Alterations in Metabolites Associated with Hypoxemia in Neonates and Infants with Congenital Heart Disease.
Alterations in Metabolites Associated with Hypoxemia in Neonates and Infants with Congenital Heart Disease.
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DOI：
10.32604/chd.2020.012219
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发表时间：
2020-09-07
影响因子：
0.3
通讯作者：
Davidson J
中科院分区：
文献类型：
--
作者：
Pagano E;Frank B;Jaggers J;Twite M;Urban TT;Klawitter J;Davidson J
(1)测量患有先天性心脏病的低氧血症与非低氧血症婴儿的代谢组的总体变化;（2）确定低氧血症中改变的代谢物和代谢途径。科罗拉多儿童医院82例年龄≤120天、需要手术的先天性心脏病婴儿心肺转流术前血清样本分析。根据术前氧饱和度将婴儿分为三组：非低氧血症（>92%）、轻度低氧血症（85-92%）和重度低氧血症（<85%）。使用串联质谱法分析165种靶向代谢物。偏最小二乘判别分析和t检验分别用于确定代谢谱和单个代谢物之间的差异。新生儿或较大婴儿的广泛代谢指纹不因低氧血症程度而异。低氧血症和非低氧血症新生儿之间有12种不同的代谢物，包括低氧血症新生儿中较低的甲基丙二酸（p = 2.44 × 10−4）、谷氨酸（p = 0.001）和次黄嘌呤（p = 0.003），以及较高的胸腺嘧啶（p = 8.67 × 10−4）和肌醇（p = 0.014）。个别代谢物并没有显着不同的年龄较大的婴儿之间有或没有低氧血症。我们没有发现证据支持与新生儿或较大婴儿的紫绀型先天性心脏病相关的整体代谢变化。然而，特定的代谢物区分低氧血症和非低氧血症新生儿。这些包括甲基丙二酸，以及已知在缺氧-复氧状态（次黄嘌呤）和慢性低氧状态（谷氨酸、胸腺嘧啶、肌醇）中发生变化的几种代谢物，可能代表紫绀型先天性心脏病新生儿低氧血症引发的特定代谢变化。
(1) To measure the global shift in the metabolome in hypoxemic versus non-hypoxemic infants with congenital heart disease; (2) To identify metabolites and metabolic pathways that are altered in hypoxemia. Analysis of serum samples obtained prior to cardiopulmonary bypass from 82 infants ≤120 days old with congenital heart disease requiring surgery at Children’s Hospital Colorado. Infants were divided into groups based on pre-operative oxygen saturations: non-hypoxemic (>92%), mild hypoxemia (85–92%), and severe hypoxemia (<85%). Tandem mass spectrometry was used to analyze 165 targeted metabolites. Partial least squares discriminant analysis and t-tests were used to determine differences among metabolic profiles and individual metabolites respectively. The broad metabolic fingerprint of neonates or older infants did not vary by degree of hypoxemia. There were 12 individual metabolites that differed between hypoxemic and non-hypoxemic neonates, including lower methylmalonic acid (p = 2.44 × 10−4), glutamate (p = 0.001), and hypoxanthine (p = 0.003), and higher thymine (p = 8.67 × 10−4) and myo-inositol (p = 0.014) seen in hypoxemic neonates. Individual metabolites did not vary significantly between older infants with or without hypoxemia. We did not find evidence supporting global metabolic changes associated with cyanotic congenital heart disease in neonates or older infants. However, specific metabolites did discriminate between hypoxemic and non-hypoxemic neonates. These include methylmalonic acid, as well as several metabolites known to change in hypoxia-reoxygenation states (hypoxanthine) and chronic hypoxemic states (glutamate, thymine, myo-inositol) and may represent specific metabolic changes triggered by hypoxemia among neonates with cyanotic congenital heart disease.