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

7.项目概要/摘要 由于颈脊髓损伤，许多患者终身依赖机械性康复支持。 虽然电刺激技术在将一些患者从机械刺激中解放出来方面是有用的， 通风，绝大多数仍然依赖于这些设备。由于其明显的缺点， 迫切需要额外的起搏选择。我们已经在脊髓损伤的动物模型中证明了 上胸高频（~300 Hz）脊髓可实现吸气肌激活 低刺激幅度的高频刺激（HF-SCS）。这种独特而令人兴奋的创新方法涉及 刺激脊髓回路，导致吸气肌激活的更生理模式。 然而，该方法的关键重要方面需要在临床应用之前进行表征和分析。 特别是考虑到这种方法代表生命支持系统的事实，在目标1中， 计划评估长的下降吸气球脊髓纤维对疗效的可能参与， HF-SCS，在脊髓损伤的亚急性动物模型中。因为脊髓在经历了 可塑性超过这一时期，我们也将评估HF-SCS在慢性颈部半切大鼠的疗效 在8周的时间内建立模型。在目标2中，我们将使用 开发一个经过验证的计算模型，该模型将用于预测最佳刺激模式， 最佳电极设计;这些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 将验证从计算模型预测得出的范例。最佳刺激模式 应该导致每个吸气肌群的生理参与，正常的气体交换， 并且具有低电荷要求。在目标4中，我们将确定HF-SCS 通过评估运动单位募集顺序导致吸气肌的生理激活。在 目标5，我们将评估HF-SCS期间对向呼气肌被激活的程度。在 此外，对潜在非吸气肌激活的更详细分析将通过 评估HF-SCS期间呼吸的代谢成本。总之，这些研究的结果应 在临床试验之前解决有关HF-SCS的重要基础科学和实践问题。如果 成功地，HF-SCS可以提供吸气肌激活的更自然和有效的方法， 可能会减少依赖机械通气的四肢瘫痪患者的数量， 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.