Spinal Cord Stimulation Reduces Ventricular Arrhythmias by Attenuating Reactive Gliosis and Activation of Spinal Interneurons.
Spinal Cord Stimulation Reduces Ventricular Arrhythmias by Attenuating Reactive Gliosis and Activation of Spinal Interneurons.
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脊髓刺激通过减少反应性神经胶质和脊柱中间神经元的激活来减少心室心律不齐。
DOI：
10.1016/j.jacep.2021.05.016
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Mahajan A
中科院分区：
文献类型：
--
作者：
Howard-Quijano K;Yamaguchi T;Gao F;Kuwabara Y;Puig S;Lundquist E;Salavatian S;Taylor B;Mahajan A
本研究探讨了在心脏缺血-再灌注（IR）触发的室性心律失常和通过脊髓刺激（SCS）进行的神经调节治疗期间脊髓神经元和胶质细胞的激活。心肌缺血引起心脏脊髓神经网络的变化，导致心脏性猝死。SCS的神经调节降低心脏交感神经兴奋;然而，分子机制仍然未知。将约克郡猪（n=16）随机分为对照组、IR组或IR+SCS组。将4极SCS电极导线置于T1-T4硬膜外腔，在IR前刺激30分钟（50 Hz，0.4 msec持续时间，90%运动阈值）。记录心脏电生理标测和室性心律失常评分（VAS）。胸段脊髓切片的免疫组织化学被用来映射和识别Fos阳性神经元和神经胶质细胞类型在IR与和没有SCS。IR增加心脏交感神经兴奋和心律失常（VAS = 6.2±0.9），在IR + SCS中减弱（VAS = 2.8±0.5，p=0.017）。IR增加了T1-T4中脊髓细胞Fos表达（Fos+细胞数对照= 23±2对IR=88±5，p<0.0001），其中最大的增加定位于T3，并且最大的%Fos+细胞是小胶质细胞和星形胶质细胞。IR + SCS减弱了Fos表达（62±4，p<0.01），主要是通过Fos+小胶质细胞和星形胶质细胞的减少，因为SCS还导致深背层中Fos+神经元的增加。在猪模型中，心脏IR与星形胶质细胞和小胶质细胞活化相关。我们的研究结果表明，先发制人的胸部SCS减少IR诱导的心脏交感神经兴奋和室性心律失常，通过衰减反应性胶质细胞增生和激活抑制性中间神经元在脊髓背角。心肌缺血-再灌注（IR）激活心脊髓神经网络，导致室性心律失常。脊髓刺激（SCS）降低心脏交感神经兴奋;然而，分子机制仍然未知。我们研究了IR触发室性心律失常和SCS神经调节过程中脊髓神经元和胶质细胞的激活。在随机分配至对照组、IR组或IR+SCS组的猪中，使用免疫组织化学测定神经胶质细胞和神经元细胞活性，同时记录心脏电生理标测和室性心律失常评分。研究表明，预先胸部SCS通过减弱脊髓背角的反应性胶质增生和激活抑制性中间神经元来减少IR诱导的室性心律失常。
This study investigated spinal cord neuronal and glial cell activation during cardiac ischemia-reperfusion (IR)-triggered ventricular arrhythmias and neuromodulation therapy by spinal cord stimulation (SCS) Myocardial ischemia induces changes in cardiospinal neural networks leading to sudden cardiac death. Neuromodulation with SCS decreases cardiac sympathoexcitation; however, the molecular mechanisms remain unknown. Yorkshire pigs (n=16) were randomized to Control, IR, or IR+SCS groups. A 4-pole SCS lead was placed in T1–T4 epidural space with stimulation for 30 mins prior to IR (50 Hz, 0.4msec duration, 90% motor threshold). Cardiac electrophysiological mapping and Ventricular Arrhythmia Score (VAS) were recorded. Immunohistochemistry of thoracic spinal sections was used to map and identify Fos-positive neuronal and glial cell types during IR with and without SCS. IR increased cardiac sympathoexcitation and arrhythmias (VAS = 6.2±0.9) which were attenuated in IR + SCS (VAS = 2.8±0.5, p=0.017). IR increased spinal cellular Fos expression (#Fos+ cells Control= 23±2 vs. IR=88±5, p<0.0001) in T1–T4, with the greatest increase localized to T3, and the greatest %Fos+ cells being microglia and astrocytes. Fos expression was attenuated by IR + SCS (62±4, p<0.01), primarily though reduction in Fos+ microglia and astrocytes, as SCS also led to increase in Fos+ neurons in deep dorsal laminae. In a porcine model, cardiac IR was associated with astrocyte and microglial cell activation. Our results suggest that preemptive thoracic SCS decreased IR-induced cardiac sympathoexcitation and ventricular arrhythmias through attenuation of reactive gliosis and activation of inhibitory interneurons in the dorsal horn of spinal cord. Myocardial ischemia-reperfusion (IR) activates cardiospinal neural networks leading to ventricular arrhythmias. Spinal cord stimulation (SCS) decreases cardiac sympathoexcitation; however, the molecular mechanisms remain unknown. We investigated spinal cord neuronal and glial cell activation during IR triggered ventricular arrhythmias and SCS neuromodulation. In pigs randomized to Control, IR, or IR+SCS groups, glial and neuronal cell activity was determined using immunohistochemistry while cardiac electrophysiologic mapping and ventricular arrhythmia scores were recorded. The study showed that preemptive thoracic SCS reduced IR-induced ventricular arrhythmias through attenuation of reactive gliosis and activation of inhibitory interneurons in the dorsal horn of spinal cord.
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影响因子：
20.1
作者：
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通讯作者：
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DOI：
10.1152/ajpheart.00129.2017
发表时间：
2017-08-01
影响因子：
4.8
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DOI：
10.1152/ajpregu.00899.2007
发表时间：
2008-11-01
影响因子：
2.8
作者：
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影响因子：
4.1
作者：
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