Ventricular function and fatty acid metabolism in neonatal piglet heart

Abstract

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.

Reducing Equivalent Shuttles in Developing Porcine Myocardium: Enhanced Capacity in the Newborn Heart

“…Elegant studies by Lopaschuk et al (37) found that, when 1-d-old rabbit hearts were perfused with glucose, lactate, and palmitate as substrates, nearly half of the ATP produced was derived from glucose entering glycolysis with an additional 25% coming from lactate oxidation. Similar results have been found in newborn porcine myocardium (38,39). Using isolated, perfused neonatal porcine heart, it has been shown that less than a third of myocardial ATP is produced via fatty acid oxidation when glucose and lactate are also available (38).…”

“…Similar results have been found in newborn porcine myocardium (38,39). Using isolated, perfused neonatal porcine heart, it has been shown that less than a third of myocardial ATP is produced via fatty acid oxidation when glucose and lactate are also available (38). Even at incrcased workloads, the proportion of ATP produced via fatty acid oxidation remained stable (38).…”

Hepatic ketogenesis in newborn pigs is limited by low mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity

“…It is noteworthy that the limitation of fatty acid oxidation was only restricted to the liver of newborn pigs, because fatty acid oxidation develops normally after birth in extra-hepatic tissues (Bieber et al, 1973;Wolfe et al, 1978;Ascuitto et al, 1989;Werner et al, 1989).…”

Mechanical and Metabolic Characterization of Ischemic Contracture in the Neonatal Pig Heart

“…from the Thebesian circulation, was vented through an apical stab wound. This maneuver reduces the possibility that a fluid collection around the balloon could alter EDP (9)(10)(11).…”

“…Oxidation of exogenously supplied glucose was estimated by measuring 14C0, production (liberated at pyruvate dehydrogenase and the Krebs cycle) frorn glucose (100 pCi/L), using the method we have described previously (9). A 3-mL sample of perfusate was obtained anaerobically, and injected into a stoppered Erlenmeyer flask containing 1 N HC1 (to release CO,) and a center well with Hyamine hydroxide (to collect CO,).…”