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Inspiratory Muscle Activation via High Frequency Spinal Cord Stimulation

通过高频脊髓刺激激活吸气肌

基本信息

批准号：
8458146
负责人：
Anthony F. DiMarco
金额：
$ 54.01万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-15 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8458146
关键词：
Abdomen Ablation Adverse effects Animal Model Animal Testing Animals Anxiety Basic Science Bilateral Biology Breathing Canis familiaris Cervical spinal cord injury Chest Chronic Clinical Trials Corrosion Data Devices Disadvantaged Electric Stimulation Electrodes Environmental air flow Evaluation Frequencies Fright Future Generations Histologic Human Intercostal Muscles Life Location Measurement Mechanical Ventilators Mechanical ventilation Mechanics Mediating Metabolic Methods Modeling Motor Motor Neurons Motor Pathways Muscle Nerve Neurostimulation procedures of spinal cord tissue Paralysed Pathologic Pathway interactions Patients Pattern Physiological Preparation Production Property Quadriplegia Quality of life Research Respiratory Center Respiratory Diaphragm Safety Secondary to Speech Spinal Cord Spinal Cord Tract Spinal cord injury Spinal nerve structure Stimulus Structure Structure of phrenic nerve Synapses Techniques Testing Thoracic spinal cord structure Time Ventral thoracic nerve structure abstracting design electric field improved indexing neurodevelopment novel pressure rib bone structure stimulus processing

项目摘要

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.

6.项目总结/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。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Activation of inspiratory muscles via spinal cord stimulation.

DOI：
10.1016/j.resp.2013.06.001
发表时间：
2013-11-01
期刊：
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
影响因子：
2.3
作者：
DiMarco, Anthony F.;Kowalski, Krzysztof E.
通讯作者：
Kowalski, Krzysztof E.

Spinal pathways mediating phrenic activation during high frequency spinal cord stimulation.

DOI：
10.1016/j.resp.2012.12.003
发表时间：
2013-03-01
期刊：
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
影响因子：
2.3
作者：
DiMarco, Anthony F.;Kowalski, Krzysztof E.
通讯作者：
Kowalski, Krzysztof E.

Diaphragm activation via high frequency spinal cord stimulation in a rodent model of spinal cord injury.

DOI：
10.1016/j.expneurol.2013.03.006
发表时间：
2013-09
期刊：
EXPERIMENTAL NEUROLOGY
影响因子：
5.3
作者：
Kowalski, Krzysztof E.;Hsieh, Yee-Hsee;Dick, Thomas E.;DiMarco, Anthony F.
通讯作者：
DiMarco, Anthony F.

High frequency spinal cord stimulation-New method to restore cough.

DOI：
10.1016/j.resp.2016.07.001
发表时间：
2016-10
期刊：
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
影响因子：
2.3
作者：
Kowalski, K. E.;Romaniuk, J. R.;Brose, S.;Richmond, M. A.;Kowalski, T.;DiMarco, A. F.
通讯作者：
DiMarco, A. F.

Intercostal muscle pacing with high frequency spinal cord stimulation in dogs.