Spinal Cord Stimulation: A Novel Method to Restore Breathing in Spinal Cord Injury

7.项目摘要/摘要 由于颈髓损伤，许多患者依赖终身机械通气支持。 虽然电刺激技术在将一些患者从机械刺激中解放出来是有用的 在通风方面，绝大多数仍依赖于这些设备。由于它们的显著缺点， 迫切需要更多的起搏选择。我们已经在一个脊髓损伤的动物模型中展示了 吸气肌的激活可以通过上胸高频(~300赫兹)脊髓来实现 低刺激幅度刺激(HF-SCS)。这一独特而令人兴奋的创新方法包括 刺激脊髓回路，导致吸气肌肉更具生理性的激活模式。 然而，这种方法的关键方面需要在临床之前进行表征和分析。 特别是考虑到这种方法代表着生命支持系统这一事实。在目标1中，我们 计划评估长下行吸气球脊髓纤维可能参与的疗效 HF-SCS，在亚急性脊髓损伤动物模型中。因为脊髓经历了显著的 在此期间，我们还将评估HF-SCS对慢性颈椎半横断大鼠的疗效。 为期8周的模特。在目标2中，我们将研究HF-SCS的机制 开发经过验证的计算模型，该模型将用于预测最优刺激范例和 优化的电极设计；这些设计将随后在我们的动物模型中进行测试。在目标3中，各种刺激 从计算模型预测得出的范例将得到验证。最优的刺激模式 应该导致每个吸气肌群的生理参与，正常的气体交换 并且对电荷的要求很低。在目标4中，我们将确定HF-SCS的程度 结果通过评估运动单位募集顺序，实现了吸气肌的生理激活。在……里面 目的5，我们将评估在HF-SCS期间相对呼气肌的激活程度。在……里面 此外，对潜在的非吸气性肌肉激活的更详细的分析将由 评估HF-SCS期间呼吸的代谢成本。总之，这些研究的结果应该是 在临床试验之前解决与HF-SCS相关的重要基础科学和实践问题。如果 成功的HF-SCS可能提供一种更自然、更有效的吸气肌激活方法 可能会减少依赖机械通风的四肢瘫痪患者的数量，从而显著 提高他们的生活质量。

7. Project Summary/Abstract Due to cervical spinal cord injury, many patients are dependent upon lifelong mechanical ventilatory support. While electrical stimulation techniques have been useful in liberating some patients from mechanical ventilation, the vast majority is still dependent on these devices. Due to their significant disadvantages, additional pacing options are badly needed. We have demonstrated in an animal model of spinal cord injury that inspiratory muscle activation can be achieved with upper thoracic high frequency (~300 Hz) spinal cord stimulation (HF-SCS) with low stimulus amplitudes. This unique and exciting innovative method involves stimulation of spinal cord circuitry, resulting in a more physiologic pattern of inspiratory muscle activation. However, critically important aspects of this method require characterization and analysis prior to clinical application, particularly in view of the fact that this method represents a life support system. In Objective 1, we plan to evaluate the possible involvement of long descending inspiratory bulbospinal fibers on the efficacy of HF-SCS, in a sub-acute animal model of spinal cord injury. Since the spinal cord undergoes significant plasticity beyond this period, we will also evaluate the efficacy of HF-SCS in a chronic cervical hemi-sected rat model over a period of 8 weeks. In Objective 2, we will examine the mechanism of HF-SCS with the development of a validated computational model, which will be used to predict optimal stimulus paradigms and optimal electrode designs; these will subsequently tested in our animal model. In Objective 3, various stimulus paradigms derived from computational model predictions will be validated. An optimal pattern of stimulation should result in the physiologic participation of each of the inspiratory muscle groups, normal gas exchange and have low electrical charge requirements. In Objective 4, we will determine the degree to which HF-SCS results in physiologic activation of the inspiratory muscles by assessing motor unit recruitment order. In Objective 5, we will assess the degree to which opposing expiratory muscles are activated during HF-SCS. In addition, a more detailed analysis of potential non-inspiratory muscle activation will be determined by evaluating the metabolic cost of breathing during HF-SCS. In summary, the results of these studies should resolve the important basic science and practical issues concerning HF-SCS in advance of clinical trials. If successful, HF-SCS may provide a more natural and effective method of inspiratory muscle activation and is likely to reduce the number of tetraplegics dependent upon mechanical ventilation and thereby significantly improve their life quality.