SCI Bladder Management with E-STIM: Minimally Invasive and Staged Methods

使用 E-STIM 进行 SCI 膀胱治疗：微创分阶段方法

• 批准号: 7996779
• 负责人: James S. Walter
• 金额: --
• 依托单位: EDWARD HINES JR VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7996779
• 关键词: Acute; Adverse effects; Anesthesia procedures; Animal Model; Animals; Anus; Area; Bilateral; Bladder; Bladder Control; Canis familiaris; Catheters; Communities; Data; Development; Devices; Distal; Dorsal; Electric Stimulation; Electrodes; Evaluation; Fascia; Frequencies; Goals; Hospital Charges; Hospitals; Implant; Implanted Electrodes; Injury; Investigation; Isotonic Exercise; Laboratories; Letters; Life; Lower Extremity; Lower urinary tract; Measures; Mechanics; Methods; Mission; Modeling; Movement; Muscle; Needles; Nerve; Nerve Block; Neural Conduction; Obstruction; Ohio; Operative Surgical Procedures; Outcome; Palpation; Paraplegia; Patients; Pelvic floor structure; Physiologic pulse; Physiological; Pilot Projects; Protocols documentation; Rehabilitation therapy; Research; Resistance; Sacral nerve; Saline; Secondary to; Secure; Sphincter; Spinal cord injury; Staging; Students; Synapses; System; Techniques; Technology Transfer; Testing; Time; Tube; Urethra; Urethral Catheterization; Urethral sphincter; Urinary tract; Urination; Urine; Veterans; Water; abstracting; clinical application; cost; follow-up; instrument; minimally invasive; pressure; prevent; rectal; response; skeletal

DESCRIPTION (provided by applicant): Abstract Problem Statement: The Brindley Method is the only implantable stimulator available for micturition control following SCI. Although good outcomes have been shown with this device, it is limited by the need for invasive surgical procedures including a sacral afferent neurectomy. Alternatively, our long-term goal is to develop minimally invasive and staged stimulation methods for SCI bladder control. Our Objectives for this study includes the evaluation of a new Peterson, bipolar electrode that has been developed for this application by Synapse Biomedical Inc (Oberlin, OH). This electrode will be tested in two areas of SCI lower urinary tract problems: 1) short duration bladder contractions that do not empty the bladder; 2) high urethral resistance caused by skeletal urethral sphincter contractions that prevents urination. Proposed methods in anesthetized dogs with electrical stimulation (E-STIM) to produce high urethral resistance will include testing the new electrode on bladder and pudendal nerves separately and then in combination to determine effects on urination. Aim 1 (Bladder nerves): To investigate if moderate-frequency E- STIM of bladder nerves with Peterson bipolar and monopolar electrodes can produce high-pressure bladder contractions without pelvic floor activation. Aim 2(Pudendal nerves): To demonstrate that Peterson bipolar electrodes can be used to block the pudendal nerve with high-frequency E-STIM in a model of high urethral resistance (proximal pudendal nerve stimulation) and compare the blocking effects to a standard nerve cuff electrode. Aim 3: (combined nerves): Combined E-STIM of bladder and pudendal nerves in the model of high urethral resistance will result in urination with bladder emptying. Methods: Twelve dogs will be studied under anesthesia during this 1-year, pilot investigation. Animals will be instrumented for lower urinary tract recording and to evaluate the effects of E- STIM. Aims 1 to 3 will all be conducted in each of the animals. Physiological recording will include bladder, urethral, colonic, rectal and anal pressures. Also recorded will be urinated volume and flow as well as rating by palpation of pelvic floor and lower limb muscles and recording their movement with tubes filled water tubes. The bladder will be filled with 40 ml of isotonic saline for single nerve testing and 80% of cystometric capacity for combined nerve stimulation studies for urination. Probe electrodes will be used first to locate nerves followed by implanting the Peterson bipolar electrodes. Current-response testing will be conducted to show the effects of stimulation over a wide range of currents. Moderate frequency stimulation will be applied to the bladder nerves to produce bladder contractions and urination. 6 to 10 KHz frequency, square-wave stimulation of the pudendal nerves will be used to block the nerve and reduce urethral resistance. The animal model of high urethral resistance will be proximal pudendal nerve stimulation. Statistical analysis will be done by one-way ANOVA or Student t-test with paired data for single comparisons. Post hoc comparisons will be made using the Student-Neuman-Keuls test. All data will be presented as Mean + SEM. Relevance to the VA mission: The development of the bipolar Peterson electrode is an important step in technology transfer of minimally invasive and staged stimulation methods for bladder control following SCI. Current studies will show the acute effects of the Peterson bipolar electrode for this application. The minimally invasive methods needed to implant this electrode will assist in this long term goal. 1 PUBLIC HEALTH RELEVANCE: Significance of Research Initial hospital and rehabilitation costs for SCI can currently exceed $271,000 for paraplegia and follow-up hospital charges can exceed $27,000 per year.1,33 A significant amount of this cost is related to secondary complications of the lower urinary tract including urinary tract infections.5,6,34,35 Thus, the long-range goal of our laboratory is to develop methods for bladder management that do not rely on catheters. Both the staged and minimally invasive methods to be investigated here could contribute to this goal.1 Bladder nerve stimulation is a promising approach for inducing urination;2 the proposed pudendal nerve blocking techniques are promising for management of high urethral resistance.1 Thus, results from these studies will contribute to our long-term goals. Veteran with SCI have the same concerns as other patients with this injury living in the community. Thus, results will apply equally to Veterans with SCI.

描述（由申请人提供）： 摘要问题陈述：Brindley方法是唯一可用于SCI后排尿控制的植入式刺激器。尽管该器械的结局良好，但其受限于需要进行侵入性外科手术，包括骶骨传入神经切除术。或者，我们的长期目标是开发微创和分期刺激SCI膀胱控制的方法。本研究的目的包括评价Synapse Biomedical Inc（奥伯林，OH）为此应用开发的新型Peterson双极电极。该电极将在SCI下尿路问题的两个方面进行测试：1）不排空膀胱的短时间膀胱收缩; 2）由骨骼尿道括约肌收缩引起的阻止排尿的高尿道阻力。在电刺激（E-STIM）麻醉犬中产生高尿道阻力的拟议方法包括分别在膀胱和阴部神经上测试新电极，然后组合测试以确定对排尿的影响。目的1（膀胱神经）：研究使用Peterson双极和单极电极的膀胱神经的中频E-STIM是否可以在没有骨盆底激活的情况下产生高压膀胱收缩。目标2（阴部神经）：旨在证明Peterson双极电极可用于在高尿道阻力（近端阴部神经刺激）模型中使用高频E-STIM阻断阴部神经，并将阻断效果与标准神经袖带电极进行比较。目标3：（联合神经）：在高尿道阻力模型中，膀胱和阴部神经的联合E-STIM将导致排尿伴随膀胱排空。方法：12只犬将在麻醉下进行为期1年的初步研究。将对动物进行下尿路记录并评价E-STIM的作用。将在每只动物中进行目的1至3。生理记录将包括膀胱、尿道、结肠、直肠和肛门压力。还将记录排尿量和流量，以及通过触诊骨盆底和下肢肌肉进行评级，并用充满水管的管子记录它们的运动。膀胱将填充40 ml等渗盐水用于单神经测试，膀胱测压容量为80%用于排尿的联合神经刺激研究。首先使用穿刺电极定位神经，然后植入Peterson双极电极。将进行电流响应测试，以显示在宽电流范围内刺激的影响。将对膀胱神经施加中等频率的刺激以产生膀胱收缩和排尿。6至10 KHz频率，方波刺激阴部神经将用于阻断神经和降低尿道阻力。高尿道阻力的动物模型将是近端阴部神经刺激。统计分析将通过单因素ANOVA或Student t检验进行，配对数据用于单次比较。将使用Student-Neuman-Keuls检验进行事后比较。所有数据均以平均值+ SEM表示。与退伍军人事务部使命的相关性：双极Peterson电极的开发是SCI后膀胱控制微创和分期刺激方法技术转让的重要一步。目前的研究将显示Peterson双极电极在该应用中的急性效应。植入该电极所需的微创方法将有助于实现这一长期目标。1 公共卫生相关性： 研究的重要性目前脊髓损伤的初始住院和康复费用超过271，000美元（截瘫），后续住院费用每年超过27，000美元。1，33这笔费用中有很大一部分与下尿路的继发性并发症（包括尿路感染）有关。5，6，34，35因此，我们实验室的长期目标是开发不依赖于导管的膀胱管理方法。这里要研究的分期和微创方法都有助于实现这一目标。1膀胱神经刺激是一种很有前途的诱导排尿方法;2提出的阴部神经阻滞技术有希望用于管理高尿道阻力。1因此，这些研究的结果将有助于我们的长期目标。脊髓损伤的退伍军人有同样的关注与其他患者这种伤害生活在社区。因此，结果将同样适用于SCI退伍军人。