did not differ significantly. These findings indicate that the markedly lower contractile performance of the hearts exposed to NE cannot be attributed to a deficiency of metabolic capacity or limitation of O2 or substrate availability because of vasospasm. In view of the brief time (90 min), it is unlikely that leukocyte accumulation was a major factor. The observations are consistent with NE-derived oxidant injury, possibly causing disordered excitation-contraction coupling.