Inspiratory Muscle Activation via High Frequency Spinal Cord Stimulation

6.项目概要/摘要 许多颈髓损伤患者终生依赖机械性康复支持。 虽然电刺激技术已经能够使一些患者免于机械通气， 绝大多数仍然需要使用。考虑到这些器械的显著缺点， 迫切需要各种选择。我们最近在初步的动物试验中证明， 可以用上胸高频（>200 Hz）脊髓刺激（HF-SCS）实现激活。 这种方法需要刺激与吸气运动神经元池突触的脊髓束。这 是一种新颖的和更生理的吸气肌激活方法，因为刺激发生在预刺激时， 运动神经元水平，允许在运动神经元池内处理刺激，导致更多的 生理募集模式因此，这项技术有可能提供一种更有效的方法， 吸气肌起搏然而，在临床试验之前，这项技术的一些重要方面， 需要进一步的鉴定。以下目的旨在评估该技术的生物学 通过评估最佳刺激范例和电极位置，HF-SCS的机制， 保持通风、最佳电极设计和长期安全性。 在目标I中，最佳刺激范例和电极位置导致吸气肌的激活， 肌肉将通过测量吸入体积和气道压力产生来确定。在客观 第二，HF-SCS的机制将通过吸气肌EMG测量进行评估，包括单次 运动单位记录和测量胸腔和腹部位移。这些结果将使我们 以检验我们的假设，即HF-SCS导致吸气肌激活的生理模式。脊髓 将进行消融研究以确定介导吸气运动神经元池的通路的位置 activation.在目标III中，电场测量将与建模技术结合使用， 确定最佳电极设计。在目标IV中，HF-SCS在维持排尿支持方面的有效性 将对长期的时间进行评估。在目标V中，我们计划使用新设计的电极 其将用于评估该方法在慢性动物模型中的长期安全性。刺激会被 提供18-24小时/天，持续3个月。在长期刺激后，脊髓的病理检查 脊髓结构，脊神经和肌肉将被承担。 这些研究的结果应该解决有关这项技术的重要基础科学问题， 动物，并为人类临床试验提供框架。一种更符合生理的吸气肌方法 激活可能减少依赖于机械通气的四肢瘫痪者的数量， 提高他们的生活质量。

6. Project Summary /Abstract Many patients with cervical spinal cord injury are dependent upon lifelong mechanical ventilatory support. While electrical stimulation techniques have been able to free some patients from mechanical ventilation, the vast majority still require their use. Given the significant disadvantages of these devices, additional pacing options are badly needed. We have recently demonstrated in preliminary animal testing that inspiratory muscle activation can be achieved with upper thoracic high frequency (>200 Hz) spinal cord stimulation (HF-SCS). This method entails stimulation of spinal cord tracts which synapse with the inspiratory motoneuron pools. This is a novel and more physiologic method of inspiratory muscle activation since stimulation occurs at a pre- motoneuron level, allowing for processing of the stimulus within the motoneuron pools resulting in a more physiologic recruitment pattern. This technique therefore has the potential to provide a more effective method of inspiratory muscle pacing. Prior to clinical trials, however, there are important aspects of this technique that require further characterization. The following objectives are designed to assess the biology of this technique by evaluating the optimal stimulus paradigm and electrode location, mechanism of HF-SCS, efficacy in terms of maintaining ventilation, optimal electrode design and, long term safety. In Objective I, optimal stimulus paradigm and electrode location resulting in activation of the inspiratory muscles will be determined by measurements of inspired volume and airway pressure generation. In Objective II, the mechanism of HF-SCS will be evaluated by inspiratory muscle EMG measurements including single motor unit recordings and measurements of rib cage and abdominal displacements. These results will allow us to test our hypothesis that HF-SCS results in a physiologic pattern of inspiratory muscle activation. Spinal cord ablation studies will be performed to determine the location of pathways mediating inspiratory motoneuron pool activation. In Objective III, electric field measurements will be used in conjunction with modeling techniques to determine optimal electrode designs. In Objective IV, the efficacy of HF-SCS in maintaining ventilatory support for prolonged time periods will be assessed. In Objective V, we plan to employ newly designed electrodes which will be used to assess the long term safety of this method in a chronic animal model. Stimulation will be provided for 18-24 hrs/day for 3 months. Following long term stimulation, pathologic examination of the spinal cord structures, spinal nerves and muscles will be undertaken. The results of these studies should resolve important basic science issues concerning this technique in animals, and provide the framework for human clinical trials. A more physiologic method of inspiratory muscle activation is likely to reduce the number of tetraplegics dependent upon mechanical ventilation and thereby improve their life quality.