Periurethral Injection of Sustained Release Basic Fibroblast Growth Factor Improves Sphincteric Contractility of the Rat Urethra Denervated by Botulinum-A Toxin

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Abstract

Purpose

We evaluated the effects of sustained release basic fibroblast growth factor injection in rat urethra denervated by botulinum-A toxin (Wako Life Science, Osaka, Japan).

Materials and Methods

A total of 30 female Sprague-Dawley rats underwent periurethral injection of 10 U botulinum-A toxin to induce chemical denervation of the urethral sphincter. Leak point pressure in the waking state was determined and a significant decrease in leak point pressure vs that in control rats was confirmed (mean ± SD 58.7 ± 6.2 vs 120.7 ± 13.0 cm H2O, p <0.0001). Two weeks later 0, 50 and 200 μg basic fibroblast growth factor incorporating 200 μl gelatin hydrogels in 10 rats each were injected into the urethral sphincter, enabling sustained release of basic fibroblast growth factor for 2 weeks. Four weeks later injection leak point pressure measurement and histological evaluation of the urethra were performed.

Results

Leak point pressure in rats with 50 and 200 μg basic fibroblast growth factor injection was significantly higher than in rats with the 0 μg injection (82.7 ± 9.0 vs 95.1 ± 6.2 and 119.3 ± 8.1 cm H2O, p = 0.0021 and <0.0001, respectively). Maximum cross-sectional area of the urethral smooth muscle layer in the 50 and 200 μg groups significantly increased compared with that in the urethra in the 0 μ group, which was considered 100% (114.1% ± 15.8% and 132.5% ± 13.4%, p = 0.029 and <0.0001, respectively). Similarly the cross-sectional area of the striated sphincter in the 50 and 200 μg groups was greater than the 100% in the 0 μg group (112.3% ± 15.6% and 124.3% ± 14.1%, p = 0.069 and 0.0007, respectively). Vascular density in the urethral peri-atrophic zone in the 50 and 200 μg groups was significantly higher than in the 0 μg group (p = 0.027 and <0.0001, respectively).

Conclusions

Sustained release basic fibroblast growth factor injection in the chemically denervated urethral sphincter facilitates regeneration of the urethral muscles and improves sphincteric contractility. Endoscopic periurethral injection of basic fibroblast growth factor incorporating gelatin hydrogels may be an attractive therapy for stress urinary incontinence.

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