Inspiratory Muscle Activation via High Frequency Spinal Cord Stimulation

6.项目摘要/摘要 许多颈髓损伤患者依赖终身机械通气支持。 虽然电刺激技术已经能够使一些患者摆脱机械通气，但 绝大多数人仍然需要使用它们。考虑到这些设备的显著缺点，额外的起搏 选择是非常必要的。我们最近在初步的动物实验中证明了吸气肌 激活可通过上胸高频(&gt；200赫兹)脊髓刺激(HF-SCS)实现。 这种方法需要刺激与吸气性运动神经元池突触的脊髓束。这 是一种新的更生理学的吸气肌肉激活方法，因为刺激发生在 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 生理学招募模式。因此，这种技术有可能提供一种更有效的方法 吸气式肌肉起搏。然而，在临床试验之前，这项技术有一些重要的方面 需要进一步的定性。以下目标旨在评估该技术的生物学特性 通过评估最优刺激范式和电极位置，高频-SCS的机制，有效性 维护通风、优化电极设计和长期安全。 在目标一中，最佳刺激范例和电极位置导致吸气激活 肌肉将通过测量吸入容量和产生的呼吸道压力来确定。在客观上 通过吸气肌肌电信号的测量来评价HF-SCS的发病机制。 运动单位记录和测量肋骨和腹部移位。这些结果将使我们能够 为了验证我们的假设，即HF-SCS导致吸气肌肉激活的生理模式。脊髓 将进行消融研究，以确定调节吸气运动神经元池的通路的位置。 激活。在目标三中，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，HF-SCS维持呼吸机支持的有效性 将对延长的时间段进行评估。在目标V中，我们计划使用新设计的电极 这将被用来评估这种方法在慢性动物模型中的长期安全性。刺激将是 提供18-24小时/天，为期3个月。在长期刺激后，脊柱的病理检查 将进行脊髓结构、脊神经和肌肉的检查。 这些研究的结果应该解决与这项技术有关的重要基础科学问题 动物，并为人类临床试验提供框架。一种更具生理性的吸气肌训练方法 激活可能会减少依赖机械通风的四肢瘫痪患者的数量，从而 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.