Fatty acid and glucose utilization in isolated, working newborn pig hearts

Werner, John C.; Whitman, Victor; Vary, Thomas C.; Fripp, Raymond R.; Musselman, Jude; Schuler, H. G.

doi:10.1152/ajpendo.1983.244.1.e19

Cited by 25 publications

(21 citation statements)

References 14 publications

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“…Our baseline rates of glycolysis are similar to those reported by Werner et al (18,32) for neonatal pig hearts, when wet to dry heart weight ratios are taken into account. With the induction of low-flow ischemia, glycolysis decreased =50-60% from baseline, which is comparable to the reduction in glycolysis observed by Neely et al (20) for isolated mature rat hearts subjected to severe ischemia.…”

Section: Discussionsupporting

confidence: 86%

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

et al. 1995

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Isolated, paced, isovolumetrically beating piglet hearts ( n = 37) underwent retrograde aortic perfusion with a crystalloid solution during three periods: 1) baseline (coronary perfusion pressure 60 mm Hg), 2) ischemia (coronary flow 10% of baseline for -80 min), and 3) reperfusion (perfusion pressure returned to baseline). In one group of hearts, glycolysis (using "H,o formation from [3H]glucose) was assessed. During baseline, peak systolic pressure (PSP) was 101.1 i 5.0 mm Hg, end diastolic pressure (EDP) 4.4 z 0.5 mm Hg, glycolysis 970.5 -C 65.3 nmol/min/g,,,, and myocardial glycogen 234.8 2 12.0 pmoll g,,,. During ischemia, PSI' decreased to 23.3 t 2.7 mm Hg, BDP increased to 12.3 2 0.7 mm Hg, myocardial glycogen decreased to 181.5 2 30.3 pmol/g,,,, and lactate (-154 pmoll g,,,) and glycerol (-930 nmol/g,,,) were released. Myocardial contracture correlated with a decrease in lactate release. Glycolysis decreased to -400 nmol/min/g,,, and remained stable, accounting for =SO% of the lactate producetl. During reperfusion, PSP recovered to 79.8 2 3.5 mm llg, EDP 6.6 2 1.7 mm Hg, and glycolysis 1103.9 + 81 nmol/rnin/g,,,. In a second group of hearts, with similar mechanical responses, giucose oxidation (using "CO, formation from ['4C]glucose) was evaluated. During baseline, glucose oxidation was 165.4 -t 15.9 nmol/min/g,,, and correlated closely (r = 0.957) with rnechanical activity. With ischemia, glucose oxidation decreased to =17Myocardial contracture represents a state of decreased diastolic compliance of the ventricle secondary to a depletion of high energy stores in the region of the contractile apparatus (1).With ischemia, contracture occurs as a consequence of myocardial underperfusion, which results in inadequate substrate delivery and impaired ATP production. Insufficient ATP leads to a progressive increase in the number of myocin-actin complexes that are unable to dissociate and to derangements in resting cytosolic calcium levels (2). (3,4). Little is known about myocardial contracture in the setting of low-flow ischemia, where hearts are beating, and there is washout of metabolites. Additionally, the modalities of energy production and utilization associated with contracture are poorly understood, yet these processes ultimately determine myocardial viability. An understanding of these processes in neonatal hearts has significant clinical ramifications, because contracture is thought to represent a precursor to an irreversible myocardial injury (5).The objectives of the present investigation were to study myocardial contracture in isolated, isovolumetrically beating, neonatal pig hearts subjected to normothermic, low-flow isch-

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Section: Discussionsupporting

confidence: 86%

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

et al. 1995

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“…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).…”

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confidence: 88%

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

Werner

Sicard

1987

Pediatr Res

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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...

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“…Inasmuch as the rate of oxidation of octanoate, octanoylcarnitine, or palmitoyl carnitine is similar in mitochondria from hearts of fetal, newborn, and adult pigs (12,20), the increase in fatty acid oxidation could be localized at the step of CPT 1, which catalyzes the synthesis of acylcarnitine. CPT I activity itself, however, does not change with age in pig hearts (2 I), suggesting that regulation of CPT 1 may be important.…”

Section: Source Of Atp Production In Newborn Hearts R ------------------mentioning

confidence: 99%

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

Itoi

Lopaschuk

1993

Pediatr Res

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ABSTRAm. Immediately after birth, glycolysis and lactate oxidation are the major source of ATP production in the rabbit heart. Although the ability of heart to oxidize fatty acid increases within days, glucose oxidation rates remain low in the first week after birth. To further examine the changes in energy substrate use in the newborn period, we developed a right and left ventricular isolated working heart model, in which 2-n k-old rabbit hearts were perfused with buffer containing 11 mM glucose, 0.8 mM palmitate, 0.5 mM lactate, and 100 pU/mL insulin. Hearts were perfused at a 7.5 mm Hg left atrial preload, a 4.5 mm Hg superior vena cava preload, a 30 mm Hg aortic afterload, and a 4.5 mm Hg pulmonary artery afterload. Glycolytic rates [measured as 'H20 production from (5-3H)-glucose] were 791 f 108 nmol/g dry weight. min-' (mean f SEM). Oxidation rates of glucose, lactate, and palmitate (measured as I4CO2 production from 14C substrates) were 94 f 15, 126 f 13, and 60 f 8 nmol/g dry weight.min-I, respectively. In these hearts, the majority of ATP production derived from exogenous sources was obtained from fatty acid oxidation (52%), whereas 11, 23, and 15% of ATP requirements were derived from glycolysis, glucose oxidation, and lactate oxidation, respectively. These studies demonstrate that by 2 wks of age in rabbits, fatty acids are the major source of energy in the heart. However, although the contribution of glucose oxidation to ATP production has increased compared with 1-or 7-d-old rabbit hearts, glucose oxidation rates are still low compared with adult hearts. (Pediatr Res 34: 735741,1993) Abbreviations CPT 1, carnitine palmitoyltransferase PDC, pyruvate dehydrogenase complex LDH, lactate dehydrogenase PAPSP, pulmonary arterial peak systolic pressure AoPSP, aortic arterial peak systolic pressure

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Fatty acid and glucose utilization in isolated, working newborn pig hearts

Cited by 25 publications

References 14 publications

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

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

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

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

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