Eberli Daniel, Andersson Karl-Erik, Yoo James J, Atala Anthony
Wake Forest Institute for Regenerative Medicine, Medical Center Boulevard, Winston-Salem, NC 27514-1094, USA.
BJU Int. 2009 Jan;103(2):248-53. doi: 10.1111/j.1464-410X.2008.08001.x. Epub 2008 Sep 8.
To develop a canine model of external urinary sphincter insufficiency by creating irreversible damage to the sphincter, because there is a need for a reliable and reproducible large animal model for the study of stress urinary incontinence (SUI) caused by deficient sphincter function.
About a quarter of the total external sphincter muscle was removed microsurgically from seven female dogs; three age-matched dogs served as normal controls. The dogs had standard urodynamic and radiographic studies before and at 1, 2, 3, 4 and 7 months after surgery. Three dogs were killed at 4 months and four at 7 months after surgery for tissue analyses.
The interventions produced a consistent outcome. Urodynamic studies showed a significant and sustained decrease in sphincter function, which included a static urethral pressure profile, stress urethral profile and detrusor leak-point pressure. Furthermore, in vivo pudendal nerve stimulation and organ-bath studies of the retrieved tissue strips confirmed the loss of sphincter tissue function. Histologically, absence of functional sphincter muscle was evident in the damaged sphincter region.
These results show that a reliable and reproducible canine model of irreversible sphincter insufficiency can be created by microsurgical removal of sphincter muscle tissue. This model of external sphincter insufficiency could be used for evaluating methods (e.g. cell therapies) for treating SUI.
通过对外括约肌造成不可逆损伤来建立犬外括约肌功能不全模型,因为需要一种可靠且可重复的大型动物模型来研究由括约肌功能不足引起的压力性尿失禁(SUI)。
通过显微手术从7只雌性犬身上切除约四分之一的外括约肌肌肉;3只年龄匹配的犬作为正常对照。这些犬在手术前以及术后1、2、3、4和7个月进行了标准的尿动力学和影像学研究。3只犬在术后4个月处死,4只在术后7个月处死以进行组织分析。
干预产生了一致的结果。尿动力学研究显示括约肌功能显著且持续下降,包括静态尿道压力分布、应激尿道压力分布和逼尿肌漏点压力。此外,对取出的组织条进行的体内阴部神经刺激和器官浴研究证实了括约肌组织功能的丧失。组织学上,在受损的括约肌区域明显缺乏功能性括约肌肌肉。
这些结果表明,通过显微手术切除括约肌肌肉组织可以建立一种可靠且可重复的不可逆括约肌功能不全犬模型。这种外括约肌功能不全模型可用于评估治疗SUI的方法(如细胞疗法)。