Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, Los Angeles, California.
Department of Physical Therapy, University of Florida, Gainesville, Florida.
Am J Physiol Heart Circ Physiol. 2020 Apr 1;318(4):H830-H839. doi: 10.1152/ajpheart.00635.2019. Epub 2020 Feb 28.
Inherent and acquired factors determine the integrated autonomic response to cardiovascular stressors. Excessive sympathoexcitation to ischemic stress is a major contributor to the potential for sudden cardiac death. To define fundamental aspects of cardiac-related autonomic neural network interactions within the thoracic cord, specifically as related to modulating sympathetic preganglionic (SPN) neural activity. Adult, anesthetized Yorkshire pigs ( = 10) were implanted with penetrating high-density microarrays (64 electrodes) at the T2 level of the thoracic spinal cord to record extracellular potentials concurrently from left-sided dorsal horn (DH) and SPN neurons. Electrical stimulation of the T2 paravertebral chain allowed for antidromic identification of SPNs located in the intermediolateral cell column (57 of total 1,760 recorded neurons). Cardiac stressors included epicardial touch, occlusion of great vessels to transiently alter preload/afterload, and transient occlusion of the left anterior descending coronary artery (LAD). Spatial/temporal assessment of network interactions was characterized by cross-correlation analysis. While some DH neurons responded solely to changes in preload/afterload (8.5 ± 1.9%) or ischemic stress (10.5 ± 3.9%), the majority of cardiovascular-related DH neurons were multimodal (30.2 ± 4.7%) with ischemia sensitivity being one of the modalities (26.1 ± 4.7%). The sympathoexcitation associated with transient LAD occlusion was associated with increased correlations from baseline within DH neurons (2.43 ± 0.61 to 7.30 ± 1.84%, = 0.04) and between SPN to DH neurons (1.32 ± 0.78 to 7.24 ± 1.84%, = 0.02). DH to SPN network correlations were reduced during great vessel occlusion. In conclusion, increased intrasegmental network coherence within the thoracic spinal cord contributes to myocardial ischemia-induced sympathoexcitation. In an in vivo pig model, we demonstrate using novel high-resolution neural electrode arrays that increased intrasegmental network coherence within the thoracic spinal cord contributes to myocardial ischemia-induced sympathoexcitation.
内在和获得的因素决定了心血管应激的综合自主反应。对缺血性应激的过度交感兴奋是导致潜在心源性猝死的主要因素。为了定义胸段脊髓中心血管相关自主神经网络相互作用的基本方面,特别是与调节交感节前(SPN)神经元活动有关。成年麻醉约克夏猪(= 10)在 T2 水平的胸段脊髓植入穿透性高密度微阵列(64 个电极),同时记录左侧背角(DH)和 SPN 神经元的细胞外电位。T2 椎旁链的电刺激允许对位于中间外侧细胞柱中的 SPN 进行逆行识别(在记录的 1760 个神经元中,有 57 个)。心脏应激源包括心外膜触摸、大血管阻塞以暂时改变前负荷/后负荷以及左前降支冠状动脉(LAD)的短暂阻塞。通过互相关分析来描述网络相互作用的时空评估。虽然一些 DH 神经元仅对前负荷/后负荷的变化(8.5 ± 1.9%)或缺血性应激(10.5 ± 3.9%)做出反应,但大多数心血管相关的 DH 神经元都是多模态的(30.2 ± 4.7%),其中缺血敏感性是其中一种模态(26.1 ± 4.7%)。与短暂 LAD 阻塞相关的交感兴奋与 DH 神经元内的相关性从基线增加有关(2.43 ± 0.61 至 7.30 ± 1.84%,= 0.04)和 SPN 到 DH 神经元(1.32 ± 0.78 至 7.24 ± 1.84%,= 0.02)。大血管阻塞时 DH 到 SPN 网络的相关性降低。总之,胸段脊髓内节段内网络相干性的增加有助于心肌缺血引起的交感兴奋。在体内猪模型中,我们使用新型高分辨率神经电极阵列证明,胸段脊髓内节段内网络相干性的增加有助于心肌缺血引起的交感兴奋。