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。尽管该装置已显示出良好的效果，但由于需要进行侵入性外科手术（包括骶传入神经切除术），因此它受到限制。另外，我们的长期目标是开发用于 SCI 膀胱控制的微创和分阶段刺激方法。我们本研究的目标包括评估 Synapse Biomedical Inc（俄亥俄州奥柏林）为此应用开发的新型 Peterson 双极电极。该电极将在 SCI 下尿路问题的两个领域进行测试：1) 短时膀胱收缩，不排空膀胱； 2) 骨骼性尿道括约肌收缩导致尿道阻力过高，导致排尿困难。拟议的方法是在麻醉狗中通过电刺激（E-STIM）产生高尿道阻力，包括分别测试膀胱和阴部神经上的新电极，然后组合测试以确定对排尿的影响。目标 1（膀胱神经）：研究用 Peterson 双极和单极电极对膀胱神经进行中频 E-STIM 是否可以在不激活盆底的情况下产生高压膀胱收缩。目标2（阴部神经）：证明Peterson双极电极可以在高尿道阻力（近端阴部神经刺激）模型中通过高频E-STIM阻断阴部神经，并与标准神经袖带电极的阻断效果进行比较。目标3：（联合神经）：在高尿道阻力模型中联合膀胱和阴部神经的E-STIM将导致膀胱排空排尿。方法：在为期一年的试点调查中，将在麻醉下对 12 只狗进行研究。将对动物进行下尿路记录并评估 E-STIM 的效果。目标 1 至 3 均将在每只动物中进行。生理记录包括膀胱、尿道、结肠、直肠和肛门压力。还记录排尿量和流量，以及通过触诊骨盆底和下肢肌肉进行评级，并用装满水的管子记录它们的运动。膀胱将充满 40 毫升等渗盐水以进行单神经测试，并充满 80% 的膀胱测压容量以进行排尿联合神经刺激研究。首先使用探针电极来定位神经，然后植入 Peterson 双极电极。将进行电流响应测试，以显示各种电流下的刺激效果。中频刺激膀胱神经以产生膀胱收缩和排尿。采用6～10KHz频率、方波刺激阴部神经，阻断神经，降低尿道阻力。高尿道阻力动物模型将阴部近端神经刺激。统计分析将通过单向方差分析或学生 t 检验以及配对数据进行单一比较。将使用 Student-Neuman-Keuls 检验进行事后比较。所有数据均以平均值 + SEM 形式呈现。与 VA 使命的相关性：双极 Peterson 电极的开发是 SCI 后用于膀胱控制的微创和分阶段刺激方法技术转让的重要一步。目前的研究将展示 Peterson 双极电极对此应用的急性影响。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： 研究的意义 目前，脊髓损伤的截瘫初始住院和康复费用可能超过 271,000 美元，后续住院费用每年可能超过 27,000 美元。1,33 其中很大一部分费用与下尿路继发性并发症（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导管的膀胱管理方法。这里要研究的分阶段方法和微创方法都可能有助于实现这一目标。1膀胱神经刺激是一种有前途的诱导排尿方法；2所提出的阴部神经阻断技术有望用于治疗高尿道阻力。1因此，这些研究的结果将有助于我们的长期目标。患有 SCI 的退伍军人与社区中其他患有这种损伤的患者有着同样的担忧。因此，结果同样适用于患有 SCI 的退伍军人。