Nerve transfer for urinary bladder reinnervation: Organ donor and cadaver studies

目的1：建立盆腔特定膀胱前支的功能性电刺激(FES) 神经支配膀胱引起膀胱压力升高心脏跳动，脑死亡 人体器官捐赠者。目的2：开发一种机器人辅助的腹腔镜膀胱神经重建术。 闭孔神经分支至盆腔神经前膀胱支的神经移位。这将形成 为未来神经移位手术恢复膀胱排空功能的临床试验奠定基础。 在过去的18年里，我们正在进行的犬类临床前研究试图开发外科方法来治疗 下运动神经元损伤的膀胱、尿道和肛门括约肌的再神经支配。我们有非凡的表现 成功，现在计划开始临床翻译。我们清楚地记录了神经功能的再支配 膀胱，通过电刺激转移神经诱导膀胱收缩来评估，当 神经再支配手术在权力下放后立即进行，21在1个月和3个月20 29由于这种临床前的成功，我们建议将临床移植到人类。 膀胱排空功能失控的患者。我们已经在身体上清楚地证明了神经转移 盆神经膀胱支支配膀胱在技术上是可行的 然而，在得出这些方法将导致功能性逼尿肌神经支配的结论之前，我们 需要确认这些特殊的盆腔神经膀胱支的解剖形态 人类与动物模型非常相似，因此刺激将导致有效的逼尿肌 收缩。这将为神经移植手术在人类身上取得成功提供最后的证据。 研究对象。对比开放腹腔镜术中使用的动物模型，建立了机器人辅助的 腹腔镜闭孔盆神经移位术在非防腐身体膀胱神经再支配中的应用 在临床试验之前为外科医生提供手术程序方面的专业知识，与 开放式手术，大大缩短了恢复时间，提高了临床疗效。 长期影响：在人体身体和心脏跳动器官捐赠者中成功确认将提供 有信心将神经转移到盆腔神经的这些膀胱分支将重新支配逼尿肌和 对膀胱失控的患者恢复膀胱排空功能。世界上没有普遍存在的 逼尿肌活动丧失的有效治疗方法，因此迫切需要确定有效的治疗方法 在这种情况下。本建议书中所述的研究将最终证明 人膀胱神经再支配以恢复膀胱排空功能和促进 开发适当的技术设施，以便于将此程序翻译给患者。

Aim 1: establish that functional electrical stimulation (FES) of specific anterior vesical branches of the pelvic nerve leading to the urinary bladder causes increased urinary bladder pressure in beating heart, brain dead human organ donors. Aim 2: develop a robotic-assisted laparoscopic approach for bladder reinnervation by nerve transfer of obturator nerve branches to anterior vesical branches of the pelvic nerve. This will form the foundation for a future clinical trial of nerve transfer surgery for restoration of bladder emptying function. Our ongoing preclinical canine studies over the past 18 years seek to develop surgical approaches to reinnervate the lower motor neuron-lesioned urinary bladder, urethra and anal sphincter. We had remarkable success and now plan to begin clinical translation. We clearly documented functional reinnervation of the bladder, assessed by induction of bladder contraction with electrical stimulation of transferred nerves when the reinnervation surgery is performed immediately after the decentralization,21 at one and three months20 and now at one year after decentralization.29 Because of this preclinical success, we propose clinical translation to human patients that have lost control of bladder emptying function. We have clearly demonstrated in cadavers that nerve transfer to the vesical branches of the pelvic nerve innervating to the urinary bladder is technically feasible using a variety of donor nerves.2,6,7 However, prior to drawing the conclusion that these methods will lead to functional detrusor reinnervation, we need to confirm that the anatomical configuration of these particular vesical branches of the pelvic nerve in humans is sufficiently similar to the animal model such that stimulation will result in effective detrusor contraction. This would provide the final evidence that the nerve transfer surgeries will be successful in human subjects. In contrast to the open laparoscopic approaches used in the animal model, establishing a robotic-assisted laparoscopic approach to obturator to pelvic nerve transfer for bladder reinnervation in non-embalmed cadavers will provide surgeons with expertise in the surgical procedures prior to a clinical trial and is expected, in comparison with the open procedure, to greatly reduce the recovery time and improve clinical outcomes. Long term impact: Successful confirmation in human cadavers and in beating heart organ donors will provide confidence that nerve transfer to these vesical branches of the pelvic nerve will reinnervate the detrusor and restore bladder emptying function to patients that have lost control of their bladder. There is no universally effective therapy for loss of detrusor activity, thus there is an urgent need to identify an effective treatment for this condition. The study described in this proposal will provide the final proof for the feasibility of reinnervation of the human urinary bladder for restoration of bladder emptying function and facilitate the development of adequate technical facility with this procedure to facilitate the translation of this to patients.