硬脊膜外脊髓电刺激器的实验设计

Stimulator for experimental use in epidural spinal cord stimulation

目的:临床研究已证实,脊髓不完全损伤患者接受硬脊膜外脊髓电刺激后,能增加其行走速度和行走时间,使能量代谢发生变化,脂肪代谢速率增加,碳水化合物代谢速率降低。建立一种用于硬脊膜外脊髓电刺激动物实验的实验系统,以进一步观察揭示这种作用的相应机制。方法:①硬脊膜外脊髓电刺激器基本原理和电路构成设计:硬件主要由单片机、人机接口电路、光电隔离电路、数模转换电路及波形调制电路5大部分组成。单片机采用美国ATMEL公司的AT89S51,片内带4KB的可系统编程的Flash只读程序存储器、高性能的CMOS8位单片机。系统中人机接口电路主要提供用户输入和实时显示参数。②确定刺激器的参数可调范围:电压幅值0～10V(每0.1V为一档,上下可调),频率500～1000Hz(每100Hz为一档,上下可调),波宽0～100μs(每5μs为一档,上下可调)。③选择刺激波形:选用电荷平衡的双相脉冲。④选择确定电极及其导线材料:以银作为电极和导线的材料(达到刺激点准确),医用硅胶封装电极(达到兼容性),电极导线封装在硅胶模具内,电极片暴露(达到接触并刺激脊髓)。电极片直径1.7mm,导线直径0.2mm,电极片间距3mm。⑤动物实验:与同济医院神经康复科共同完成。选取成年健康猫5只,选L4、L5腰椎腰膨大部位,局部麻醉下切开皮肤,分离棘突及周围组织,切断棘突及椎板,显露硬膜外腔脂肪及硬膜。电极植入硬膜外腔。刺激电极的导线与刺激器相连。由低电压低频率开始电刺激,逐步提高强度和频率。调换3个刺激电极的正负极,重复上述刺激。以受刺激节段支配肌肉发生颤搐为标准观察刺激效果。结果:①采用AT89S51单片机作为核心,可调参数范围宽泛。②根据动物反应提供灵活多变的双极性脉宽波形,安全可靠。③初期动物实验检测中,5只实验猫都在刺激电压幅值达到[(1±0.1)V,(700±100)μs,(40±5)Hz]时,肌肉出现轻微颤搐。加大幅值,肌肉体的颤搐程度逐渐加大。而通过不断改变频率、波宽两个参数来增加刺激强度,发现对动物体颤搐程度也有不同程度的改善。实验过程中动物无不良反应。结论:硬脊膜外脊髓电刺激器的设计满足硬脊膜外脊髓电刺激研究的需要,能根据实验所需参数提供灵活多变安全可靠的刺激波形,良好的人机接口提供方便可靠的操作方式,为硬脊膜外脊髓电刺激机制的深入研究提供了良好的实验仪器。

AIM： Clinical research has indicated that applying epidural spinal cord stimulation on patients with incomplete spinal-cord injury can improve their walk speed and endurance, modulate energy metabolism during walking by increasing fat metabolism and reducing carbohydrate metabolism. To discover the underlying mechanism, we designed an animal experiment system using in epidural spinal cord stimulation. METHODS： ①Principle of Epidural Spinal Cord Stimulator and circuit design： The hardware consisted of MCU, man-machine interface circuit, D/ A circuit and waveform circuit. The MCU was made use of AT89S51 produced by ATMEL of U,S. with 4 KB programmable Flash read only memory and high-performance CMOS 8 bits single chip. The man-machine interface circuit was mainly used to provide real time parameter and input to users.②Range of simulator parameters： 0-10 V voltage amplitude （each gear was 0.1 V, could be modulated up or down）, 500-1000 Hz frequency （each gear was 100 Hz, could be modulated up or down）, and 0-100 μs pulse width （each gear was 5μs, could be modulated up or down）. ③ Waveform of the stimulation： Charge balance dual pulse was selected. ④ Electrode and the material of its lead： Silver was used as the material of electrodes and leads （in order to make the stimulate point accurate）, and silica gel encapsulate was used as the electrodes to ensure compatibility. Electrodes and leads were encapsulated in the silica gel module and the electrode chips were exposed to touch and stimulate the spinal cord. The electrode chip was 1.7 mm in diameter, and the lead was 0.2 nun, the space between electrode chips was 3 mm. ⑤Animal experiment： It was collaborated with Department of Neurological Rehabilitation of Tongji Hospital. The L4 and L5 bulgy parts on the lumbar of 5 adult healthy cats were selected, and their skin was sliced off to separate backbone and surrounding tissue and cut off spinal process and vertebral plate under the circumstances of local anesthesia, then the epidural spinal cord fat and epidural spinal of the cats were unfolded. The electrode was planted into epidural spinal cord, and the lead of the electrode was connected to stimulator, The stimulation was given with low voltage and frequency, which was boosted step by step. The anode and cathode of the three electrodes were exchanged, and then the stimulation above was repeated. Whether the muscle in the stimulated section jerked or not was used to judge the stimulated effect. RESULTS： ①The AT89S51 MCU served as the core hod a wide modulated range, ②The feasible charge balance dual pulse obtained from the animal reaction was safety and reliable, ③In the early stage of the experiment, the 5 cats jerked slightly when the stimulate voltage reached abottt （1±0.1） V, （700±100） μs, （40±5） Hz. The bigger the value, the larger the degree of the muscle jerks, Increasing the stimulate intensi.ty in different extent by means of changing frequency and waveform width, could also change the degree of the muscle jerk, No bad effects were found in the cats during experiment. CONCLUSION： This simulator can meet all the needs in the research of epidural spinal cord stimulation and provide flexible and safe simulated voltage according to the needed parameters in the experiment, and its man, machine interface can make operation convenient. This simulator is a good device used in further research of epidural spinal cord stimulation,