Lactate Metabolism of Isolated, Perfused Fetal, and Newborn Pig Hearts

Abstract

ABSTRACT. The role of lactate as an energy substrate in fetal (0.9 gestation) and newborn (2 day old) hearts was investigated in isolated, perfused hearts. Perfusions were performed with Krebs-Henseleit buffer supplemented with , glucose (5 mM) in combination with ~ar~in~concentrations of lactate. Isolated working heart ~erfusions. in which the u heart ejects the buffer at controlled pressure, were carried out with glucose (5 mM) alone and with glucose (5 mM) and lactate (5 mM) combined. With glucose as sole substrate, lactate was produced by the heart and glucose uptake accounted for approximately two-thirds of oxygen consumption. When both glucose and lactate were provided, lactate accounted for more than 80% of oxygen consumption and profoundly suppressed glucose uptake. ~urther-investigations using retrograde perfusion through the aorta demonstrated that lactate uptake was consistently observed when exogenous lactate concentrations exceeded 1.25 mM. Glucose uptake was suppressed with lactate concentrations as low as 0.5 mM and progressive suppression occurred with increasing lactate concentrations. Fetal and newborn pig hearts utilize lactate as a primary substrate for energy production when lactate concentrations are in the physiological range. (Pediatr Res 22: 552-556, 1987) Abbreviations ATP, adenosine triphosphate 'BSA, bovine serum albumin CP, creatine phosphate CVO, combined ventricular output ip, intraperitoneal PCA, perchloric acid lactate uptake by the fetal heart is sufficient to account for most of oxygen consumption by that organ (5).In previous studies using isolated, working perfused hearts, exogenous lactate and pyruvate uptake by newborn (<2 days old) pig hearts was sufficient to account for all of the oxygen consumption observed when these were the sole substrates provided (9). In contrast, glucose uptake was not adequate to account for all of oxygen consumption, even when provided as the sole exogenous substrate (10). Fatty acid uptake in the same model was reduced in fetal (0.9 gestation) as compared to newborn (2 day old) hearts (1 0, I I).The objective herein was to characterize the interactions of glucose and lactate as energy substrates in late fetal and newborn hearts. MATERIALS AND METHODSAnimals. Fetal (0.9 gestation) and neonatal piglets (2 days old) were obtained from local breeders. Pregnant sows or neonatal piglets were delivered to the animal facility. Subsequently, fetal piglets were delivered from sows by hysterotomy and handled as previously described ( 1 I). Fetal piglets were used within 4 h of hysterotomy, while neonatal piglets were used within 8 h of receipt.Perfusions. Hearts were removed quickly, chilled in a saline ice bath, and suspended in a perfusion system designed to study metabolism in isolated piglet hearts as previously described in detail (9). Briefly, fetal or newborn pigs were heparinized (Na heparin, 40 mg/kg body weight ip) and anesthetized (Na pentobarbital, 40 mg/kg body weight ip). Hearts were then removed and briefly perfused via the aorta with a def...

The Contribution of Glycolysis, Glucose Oxidation, Lactate Oxidation, and Fatty Acid Oxidation to ATP Production in Isolated Biventricular Working Hearts from 2-Week-Old Rabbits

“…We have also observed that pyruvate oxidation activity in heart homogenates from mice increases acutely after weaning (Itoi T, unpublished observations). Although glucose oxidation rates are low in immature hearts, lactate oxidation rates can be substantial (3,8). This may be related to the amount of specific isoforms of LDH in the heart.…”

“…Although glucose oxidation is a prominent source of ATP production in adult hearts, glucose oxidation rates are very low in the newborn heart (3). In contrast, lactate, which can be readily oxidized by fetal hearts (7,8), is a major source of ATP production in 1-and 7-d-old rabbit hearts (3). In adults, lactate oxidation is thought to be less important as a source of ATP production, although higher concentrations of lactate can reduce the rate of release and oxidation of fatty acids (9,10).…”

“…Lactate also decreases glucose oxidation, but to a lesser degree than fatty acid oxidation (10). Although lactate is a potent inhibitor of both glucose and palmitate oxidation in newborn rabbit hearts (3,8), the relationship between carbohydrate and fatty acid metabolism in the developing heart has still to be clearly established.…”

Cellular Expression of the Monocarboxylate Transporter (MCT) Family in the Placenta of Mice

“…Lactate and other monocarboxylates not only serve the major carbon sources for fatty acid synthesis but also are utilized as a metabolic energy source in various fetal tissues, such as the porcine heart [34], rat brain [35], and ovine liver [36]. The H + gradient-dependent lactate transport occurs in the brush-border membrane of the trophoblast in rat [37] and human placentas [5,7,8] and in the basal plasma membrane of the trophoblast in humans [5,38].…”

Cardiac nuclear receptors: architects of mitochondrial structure and function

“…However, very soon after birth the heart shifts to fatty acids as the major fuel substrate, coincident with the mitochondrial biogenic response (Figure 1 and refs. [5][6][7][8]. The level of glucose oxidation also increases (8).…”