Inspiratory Muscle Activation via High Frequency Spinal Cord Stimulation

描述（由申请人提供）：许多颈脊髓损伤患者终身依赖机械性辅助支持。虽然电刺激技术已经能够使一些患者免于机械通气，但绝大多数患者仍然需要使用它们。鉴于这些器械的显著缺点，迫切需要额外的起搏选项。我们最近在初步动物试验中证明，吸气肌激活可以通过上胸高频（>200 Hz）脊髓刺激（HF-SCS）实现。这种方法需要刺激与吸气运动神经元池突触的脊髓束。这是一种新颖且更生理的吸气肌激活方法，因为刺激发生在前运动神经元水平，允许在运动神经元池内处理刺激，从而产生更生理的募集模式。因此，该技术有可能提供更有效的吸气肌起搏方法。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表征。以下目的旨在通过评价最佳刺激范例和电极位置、HF-SCS机制、维持通气的有效性、最佳电极设计和长期安全性来评估该技术的生物学。在目标I中，将通过测量吸气量和气道压力生成来确定导致吸气肌激活的最佳刺激范例和电极位置。在目标II中，HF-SCS的机制将通过吸气肌EMG测量进行评价，包括单个运动单位记录以及肋骨和腹部位移的测量。这些结果将使我们能够测试我们的假设，即HF-SCS导致吸气肌激活的生理模式。将进行脊髓消融研究，以确定介导吸气运动神经元池激活的通路的位置。在目标III中，电场测量将与建模技术结合使用，以确定最佳电极设计。在目标IV中，将评估HF-SCS在长时间维持排便支持方面的有效性。在目标V中，我们计划采用新设计的电极，用于评估该方法在慢性动物模型中的长期安全性。将提供18-24小时/天的刺激，持续3个月。在长期刺激后，将对脊髓结构、脊神经和肌肉进行病理检查。这些研究的结果应该解决有关该技术在动物中的重要基础科学问题，并为人类临床试验提供框架。一种更具生理性的吸气肌激活方法可能会减少依赖机械通气的四肢瘫痪者的数量，从而提高他们的生活质量。 公共卫生相关性：继发于颈脊髓损伤的瘫痪患者通常依赖机械呼吸器来支持他们的呼吸。这些设备限制行动能力、令人不舒服、干扰正常言语的产生、因害怕断线而引发焦虑，从而降低生活质量。拟议的研究将调查新的电刺激方法，以恢复呼吸和消除机械通气的缺点。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Patients with paralysis secondary to cervical spinal cord injury are often dependent upon mechanical ventilators to support their breathing. These devices restrict mobility, are uncomfortable, interfere with the production of normal speech, provoke anxiety due to fear of disconnection and thereby reduce life quality. The proposed research will investigate new electrical stimulation methods to restore breathing and eliminate the disadvantages of mechanical ventilation.