ONTOGENY OF BLADDER FUNCTION

膀胱输尿管返流是一种较常见的疾病，可通过 儿科泌尿科医生。在过去，回流被认为是次要的 输尿管解剖错位导致壁内较差 隧道长度过长，因此襟翼阀机构不起作用。然而， 随着年龄的增长，许多孩子不再反胃，而经典的 解释是，三角区也会随着生长而成熟。回流 然而，它具有生理或尿动力学成分，这是由 大量临床研究记录了尿流动力学异常 有反流症状的儿童。一项这样的研究表明，在患有糖尿病的新生儿中 高级反流，17/18年排尿压力超过100厘米水 案子。正常儿童排尿功能的个体发育尚未得到证实 出于伦理原因进行临床研究(此类研究是侵入性的)，以及 因此，我们开始对在实验室模型中研究这一问题感兴趣。我们的 兔全膀胱模型的初步数据显示， 新生兔可产生的膀胱内压 膀胱的数量远远超过成年动物的膀胱。这项工作是 通过使用肌肉条的模型来证明 新生儿的平滑肌产生更大的压力 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 部分原因是细胞内游离钙升高的方式不同 在刺激引起的收缩过程中。我们的证据表明 新生兔膀胱平滑肌更依赖于 细胞外钙产生的力量比它的成年对应物。这个 生理学、药理学、生化、代谢学和组织学 对膀胱功能个体发育差异的解释将 成为这项提案的重点。当排尿压力升高时 不太可能导致反流，它们肯定会对 因素。对随年龄增长的膀胱生理学有更好的了解 对几个学科有临床应用价值。除了回流， 泌尿科医生发现许多儿童和成人患有大小便失禁。的成本 据估计，全国范围内的大小便失禁在10亿美元左右。 超过1年，是制度化的主要原因 关于老年人的。

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.