Department of Molecular and Integrative Physiology, University of Michigan , Ann Arbor, Michigan.
Cardiovascular Center, University of Michigan , Ann Arbor, Michigan.
J Neurophysiol. 2019 Mar 1;121(3):842-852. doi: 10.1152/jn.00533.2018. Epub 2019 Jan 9.
Sudden death is an important but underrecognized consequence of stroke. Acute stroke can disturb central control of autonomic function and result in cardiac dysfunction and sudden death. Previous study showed that bilateral common carotid artery ligation (BCCAL) in the spontaneously hypertensive stroke-prone rat strain (SHRSP) is a well-established model for forebrain ischemic sudden death. This study aims to investigate the temporal dynamic changes in electrical activities of the brain and heart and functional interactions between the two vital organs following forebrain ischemia. EEG and ECG signals were simultaneously collected from nine SHRSP and eight Wistar-Kyoto (WKY) rats. RR interval was analyzed to investigate the cardiac response to brain ischemia. EEG power and coherence (CCoh) analysis were conducted to study the cortical response. Corticocardiac coherence (CCCoh) and directional connectivity (CCCon) were analyzed to determine brain-heart connection. Heart rate variability (HRV) was analyzed to evaluate autonomic functionality. BCCAL resulted in 100% mortality in SHRSP within 14 h, whereas no mortality was observed in WKY rats. The functionality of both the brain and the heart were significantly altered in SHRSP compared with WKY rats after BCCAL. SHRSP, but not WKY rats, exhibited intermittent surge of CCCoh, which paralleled the elevated CCCon and reduced HRV, following the onset of ischemia until sudden death. Elevated brain-heart coupling invariably associated with the disruption of the autonomic nervous system and the risk of sudden death. This study may improve our understanding of the mechanism of forebrain ischemia-induced sudden death. NEW & NOTEWORTHY This study demonstrates a marked surge of corticocardiac coupling in rats dying from focal cerebral ischemia, consistent with our earlier data in rats exposed to fatal asphyxia. Since the bidirectional electrical signal coupling (corticocardiac coherence) and communication (corticocardiac connectivity) between the brain and the heart are only identified in dying animals, they could be used as potential biomarkers to predict the risk of sudden death.
突然死亡是中风的一个重要但未被认识到的后果。急性中风会干扰自主功能的中枢控制，导致心功能障碍和突然死亡。先前的研究表明，自发性高血压卒中易患大鼠（SHRSP）的双侧颈总动脉结扎（BCCAL）是前脑缺血性猝死的一种成熟模型。本研究旨在探讨前脑缺血后大脑和心脏电活动的时间动态变化以及两个重要器官之间的功能相互作用。从 9 只 SHRSP 和 8 只 Wistar-Kyoto（WKY）大鼠中同时采集 EEG 和 ECG 信号。分析 RR 间期以研究心脏对脑缺血的反应。进行 EEG 功率和相干性（CCoh）分析以研究皮质反应。分析皮质-心脏相干性（CCCoh）和方向连通性（CCCon）以确定脑-心连接。分析心率变异性（HRV）以评估自主功能。BCCAL 导致 100%的 SHRSP 在 14 小时内死亡，而 WKY 大鼠则没有死亡。与 WKY 大鼠相比，BCCAL 后 SHRSP 的大脑和心脏功能均显著改变。与 WKY 大鼠不同，SHRSP 在缺血发作后直至突然死亡期间，间歇性出现 CCCoh 的激增，同时伴有 CCCon 升高和 HRV 降低。升高的脑-心耦合总是与自主神经系统的破坏和猝死的风险相关。本研究可能有助于我们理解前脑缺血引起的猝死的机制。
新的和值得注意的是，这项研究在死于局灶性脑缺血的大鼠中观察到皮质-心脏偶联的明显激增，与我们之前在暴露于致命窒息的大鼠中的数据一致。由于大脑和心脏之间的双向电信号耦合（皮质-心脏相干性）和通讯（皮质-心脏连通性）仅在濒死动物中被识别，因此它们可用作预测猝死风险的潜在生物标志物。
