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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.

膀胱输尿管反流是一种较常见的疾病，儿科泌尿科医生在过去，反流被认为是次要的输尿管的解剖错位导致壁内不良隧道长度和因此不合格的瓣阀机构。然而许多孩子随着成熟而长大，解释是三角区也随着生长而成熟。回流然而具有生理或尿动力学成分，大量临床研究记录了儿童反流一项这样的研究表明，高度返流，17/18例排尿压力超过100 cm H2O 例正常儿童排尿功能的个体发育尚未被证实。出于伦理原因进行的临床研究（此类研究是侵入性的），以及因此我们开始有兴趣在实验室模型中进行研究。我们兔全膀胱模型的初步数据显示，新生兔膀胱内压膀胱大大超过那些从成熟的动物。这项工作是转移到使用肌肉条的模型中，该模型表明，新生儿平滑肌产生更大的应力，各种激动剂。在进一步的研究中，我们提供了证据，表明这可能部分原因是细胞内游离钙升高的方式不同在刺激引起的收缩期间。我们的证据表明新生兔膀胱平滑肌更依赖细胞外钙产生的力量比成年人。的生理学、药理学、生物化学、代谢和组织学对膀胱功能个体发育差异的解释将成为这项提案的重点。排尿压力升高不太可能引起反流，它们肯定是一种贡献，因子随着年龄的增长，更好地了解膀胱生理学将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失禁。的成本尿失禁估计在全国范围内在十亿美元的范围内在一年的时间里，它是制度化的主要原因老年人。