Neurophysiology and Biomechanics of Urethra in SUI

SUI 尿道的神经生理学和生物力学

基本信息

批准号：
6761522
负责人：
NAOKI YOSHIMURA
金额：
$ 34.14万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-04-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6761522
关键词：
adrenergic receptor antiadrenergic agents biomechanics disease /disorder model immunocytochemistry laboratory rat neurophysiology respiratory reflex serotonin inhibitor urethra urinary catheterization urinary incontinence urinary tract disorder chemotherapy urinary tract pharmacology

项目摘要

DESCRIPTION (provided by applicant): Stress urinary incontinence (SUI) is defined as involuntary loss of urine secondary to an increase in abdominal pressure during events such as sneezing, coughing or laughing in the absence of bladder contractions. This disorder is a significant gynecological/urological problem currently affecting approximately 25 million American women. These SUI patients exhibit the high incidence of intrinsic sphincter deficiency, characterized by a malfunction of the urethral sphincter mechanism resulting in the low-pressure urethra. However, normal physiology and pathophysiology of the urethral continence mechanism in relation to SUI are not well elucidated. Thus, utilizing both in-vivo and ex-vivo techniques developed in our laboratory, we propose to perform systematic analyses of urethral continence mechanisms under stress conditions. First, in-vivo neurophysiological analyses will be performed in normal animals and animal models of SUI. Next, ex-vivo biomechanical analyses will be performed of the normal and SUI urethra. Finally, based on these results, we will also seek to explore potential pharmacotherapies of SUI. In this proposal, we hypothesize: 1) the detailed neurophysiological and biomechanical properties contributing to normal urethral continence mechanisms at different positions along the urethra can be identified in normal rats, 2) pathological changes in neurophysiological and biomechanical properties of urethral continence mechanisms can be identified in two different animals models of SUI, and 3) pharmacological treatments using serotonine/norepinephrine reuptake inhibitors and/or adrenoceptor agonists can improve urethral continence mechanisms in two animal models of SUL The Specific Aims of this grant are: I) to characterize the normal physiological and biomechanical properties of the urethral closure mechanisms in normal animals using: a) microtip transducer catheters to measure bladder and urethral responses in-vivo during sneezing or passive increases in intravesical pressure, b) in-vivo leak point pressure measurements during sneezing or passive increases in intravesical pressure, and c) ex-vivo whole urethra biomechanical studies; II) to investigate the pathological changes in the above measurements in two rat models of SUI (vaginal over distension or transection of the nerves to external urethral sphincter and pelvic floor muscles); and III) to investigate possible pharmacotherapies for improving the urethral closure mechanism in the two rat models of SUI. By defining the detailed urethral pathology of SUI, we can offer the hope of prevention and reversal of this potentially devastating condition. This is recognized as a high priority in the urologic/gynecologic care of SUI patients.

描述（由申请人提供）：压力性尿失禁（SUI）被定义为在没有膀胱收缩的情况下，在打喷嚏、咳嗽或大笑等事件期间，继发于腹压增加而导致的无意识尿液流失。这种疾病是一个严重的妇科/泌尿科问题，目前影响着大约 2500 万美国女性。这些 SUI 患者内括约肌缺陷的发生率很高，其特征是尿道括约肌机制出现故障，导致尿道低压。然而，与 SUI 相关的尿道节制机制的正常生理学和病理生理学尚未得到很好的阐明。因此，利用我们实验室开发的体内和离体技术，我们建议对压力条件下的尿道节制机制进行系统分析。首先，将在正常动物和 SUI 动物模型中进行体内神经生理学分析。接下来，将对正常尿道和 SUI 尿道进行离体生物力学分析。最后，基于这些结果，我们还将寻求探索 SUI 的潜在药物疗法。在该提议中，我们假设：1）可以在正常大鼠中识别出尿道不同位置处有助于正常尿道节制机制的详细神经生理学和生物力学特性，2）可以识别尿道节制机制的神经生理学和生物力学特性的病理变化在两种不同的 SUI 动物模型中，以及 3) 使用血清素/去甲肾上腺素再摄取抑制剂和/或肾上腺素受体进行药物治疗激动剂可以改善两种 SUL 动物模型的尿道节制机制。这项资助的具体目标是： I) 使用以下方法表征正常动物尿道闭合机制的正常生理和生物力学特性：a) 微尖传感器导管测量膀胱和尿道打喷嚏或膀胱内压力被动增加期间的体内反应，b)打喷嚏或膀胱内压力被动增加期间的体内泄漏点压力测量，以及c)离体整个尿道生物力学研究； II)研究两种SUI大鼠模型（阴道过度扩张或尿道外括约肌和盆底肌肉神经横断）上述测量的病理变化； III) 研究改善两种 SUI 大鼠模型尿道闭合机制的可能药物疗法。通过定义 SUI 的详细尿道病理学，我们可以提供预防和逆转这种潜在破坏性病症的希望。这被认为是 SUI 患者泌尿科/妇科护理中的一个高度优先事项。