ONTOGENY OF BLADDER FUNCTION

膀胱功能的个体发育

基本信息

批准号：
2016448
负责人：
Stephen Anthony Zderic
金额：
$ 10.84万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-01-01 至 1997-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2016448
关键词：
aging animal tissue anticholinergic agent calcium flux embryo /fetus growth /development laboratory rabbit mature animal newborn animals physiology pregnancy receptor expression smooth muscle urinary bladder disorder urinary tract motility /pressure urinary tract pharmacology

项目摘要

Vesicoureteral reflux is one of the more common disorders treated by pediatric urologists. In the past reflux was felt to be secondary to anatomic malpositioning of the ureters resulting in poor intramural tunnel length and therefore an incompetent flap valve mechanism. However many children outgrow their reflux with maturation, and the classic explanation was that the trigone also matures with growth. Reflux however has a physiologic or urodynamic component as is evidenced by numerous clinical studies documenting urodynamic abnormalities in children with reflux. One such study has shown that in neonates with high grade reflux, the voiding pressures exceeded 100 cm of H2O in 17/18 cases. The ontogeny of voiding function in normal children has not been clinically studied for ethical reasons (such studies are invasive), and thus we became interested in studying this in a laboratory model. Our preliminary data in a rabbit whole bladder model showed that the intravesical pressures that could be generated in neonatal rabbit bladders greatly exceeded those from mature animals. This work was carried over to a model using muscle strips which demonstrated that the neonatal smooth muscle was generating greater stresses in response to a variety of agonists. In further work we provided evidence that this may be in part due to differences in how free intracellular calcium rises during a stimulus induced contraction. Our evidence suggests that the neonatal rabbit bladder smooth muscle is far more dependent on extracellular calcium to generate force than its adult counterpart. The physiologic, pharmacologic, biochemical, metabolic, and histologic explanations for the differences in the ontogeny of bladder function will be the focus of this proposal. While elevated voiding pressures alone are unlikely to cause reflux, they could certainly be a contributing factor. A better understanding of bladder physiology with aging would be clinically useful to several disciplines. In addition to reflux, urologists see many children and adults with incontinence. The cost of incontinence is estimated to be in the billion dollar range nationally over a 1 year period and it is a leading cause for institutionalization of the elderly.

囊泡级反流是由小儿泌尿科医生。过去的回流被认为是次要的输尿管的解剖错位导致室内不良隧道长度，因此是无能的皮瓣机制。然而许多孩子随着成熟和经典而超越自己的回流解释说，Trigone也随着增长而成熟。回流但是，具有生理或尿动力学成分许多临床研究记录了尿动力异常回流的孩子。一项这样的研究表明，在新生儿中高级回流，空隙压力在17/18中超过100 cm的H2O 案例。正常儿童的空白功能的个体发育尚未出于道德原因进行临床研究（此类研究是侵入性的），并且因此，我们对在实验室模型中进行研究感兴趣。我们的兔子整个膀胱模型中的初步数据表明可以在新生儿兔子中产生的静脉压力膀胱大大超过了成熟动物的膀胱。这项工作是使用肌肉条延伸到模型，证明新生儿平滑肌响应于A产生更大的应力多种激动剂。在进一步的工作中，我们提供了证据表明这可能部分原因是自由细胞内钙的差异差异在刺激引起的收缩期间。我们的证据表明新生儿兔膀胱平滑肌更依赖细胞外钙比其成年对应物产生力。这生理学，药理，生化，代谢和组织学解释了膀胱功能个体发育的差异的解释成为该提议的重点。同时独自抬高空隙压力不太可能引起反流，它们当然可以是一个贡献因素。更好地了解随着衰老的膀胱生理学在临床上对几个学科有用。除了回流，泌尿科医生看到许多儿童和成人尿失禁。费用尿失禁估计在全国数十亿美元范围内在一年的时间内，这是制度化的主要原因老人。