Delayed Treatment With Low-intensity Extracorporeal Shock Wave Therapy in an Irreversible Rat Model of Stress Urinary Incontinence.

OBJECTIVE: To determine the outcomes and mechanisms of delayed low-intensity extracorporeal shock wave therapy (Li-ESWT) in a rat model of irreversible stress urinary incontinence (SUI). MATERIALS AND METHODS: Twenty-four female Sprague-Dawley rats were randomly assigned into 3 groups: sham control, vaginal balloon dilation + ß-aminopropionitrile (BAPN; SUI group), and vaginal balloon dilation + BAPN + treatment with Li-ESWT (SUI-Li-ESWT group). An irreversible SUI model was developed by inhibiting the urethral structural recovery with BAPN daily for 5 weeks. Thereafter, in the SUI-Li-ESWT group, Li-ESWT was administered twice per week for 2 weeks. After a 1-week washout, all 24 rats were evaluated with functional and histologic studies at 17 weeks of age. Endogenous progenitor cells were detected via the EdU-labeling method. RESULTS: Functional analysis with leak point pressure testing showed that the SUI-Li-ESWT group had significantly higher leak point pressures compared with untreated rats. Increased urethral and vaginal smooth and striated muscle content and increased thickness of the vaginal wall were noted in the SUI-Li-ESWT group. The SUI group had significantly decreased neuronal nitric oxide /tyrosine hydroxylase positive nerves ratio in the smooth muscle layers of the urethra, while the SUI-Li-ESWT group had neuronal nitric oxide/tyrosine hydroxylase+ nerves ratio similar to that of the control group. The continuality of urothelial cell lining was also improved in the SUI-Li-ESWT group. In addition, there were significantly increased EdU-positive cells in the SUI-Li-ESWT group. CONCLUSION: Li-ESWT appears to increase smooth muscle content in the urethra and the vagina, increase the thickness of urethral wall, improve striated muscle content and neuromuscular junctions, restore the integrity of the urothelium, and increase the number of EdU-retaining progenitor cells in the urethral wall.

Treatment of stress urinary incontinence with low-intensity extracorporeal shock wave therapy in a vaginal balloon dilation induced rat model.

BACKGROUND: To investigate the outcomes and mechanisms of low-intensity extracorporeal shock wave therapy (Li-ESWT) on stress urinary incontinence (SUI) in a vaginal balloon dilation (VBD) rat model. METHODS: Thirty Sprague-Dawley rats were randomly grouped into normal controls, VBD only, and VBD with Li-ESWT. Li-ESWT was administered twice per week for 3 weeks. Afterward, all 30 rats were assessed with functional and histological studies. To explore the acute effect of Li-ESWT, another 25 rats, given intraperitoneal 5-ethynyl-2-deoxyuridine (EdU) at birth, were treated with Li-ESWT followed by assessment of vascular endothelial growth factor (VEGF) expression and endogenous progenitor cells distribution at 24 hours or 1 week after the last Li-ESWT therapy. Additionally, rat myoblast L6 cells were used for myotube formation assay in vitro. RESULTS: Functional analysis with leak-point pressure (LPP) testing showed that rats treated with Li-ESWT following VBD had significantly higher LPP relative to those receiving VBD only (44.8±3.2 versus 27.0±2.9 cmH2O, P<0.01). Histological examinations showed increased urethral sphincter regeneration in Li-ESWT group. The rats treated with Li-ESWT also had increased vascularity, which was confirmed by immunohistochemistry of rat endothelial cell antigen, while reverse-transcriptase polymerase chain reaction (RT-PCR) showed VEGF expression was significantly enhanced. Additionally, there were significantly increased EdU+ cells in Li-ESWT treated rats at 24 hours. In vitro, Li-ESWT promoted myotube formation from L6 cells. CONCLUSIONS: Li-ESWT ameliorated SUI by promoting angiogenesis, progenitor cell recruitment, and urethral sphincter regeneration in a rat model induced by VBD. Li-ESWT represents a potential novel non-invasive therapy for SUI.