Role of intrapartum hypoxia in carnitine nutritional status during the early neonatal period

Campoy, Cristina; Goicoechea, Alejandro; Peinado, J.M.; Pedrosa, Tatiana do Nascimento; Baena, Rosa Ma; López, Clara; Rivero, Miguel; Molina-Font, J. A.

doi:10.1016/s0378-3782(01)00212-2

Cited by 11 publications

(7 citation statements)

References 25 publications

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“…Thereby we detected decreases of free carnitine (C0) and decadienyl-L-carnitine (C10∶2) and an increase in mainly long chain acyl carnitines after hypoxia. This is in agreement with other data, where levels of free and total carnitine were lower and levels of long chain acyl carnitines were higher in asphyxiated newborn babies than in controls [18], [19]. It was speculated that they may serve as fuel for cerebral energy metabolism [20].…”

Section: Discussionsupporting

confidence: 92%

Metabolomic Analyses of Plasma Reveals New Insights into Asphyxia and Resuscitation in Pigs

et al. 2010

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BackgroundCurrently, a limited range of biochemical tests for hypoxia are in clinical use. Early diagnostic and functional biomarkers that mirror cellular metabolism and recovery during resuscitation are lacking. We hypothesized that the quantification of metabolites after hypoxia and resuscitation would enable the detection of markers of hypoxia as well as markers enabling the monitoring and evaluation of resuscitation strategies.Methods and FindingsHypoxemia of different durations was induced in newborn piglets before randomization for resuscitation with 21% or 100% oxygen for 15 min or prolonged hyperoxia. Metabolites were measured in plasma taken before and after hypoxia as well as after resuscitation. Lactate, pH and base deficit did not correlate with the duration of hypoxia. In contrast to these, we detected the ratios of alanine to branched chained amino acids (Ala/BCAA; R2.adj = 0.58, q-value<0.001) and of glycine to BCAA (Gly/BCAA; R2.adj = 0.45, q-value<0.005), which were highly correlated with the duration of hypoxia. Combinations of metabolites and ratios increased the correlation to R2adjust = 0.92. Reoxygenation with 100% oxygen delayed cellular metabolic recovery. Reoxygenation with different concentrations of oxygen reduced lactate levels to a similar extent. In contrast, metabolites of the Krebs cycle (which is directly linked to mitochondrial function) including alpha keto-glutarate, succinate and fumarate were significantly reduced at different rates depending on the resuscitation, showing a delay in recovery in the 100% reoxygenation groups. Additional metabolites showing different responses to reoxygenation include oxysterols and acylcarnitines (n = 8–11, q<0.001).ConclusionsThis study provides a novel strategy and set of biomarkers. It provides biochemical in vivo data that resuscitation with 100% oxygen delays cellular recovery. In addition, the oxysterol increase raises concerns about the safety of 100% O2 resuscitation. Our biomarkers can be used in a broad clinical setting for evaluation or the prediction of damage in conditions associated with low tissue oxygenation in both infancy and adulthood. These findings have to be validated in human trials.

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Section: Discussionsupporting

confidence: 92%

Metabolomic Analyses of Plasma Reveals New Insights into Asphyxia and Resuscitation in Pigs

et al. 2010

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“…asphyxia and in 35 healthy newborn infants in the post-partum 1 -7 days (Bayes et al, 2001). Although they did not find any difference for free carnitine levels between hypoxic and healthy infants as in our study, they had found higher levels of total and acylcarnitines in the hypoxic group.…”

Section: Discussioncontrasting

confidence: 80%

“…After the delivery, there is sudden interruption of the maternal-fetal carnitine transfer. The low supply of the carnitine and its precursors in addition to the immaturity of the liver make carnitine a very essential molecule for the newborns (Scaglia and Longo, 1999;Bayes et al, 2001). As all the enzymes taking part in b-oxidation in mitochondrial matrix, all tissues need sufficient amount of carnitine in order to avoid any disturbances in the energy metabolism.…”

Section: Introductionmentioning

confidence: 99%

“…As all the enzymes taking part in b-oxidation in mitochondrial matrix, all tissues need sufficient amount of carnitine in order to avoid any disturbances in the energy metabolism. Especially under situations such as fasting or stress, fatty acids are the most referred metabolic fuel (Borum, 1983;Siliprandi and Ciman, 1986;Bayes et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Serum Carnitine Levels in Newborns with Perinatal Asphyxia and Relation to Neurologic Prognosis

Ezgu¹,

Atalay²,

Hasanoğlu³

et al. 2004

Nutritional Neuroscience

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Neonatal hypoxic encephalopathy is one of the major causes of permanent neurological sequel. This study was conducted to investigate serum total, free and acylcarnitine levels in asphyxiated newborns with or without encephalopathy. Serum total, free and acylcarnitine levels were investigated in 21 newborns with and seven asphyxiated newborns without signs of encephalopathy. The newborns with encephalopathy were further divided into grade 1, 2 and 3 encephalopathy groups. Serum total and acylcarnitine concentrations of the whole encephalopathy group were significantly lower than the non-encephalopathy group (p = 0.042 for both). Serum total and acylcarnitine concentrations of grade 3 encephalopathy group were significantly lower than the non-encephalopathy group (p = 0.014 and p = 0.040, respectively). No significant differences were noticed for free carnitine levels. Total carnitine levels were positively correlated with birth weight and 10th minute apgar score, whereas acylcarnitine levels were found to correlate with cord blood pH and free carnitine levels with birth weight. Cord blood pH, and total carnitine levels were found to be the most significant determinants of the neurological outcome at one year of age. It was emphasized that carnitine deficiency could occur in severely affected asphyxiated newborns and it is related to the outcome at one year of age.

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“…Most of the inherited defects of long-chain fatty acid oxidation that develop secondary carnitine deficiency have a similar phenotype. The role of carnitine in placental metabolism and consequently in fetal development has not been investigated, although there is scant data suggesting carnitine deficiency leads to intrauterine growth retardation (7,8).…”

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confidence: 99%

Carnitine Content and Expression of Mitochondrial β-Oxidation Enzymes in Placentas of Wild-Type (OCTN2+/+) and OCTN2 Null (OCTN2−/−) Mice

et al. 2004

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Placenta requires energy to support its rapid growth, maturation, and transport function. Fatty acids are used as energy substrates in placenta, but little is known about the role played by carnitine in this process. We have investigated the role of carnitine in the expression of the enzymes involved in fatty acid ␤-oxidation in placenta of OCTN2 Ϫ/Ϫ mice with defective carnitine transporter (OCTN2). Heterozygous (OCTN2 ϩ/Ϫ ) female mice were mated with heterozygous (OCTN2 ϩ/Ϫ ) male mice. Pregnant mice were killed and fetuses and placentas were collected. Carnitine was measured using HPLC and tandem mass spectrometry. Immunohistochemistry was used to detect enzyme expression. Enzyme activities were measured spectrophotometrically. The fetal and placental weights were similar among the three genotypes (OCTN2 ϩ/ϩ , OCTN2 ϩ/Ϫ , and OCTN2 Ϫ/Ϫ ). The levels of carnitine were markedly reduced (Ͻ20%) in homozygous OCTN2 Ϫ/Ϫ null fetuses and placentas compared with wildtype OCTN2 ϩ/ϩ controls. However, carnitine concentration in placenta was 2-to 7-fold higher than in the fetus in all three genotypes. Immunohistochemistry revealed that ␤-oxidation enzymes are expressed in trophoblast cells. Catalytic activities of these enzymes were present at comparable levels in wild-type (OCTN2 ϩ/ϩ ) and homozygous (OCTN2 Ϫ/Ϫ ) mouse placentas, with the exception of SCHAD, for which activity was significantly higher in OCTN2 Ϫ/Ϫ placentas than in OCTN2 ϩ/ϩ placentas. These data show that placental OCTN2 is obligatory for accumulation of carnitine in placenta and fetus, that fatty acid ␤-oxidation enzymes are expressed in placenta, and that reduced carnitine levels up-regulate the expression of SCHAD in placenta. Carnitine is an obligatory cofactor for the transport of long-chain fatty acids into mitochondria for subsequent ␤-oxidation (1). Carnitine deficiency is defined as a metabolic state in which the carnitine concentration in plasma and tissues falls below 10 -20% of normal values. Biologic consequences of carnitine deficiency mimic primary ␤-oxidation defects (2). OCTN2 (also known as SLC22A5) is a plasma membrane transporter that mediates the Na ϩ -coupled entry of carnitine into mammalian cells (3). Absence of OCTN2 function leads to excessive loss of carnitine in the urine due to defective reabsorption of filtered carnitine and consequently causes carnitine deficiency. Genetic defects in OCTN2 are the cause of primary carnitine deficiency in humans, a condition associated with Received November 26, 2003; accepted March 30, 2004

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Role of intrapartum hypoxia in carnitine nutritional status during the early neonatal period

Cited by 11 publications

References 25 publications

Metabolomic Analyses of Plasma Reveals New Insights into Asphyxia and Resuscitation in Pigs

Metabolomic Analyses of Plasma Reveals New Insights into Asphyxia and Resuscitation in Pigs

Serum Carnitine Levels in Newborns with Perinatal Asphyxia and Relation to Neurologic Prognosis

Carnitine Content and Expression of Mitochondrial β-Oxidation Enzymes in Placentas of Wild-Type (OCTN2+/+) and OCTN2 Null (OCTN2−/−) Mice

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