Lipidomics Detection of Brain Cardiolipins in Plasma Is Associated With Outcome After Cardiac Arrest
Lipidomics Detection of Brain Cardiolipins in Plasma Is Associated With Outcome After Cardiac Arrest
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DOI：
10.1097/ccm.0000000000003636
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发表时间：
2019-04-01
影响因子：
8.8
通讯作者：
Bayir, Hulya
中科院分区：
文献类型：
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作者：
Anthonymuthu, Tamil S.;Kenny, Elizabeth M.;Bayir, Hulya
目的：脑线粒体功能障碍限制心脏骤停后神经系统的恢复。脑多不饱和心磷脂，线粒体-独特的和功能必需磷脂，具有前所未有的多样化。由于正常情况下血浆中不存在脑心磷脂，我们假设它们的出现与心脏骤停和自然循环恢复后早期脑损伤的严重程度有关。设计：观察性病例对照研究。环境：一个城市内有两个医疗中心。参与者（受试者）：我们招募了41名心脏骤停的成人患者，他们在再复苏后6小时内可以获得血液。通过异常值分析排除了两名受试者。10名健康受试者作为对照。Sprague-Dawley大鼠用于窒息性心脏骤停研究。干预措施:没有。测量和主要结果：我们建立了一种高分辨率液相色谱/质谱分析方法，并测定了39例心脏骤停患者、5例心肌梗死患者和10例健康对照者在6小时内（自然循环恢复）人脑、心脏和血浆中心磷脂的形态。脑评分来源于不同神经损伤和预后的患者血浆中发现的脑特异性心磷脂。采用大鼠心脏骤停模型，定量测定血浆、脑和心脏中的心磷脂。与心脏相比，人类大脑表现出高度多样化的心磷脂，这使得识别大脑特异性心磷脂成为可能。血浆中检测到26种脑特异性心磷脂中的9种与脑损伤相关。脑评分与早期神经损伤和预测出院神经/功能预后相关。心磷脂（70:5）成为预测损伤严重程度和预后的潜在护理点标志物。在大鼠心脏骤停时，海马心磷脂的显著减少与它们从大脑释放到体循环相对应。与5分钟无血流心脏骤停和初始对照组相比，大脑评分在10分钟内显著增加。结论：脑特异性心磷脂在自发循环恢复后早期在血浆中积累，与神经损伤成正比，是一种有希望的新型生物标志物。
Objectives: Brain mitochondrial dysfunction limits neurologic recovery after cardiac arrest. Brain polyunsaturated cardiolipins, mitochondria-unique and functionally essential phospholipids, have unprecedented diversification. Since brain cardiolipins are not present in plasma normally, we hypothesized their appearance would correlate with brain injury severity early after cardiac arrest and return of spontaneous circulation.Design: Observational case-control study.Setting: Two medical centers within one city. Participants (Subjects): We enrolled 41 adult cardiac arrest patients in whom blood could be obtained within 6 hours of re-suscitation. Two subjects were excluded following outlier analysis. Ten healthy subjects were controls. Sprague-Dawley rats were used in asphyxial cardiac arrest studies.Interventions: None.Measurements and Main Results: We developed a high-resolution liquid chromatography/mass spectrometry method and determined cardiolipins speciation in human brain, heart, and plasma within 6 hours of (return of spontaneous circulation) from 39 patients with cardiac arrest, 5 with myocardial infarction, and 10 healthy controls. Cerebral score was derived from brain-specific cardiolipins identified in plasma of patients with varying neurologic injury and outcome. Using a rat model of cardiac arrest, cardiolipins were quantified in plasma, brain, and heart. Human brain exhibited a highly diverse cardiolipinome compared with heart that allowed the identification of brainspecific cardiolipins. Nine of 26 brain-specific cardiolipins were detected in plasma and correlated with brain injury. The cerebral score correlated with early neurologic injury and predicted discharge neurologic/functional outcome. Cardiolipin (70: 5) emerged as a potential point-of-care marker predicting injury severity and outcome. In rat cardiac arrest, a significant reduction in hippocampal cardiolipins corresponded to their release from the brain into systemic circulation. Cerebral score was significantly increased in 10 minutes versus 5 minutes no-flow cardiac arrest and naive controls.Conclusions: Brain-specific cardiolipins accumulate in plasma early after return of spontaneous circulation and proportional to neurologic injury representing a promising novel biomarker.