ONTOGENY OF BLADDER FUNCTION

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 据估计，全国失禁费用在十亿美元左右 在一年的时间里，它是制度化的主要原因 老年人。

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.