Data from: The role of plasma and urine metabolomics in identifying new biomarkers in severe newborn asphyxia: a study of asphyxiated newborn pigs following cardiopulmonary resuscitation

Background: Optimizing resuscitation is important to prevent morbidity and mortality from perinatal asphyxia. The metabolism of cells and tissues is severely disturbed during asphyxia and resuscitation, and metabolomic analyses provide a snapshot of many small molecular weight metabolites in body fluids or tissues. In this study metabolomics profiles were studied in newborn pigs that were asphyxiated and resuscitated using different protocols to identify biomarkers for subject characterization, intervention effects and possibly prognosis. Methods: A total of 125 newborn Noroc pigs were anesthetized, mechanically ventilated and inflicted progressive asphyxia until asystole. Pigs were randomized to resuscitation with a FiO2 0.21 or 1.0, different duration of ventilation before initiation of chest compressions (CC), and different CC to ventilation ratios. Plasma and urine samples were obtained at baseline, and 2 h and 4 h after return of spontaneous circulation (ROSC, heart rate > = 100 bpm). Metabolomics profiles of the samples were analyzed by nuclear magnetic resonance spectroscopy. Results: Plasma and urine showed severe metabolic alterations consistent with hypoxia and acidosis 2 h and 4 h after ROSC. Baseline plasma hypoxanthine and lipoprotein concentrations were inversely correlated to the duration of hypoxia sustained before asystole occurred, but there was no evidence for a differential metabolic response to the different resuscitation protocols or in terms of survival. Conclusions: Metabolic profiles of asphyxiated newborn pigs showed severe metabolic alterations. Consistent with previously published reports, we found no evidence of differences between established and alternative resuscitation protocols. Lactate and pyruvate may have a prognostic value, but have to be independently confirmed.

研究背景：优化复苏策略对于预防围产期窒息（perinatal asphyxia）所致的发病率与死亡率具有重要意义。窒息及复苏过程中，细胞与组织的代谢会受到严重干扰，而代谢组学（metabolomics）分析能够捕捉体液或组织中众多小分子代谢物的瞬时全貌。本研究对采用不同复苏方案处理的窒息新生仔猪的代谢组学特征谱进行分析，旨在筛选可用于受试对象分型、干预效果评估及预后预测的生物标志物（biomarker）。
研究方法：共125头新生诺罗克仔猪（Noroc pigs）接受麻醉、机械通气，并进行渐进式窒息造模直至心搏停止（asystole）。随后将仔猪随机分配至不同复苏组：分别采用吸入氧分数（FiO2）为0.21或1.0的氧浓度、胸外按压（chest compressions, CC）前不同通气时长、以及不同的胸外按压与通气比率进行复苏。分别于基线期、自主循环恢复（return of spontaneous circulation, ROSC，心率≥100次/分）后2小时及4小时采集血浆与尿液样本。采用核磁共振波谱法（nuclear magnetic resonance spectroscopy）对样本的代谢组学特征谱进行分析。
研究结果：ROSC后2小时及4小时，血浆与尿液样本均呈现出与缺氧及酸中毒相符的严重代谢紊乱。基线血浆中的次黄嘌呤（hypoxanthine）与脂蛋白（lipoprotein）浓度，与心搏停止前持续缺氧的时长呈负相关；但未观察到不同复苏方案间或不同存活结局间存在代谢应答差异的证据。
研究结论：窒息新生仔猪的代谢特征谱呈现出严重的代谢紊乱。与既往已发表的研究结果一致，本研究未发现标准复苏方案与备选复苏方案之间存在差异的证据。乳酸（lactate）与丙酮酸（pyruvate）或具有预后预测价值，但仍需开展独立研究予以验证。