Neurophysiology and Biomechanics of Urethra in SUI

SUI 尿道的神经生理学和生物力学

• 批准号: 7054143
• 负责人: NAOKI YOSHIMURA
• 金额: $ 33.47万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 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/7054143
• 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

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）：压力尿失禁（SUI）被定义为在没有膀胱收缩的情况下，诸如打喷嚏，咳嗽或笑声之类的事件中腹压增加的非自愿损失。这种疾病是目前影响约2500万美国女性的重大妇科/泌尿外科问题。这些SUI患者表现出固有括约肌缺陷的高发病率，其特征是导致低压尿道的尿道括约肌机制故障。但是，与SUI相关的尿道连续性机制的正常生理和病理生理学尚未得到很好的阐明。因此，利用实验室中开发的体内和前体内技术，我们建议在应力条件下对尿道连续性机制进行系统分析。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，将对正常和SUI尿道进行前体生物力学分析。 最后，根据这些结果，我们还将寻求探索SUI的潜在药物治疗。在该提案中，我们假设：1）详细的神经生理学和生物力学特性有助于在不同位置沿着尿道的不同位置处于正常位置的正常尿道连续性机制，可以在正常大鼠中鉴定出在两种不同动物模型中使用尿道连续性机制的神经生理学和生物力学特性的病理学变化，可鉴定出SUII的尿道连续性机制。血清素/去甲肾上腺素的再摄取抑制剂和/或肾上腺素受体激动剂可以改善两个SUL动物模型中该赠款的特定目的的尿道连续性机制：i）i）表征正常动物中尿素闭合机制的正常生理和生物力学特性，使用：a）使用以下方式：打喷嚏或被动在静脉压力下增加，b）在打喷嚏或静脉内压力中被无源增加的体内泄漏点压力测量，c）c）全体尿道生物力学研究； ii）研究两种大鼠SUI模型中上述测量的病理变化（神经的阴道延伸或向外部尿道括约肌和骨盆底肌肉的横断）； iii）研究了在SUI的两种大鼠模型中可能改善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，我们可以提供预防和逆转这种潜在毁灭性状况的希望。这被认为是SUI患者的泌尿科/妇科护理中的高度优先级。