Combined Intercostal and Diaphragm Pacing

描述（由申请人提供）：通过膈神经的双侧电刺激激活膈肌是一种有用的治疗方式，为呼吸机依赖性四肢瘫痪患者提供人工辅助支持。不幸的是，大多数呼吸机依赖性四肢瘫痪的患者由于部分或完全膈神经损伤而不适合膈神经起搏。基于最近完成的临床试验，吸气肋间肌肉的协调收缩可以通过放置在脊髓的硬膜外表面上的单个电极产生。由于与隔膜刺激相比产生较小的吸入体积，单独的肋间肌起搏仅提供短期的呼吸支持。然而，在呼吸机依赖性四肢瘫痪患者中，通过肋间和单侧膈肌联合起搏可以实现全时或接近全时的康复支持。在研究的4例患者中，均获得了全时或接近全时的辅助支持。每个病人都报告说身体限制减少，嗅觉改善，在社交场合更有信心，说话也有所改善。虽然成功，但本试验中使用的设备具有显著的局限性，排除了进一步的临床研究和商业化的潜力。此外，我们在最近的研究中已经证明，隔膜可以通过肌内隔膜电极以较低的侵入性激活。本项目第I阶段的具体目标包括新型肋间起搏系统的设计、制造和台架测试，该系统可与凯斯西储大学（CWRU）植入式接收器-刺激器连接，该系统：a）为肋间肌肉激活提供必要的刺激参数，B）可用于通过肌内电极同步激活膈肌，从而允许肋间和膈肌联合起搏。在第二阶段，该设备将首先在动物研究中进行测试，随后在人体临床试验中进行测试。如果成功，该器械将消除现有系统的缺点，并允许仅具有单侧膈肌功能的患者获得与接受双侧膈神经刺激的患者相同的受益。

DESCRIPTION (provided by applicant): Diaphragm activation via bilateral electrical stimulation of the phrenic nerves is a useful therapeutic modality providing artificial ventilatory support in ventilator dependent tetraplegic patients. Unfortunately, most patients with ventilator dependent quadriplegia are not candidates for phrenic nerve pacing due to partial or complete phrenic nerve injury. Based upon recently completed clinical trials, a coordinated contraction of the inspiratory intercostal muscles can be produced via a single electrode placed on the epidural surface of the spinal cord. Due to the production of smaller inspired volumes compared to diaphragm stimulation, intercostal muscle pacing alone provides only short term ventilatory support. However, full time or near full-time ventilatory support can be achieved with combined intercostal and unilateral diaphragm pacing in ventilator dependent tetraplegic patients. In each of 4 patients studied, full-time or near full-time ventilatory support was achieved. Each patient has reported less physical restriction, improved sense of smell, greater confidence in social situations and improved speech. While successful, the equipment utilized in this trial has significant limitations precluding further clinical studies and the potential for commercialization. Moreover, we have demonstrated in recent studies that the diaphragm can be activated less invasively via intramuscular diaphragm electrodes. The specific aims of Phase I of this project encompass the design, fabrication and bench testing of a new intercostal pacing system which can interface with the Case Western Reserve University (CWRU) implantable receiver-stimulator which: a) provides the necessary stimulus parameters for intercostal muscle activation and b) can be used to synchronously activate the diaphragm via intramuscular electrodes, allowing combined intercostal and diaphragm pacing. In Phase II, this device will be tested initially in animal studies and subsequently in human clinical trials. If successful, this device would eliminate the disadvantages of the currently existing systems and allow patients with only unilateral diaphragm function to achieve the same benefits as patients undergoing bilateral phrenic nerve stimulation.