Combined Intercostal and Diaphragm Pacing

描述（由申请人提供）：通过双侧膈神经电刺激激活膈肌是一种有用的治疗方式，为依赖呼吸机的四肢瘫痪患者提供人工通气支持。不幸的是，由于部分或完全膈神经损伤，大多数依赖呼吸机的四肢瘫痪患者不适合膈神经起搏。根据最近完成的临床试验，通过放置在脊髓硬膜外表面的单个电极可以产生吸气肋间肌的协调收缩。由于与膈肌刺激相比，肋间肌起搏产生的吸气量较小，因此仅提供短期通气支持。然而，在依赖呼吸机的四肢瘫痪患者中，肋间和单侧膈肌联合起搏可以实现全职或接近全职的通气支持。在研究的4例患者中，每个患者都获得了全职或接近全职的呼吸支持。每个病人都报告说身体限制减少了，嗅觉改善了，在社交场合更自信了，说话能力也提高了。虽然取得了成功，但该试验中使用的设备有很大的局限性，妨碍了进一步的临床研究和商业化潜力。此外，我们在最近的研究中已经证明，通过肌内隔膜电极激活隔膜的侵入性较小。该项目第一阶段的具体目标包括设计、制造和实验台测试一种新的肋间起搏系统，该系统可以与凯斯西储大学（CWRU）植入式接收器-刺激器相连接，该系统：a)为肋间肌肉激活提供必要的刺激参数；b)可以通过肌肉内电极同步激活膈肌，从而实现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，该装置将消除现有系统的缺点，并使只有单侧膈神经功能的患者获得与接受双侧膈神经刺激的患者相同的益处。

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.