Long-Term Effect of Ovariectomy and Simulated Birth Trauma on the Lower Urinary Tract of Female Rats

Resplande, Júlio; Gholami, Shahram S.; Graziottin, Túlio M.; ROGERS, RODMAN; Lin, Chen; Leng, Wendy W.J. de; Lue, Tom F.

doi:10.1016/s0022-5347(05)64915-4

Cited by 62 publications

(47 citation statements)

References 20 publications

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“…The measurement of threshold pressure (TP) was determined during cystometric examination as previously described (16,19). It is defined as the difference between the bladder pressure immediately before micturition and the baseline pressure at the beginning of the saline infusion.…”

Section: Methodsmentioning

confidence: 99%

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New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency

Rodríguez¹,

Chen²,

Jack³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Rodríguez, Larissa V., Shinhong Chen, Gregory S. Jack, Fernando de Almeida, Kyo Won Lee, and Rong Zhang. New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency. Am J Physiol Regul Integr Comp Physiol 288: R1332-R1338, 2005. First published January 13, 2005; doi:10.1152/ajpregu.00760.2004.-Existing animal models of stress urinary incontinence (SUI) are limited because of the low rate of incontinence seen in the animals and to their relatively low durability. In addition, most methods described to measure incontinence are operator-dependent. The aim of this study was to develop a new durable animal model of SUI and establish objective measures to quantify SUI. We subjected female rats to transabdominal urethrolysis. At baseline and at 1,4,8,12, and 24 wk after intervention, animals underwent cystometry and evaluation with abdominal leak point pressure (ALPP). Urethral resistance was evaluated by retrograde urethral perfusion pressure (RUPP). Tissues were obtained for histology and immunohistochemistry. Normal female rats had an average ALPP of 19.4 cmH2O and RUPP of 22.6 cmH2O at baseline. More than 93% of the animals had significantly decreased ALPP and RUPP after the procedure. The mean ALPP and RUPP decreased to 9.8 cmH2O and 11.2 cmH2O, respectively, by 1 wk after urethrolysis. These changes were maintained for up to 24 wk. Changes seen in urethral resistance and ALPP appear to be mediated by apoptosis, decreased neuronal mass, and smooth muscle atrophy. These results indicate that transabdominal urethrolysis is a reliable method of achieving durable decreased urethral resistance in a SUI model. RUPP and ALPP are objective and reproducible methods of assessing urethral resistance. Changes in continence and urethral resistance appear to be mediated by denervation and smooth muscle atrophy, which are seen in both elderly incontinent patients and in patients with intrinsic sphincter dysfunction. stress incontinence; abdominal leak point pressure; retrograde perfusion; urethral resistance URINARY INCONTINENCE AFFECTS 13 million Americans, the vast majority of whom (85%) are women. In 1995, the annual cost of incontinence in the United States was estimated to be $26.3 billion (26). This represents a 92% increase from the 1984 cost, and it is expected to increase due to the aging population (9). Approximately 50% of all incontinent women are classified as having stress incontinence (5, 8). The pathophysiology of stress urinary incontinence (SUI) is multifactorial and poorly understood but appears to be in part due to anatomic changes in urethral support and dysfunction of the intrinsic sphincteric mechanism of the urethra resulting in involuntary urine loss during any activity that causes abdominal straining. Given that the list of such activities includes everyday occurrences like coughing, laughing, and sneezing, SUI has an enormous impact on quality of life. In the elderly, other factors also appear to contribute to the development of an i...

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Section: Methodsmentioning

confidence: 99%

“…In the past few years, some useful rat animal models have been proposed such as simulating birth trauma with intravaginal balloon inflation (1,4,15), vaginal distension, and ovariectomy (12,19), pudendal nerve crush (4,7,10), spinal cord injury (21,28), and electrocauterization (2,27). These important investigations have shed light on the pathogenesis of SUI.…”

mentioning

confidence: 99%

New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency

Rodríguez¹,

Chen²,

Jack³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Resplande et al used the same technique of vaginal distention in immediately postpartum rats using an 18Fr catheter inflated to 5 ml for 4 hours. 22 Cannon et al performed predilation of the vagina by inserting increasing sizes (24Fr to 32Fr) of urethral dilators to accommodate the vagina of virgin rats, followed by VD using 10Fr catheters inflated to 3 ml. 24…”

Section: Models Simulating Maternal Childbirth Injuriesmentioning

confidence: 99%

Animal Models of Female Stress Urinary Incontinence

et al. 2008

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Purpose-Urinary incontinence affects 40% of women in the United States and stress urinary incontinence accounts for a large portion of affected patients. As defined by the International Continence Society, stress urinary incontinence is the involuntary leakage of urine upon effort, exertion, sneezing or coughing. Since the ultimate success of long-term management for any condition is based on an understanding of its pathophysiology, and because the pathophysiology of stress urinary incontinence is incompletely defined, animal models have recently been developed to better understand stress urinary incontinence and develop novel treatment alternatives.Materials and Methods-Several animal models for urethral dysfunction have emerged in the last few years, including those based on pathophysiological theories of urethral sphincter dysfunction that were designed to simulate maternal birth trauma. Other models have focused on the creation of a durable model of dysfunction for investigating novel treatments.Results-Since animals cannot express intent, these animal models have focused on measuring decreased urethral resistance. The most widely used methods are the sneeze test, the tilt table technique and the leak point pressure test. Newer techniques include abdominal leak point pressure, urethral pressure measurement and retrograde urethral perfusion pressure. In addition to the advantages and disadvantages of each technique, all methods measure the composite contribution to urethral resistance from smooth and striated muscle, urethral closure and connective tissue, although none measures intent.Conclusions-We critically reviewed the different models of stress urinary incontinence and urethral dysfunction as well as the different methods of measuring urethral resistance. Keywords urethra; urinary incontinence; stress; female; urodynamics; models; animal Urinary incontinence affects 40% of women in the United States. SUI, the involuntary leakage of urine upon effort, exertion, sneezing or coughing, accounts for a large portion of affected patients. More than 165,000 surgical procedures are performed for SUI in the United States. It is estimated that a third of the procedures that are performed to treat SUI are done in patients with recurrent disease. These currently performed procedures for SUI are based on compensatory and nonphysiological mechanisms. Since the ultimate success of the long-term management of any condition is based on an understanding of its pathophysiology, and because †Correspondence:

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“…Pelvic adhesions, however, were not observed at dissection. Resplande et al (22) studied the vaginal walls of rats after distention injury and found marked vaginal mucosal atrophy, an increase in collagen content, and a decrease in the muscular layer. The vaginal specimens also were contracted, appearing with many folds in the subepithelial layer (22).…”

Section: Discussionmentioning

confidence: 99%

“…Resplande et al (22) studied the vaginal walls of rats after distention injury and found marked vaginal mucosal atrophy, an increase in collagen content, and a decrease in the muscular layer. The vaginal specimens also were contracted, appearing with many folds in the subepithelial layer (22). This increased collagen content between stromal cells of the vaginal wall perhaps protects the vagina from progression to its most severe degree of decensus.…”

Section: Discussionmentioning

confidence: 99%

Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse

Rahn¹,

Acevedo²,

Word³

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Rahn DD, Acevedo JF, Word RA. Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse. Am J Physiol Regul Integr Comp Physiol 295: R1351-R1358, 2008. First published July 16, 2008 doi:10.1152/ajpregu.90447.2008 activity is increased in the postpartum vagina of wild-type (WT) animals. This degradative activity is also accompanied by a burst in elastic fiber synthesis and assembly. The mechanisms that precipitate these changes are unclear. The goals of this study were to determine how vaginal distention (such as in parturition) affects elastic fiber homeostasis in the vaginal wall and the potential significance of these changes in the pathogenesis of pelvic organ prolapse. Vaginal distention with a balloon simulating parturition resulted in increased MMP-2 and MMP-9 activity in the vaginal wall of nonpregnant and pregnant animals. This was accompanied by visible fragmented and disrupted elastic fibers in the vaginal wall. In nonpregnant animals, the abundant amounts of tropoelastin and fibulin-5 in the vagina were not increased further by distention. In contrast, in pregnant animals, the suppressed levels of both proteins were increased 3-fold after vaginal distention. Distention performed in fibulin-5-deficient (Fbln5 Ϫ/Ϫ ) mice with defective elastic fiber synthesis and assembly induced accelerated pelvic organ prolapse, which never recovered. We conclude that, in pregnant mice, vaginal distention results in increased protease activity in the vaginal wall but also increased synthesis of proteins important for elastic fiber assembly. Distention may thereby contribute to the burst of elastic fiber synthesis in the postpartum vagina. The finding that distention results in accelerated pelvic organ prolapse in Fbln5 Ϫ/Ϫ animals, but not in WT, indicates that elastic fiber synthesis is crucial for recovery of the vaginal wall from distention-induced increases in vaginal protease activity. childbirth trauma; MMP9; protease; pregnancy PELVIC ORGAN PROLAPSE IS A common problem for women with significant psychological, social, and financial implications (12,26,29). Whereas many factors appear to incite or promote the progression of prolapse, the two major risk factors for pelvic organ prolapse are history of vaginal delivery and aging. Although cesarean delivery does not completely protect the pelvic floor from the adverse effects of pregnancy, it is universally agreed that vaginal delivery has a deleterious impact on the development of pelvic organ prolapse in women, and this impact may not be of clinical significance until decades after delivery. The mechanisms by which childbirth leads to failure of pelvic organ support, however, are not well understood (3,26).Mice with null mutations in genes encoding lysyl oxidase like 1 (LOXL1) (15, 16) or fibulin-5 (FBLN5) (11) develop pelvic organ prolapse. Since both proteins play important roles in elastic fiber synthesis and assembly (19,30), these findings indicate that fa...

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Long-Term Effect of Ovariectomy and Simulated Birth Trauma on the Lower Urinary Tract of Female Rats

Cited by 62 publications

References 20 publications

New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency

New objective measures to quantify stress urinary incontinence in a novel durable animal model of intrinsic sphincter deficiency

Animal Models of Female Stress Urinary Incontinence

Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse

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