Novel Applications of Sarcomere Length to Improve Anal Continence

描述(由申请人提供)： 这项建议的总体目标是提高女性退伍军人患者的生活质量。最近的调查表明，女性患者构成了VA医疗保健用户中增长最快的部分，盆底疾病(大小便失禁、盆腔器官脱垂)在这一患者群体中非常常见。据报道，60岁以上的女性中约有7%-10%的人出现大便失禁。与分娩相关的损伤/与肛门外括约肌损伤有关的创伤(EAS)被认为是导致大便失禁的最常见原因。最常见的治疗大便失禁的外科手术是重叠括约肌成形术，长期的随访研究表明，这种手术矫正的成功率很低。我们计划使用动物模型来研究EAS的长度张力特性，然后进行一系列实验，以表明这些知识可以用于增强肛管压力和控制功能。我们的初步数据显示，体内可操作的EAS肌节长度远小于其最佳长度，通过增加EAS肌节长度来获得EAS肌肉功能是可能的。本研究的具体目标是：1)在动物模型(兔)中，确定手术折叠术对EAS肌节长度和肛管压力的影响。我们还将确定EAS植入术对EAS肌肉功能增益耐久性的长期影响。2)我们还将研究以下几个方面，以了解为什么括约肌成形术不能提供长期的效果。在我们的动物模型(兔)中，这些研究的目标将是确定：a)EAS肌切开术对大便失禁发展的影响。B)EAS肌切开术对肌节长度的影响c)不同重叠程度的括约肌成形术对EAS肌功能的影响。3)人EAS肌的长度张力关系，表明兔和人的长度张力特性相似。 公共卫生相关性： 这项提议的总体目标是改善女性退伍军人患者的生活质量。军队中女性人数的增加正在重塑退伍军人群体，女性现在构成了符合条件的退伍军人医疗保健用户中增长最快的部分。为了认识到妇女的保健需求，退伍军人事务部于2004年主办了第一次全国退伍军人健康研究议程制定会议，以确定研究的优先事项，以满足退伍军人的需要。尿失禁和大便失禁影响大量妇女(高达20%或更多)。因此，对大便失禁和大便失禁的基础性和翻译性研究对于军队中的女性和合格的退伍军人保健使用者来说是至关重要的。大便失禁是一种主要的内科疾病，尤其是在女性中，因为与出生有关的肛门括约肌损伤。我们研究的目标是提高我们对肛门括约肌生理学的理解。我们认为，新的信息将导致更好的内科和外科治疗策略，以治疗大便失禁。本方案中讨论的生理学原理很可能适用于尿失禁和失禁功能。我们的观察表明，就像肛门外括约肌一样，其他括约肌，包括那些涉及尿失禁的肌肉，与本提案中讨论的相似的生理原理。

DESCRIPTION (provided by applicant): ABSTRACT The overall objective of this proposal is to improve the quality of life of female Veteran patient population. Recent surveys indicate that the female patient population constitutes the fastest growing segment of VA health care users and pelvic floor disorders (fecal and urinary incontinence, pelvic organ prolapse) are extremely common in this patient population. Fecal incontinence is reported approximately, 7-10% of women over the age of 60. Child birth related injury/ trauma to external anal sphincter injury (EAS) is attributed as the most common cause of fecal incontinence. The most commonly performed surgical procedure for the treatment of fecal incontinence is overlapping sphincteroplasty and long term follow up studies show a poor success rate with this surgical correction. We plan to use an animal model to study the length tension properties of the EAS, and then perform a series of experiments to show that this knowledge can be used to enhance anal canal pressure and continence function. Our preliminary data show that the in-vivo operational EAS muscle sarcomere length is much smaller than its optimal length and it is possible to gain EAS muscle function by increasing the EAS sarcomere length. The specific goals of our study are: 1) To determine the effects of surgical plication of the EAS on the EAS sarcomere length and the anal canal pressure in-vivo in an animal model (rabbit). We will also determine the long-term effects of EAS plication on the durability of gain in the EAS muscle function. 2) We will also study the following to understand why sphincteroplasty operation does not provide the long lasting effects. The goals of these studies in our animal model (rabbit) will be to determine: a) The effects of the EAS myotomy on the development of fecal incontinence. b) The effect of EAS myotomy on the sarcomere length c) The effects of sphincteroplasty with varying degrees of overlap on the EAS muscle function. 3) The length tension relationship of the EAS muscle in the humans to show that the length tension properties of the rabbit and humans are similar. PUBLIC HEALTH RELEVANCE: The overall objective of this proposal is to improve the quality of life of the female Veteran patient population. The expansion of women in the military is reshaping the veteran population, with women now constituting the fastest growing segment of eligible VA health care users. In recognition of the health care needs of women, the VA Office of Research & Development sponsored the first national VA Women's Health Research Agenda-setting conference to map research priorities to the needs of women veterans in 2004. Urinary and fecal incontinence affect large number of women (up to 20% or more). Therefore, the fundamental and translational research into fecal continence and incontinence is of utmost importance to the women in military and eligible VA health care users. Fecal incontinence is a major medical illness, especially in women because of the birth related injury to the anal sphincters. The goals of our study are to improve our understanding of the physiology of anal sphincter muscles. We propose that the new information will lead to better medical and surgical treatment strategies in the treatment of fecal incontinence. The physiological principles discussed in this proposal are quite likely to be applicable to urinary continence and incontinence function. Our observations suggest that just like external anal sphincter, the other sphincter muscles, including the ones involved in urinary continence, share similar physiological principles as discussed in this proposal.