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Characterizing the Bladder's Response to Onabotulinum Toxin Type A Using a Rat Model.

Publication ,  Journal Article
Dieter, AA; Wu, JM; Siddiqui, NY; Degoski, DJ; Brooks, JM; Dolber, PC; Fraser, MO
Published in: Female Pelvic Med Reconstr Surg
2016

OBJECTIVES: The aim of this study was to characterize the response of the rat bladder neuromuscular system to intramural injection of onabotulinum toxin type A (BoNT/A) over 9 weeks using in vivo cystometry (CMG) and in vitro contractility (IVC). METHODS: Chronic bladder catheters were implanted in female Sprague-Dawley rats, and either (1) BoNT/A (10 units in 20 μL saline) or (2) saline (20 μL) was injected in 5 × 4 μL doses throughout the bladder wall. At 1, 3, 6, and 9 weeks after injection, conscious restrained CMG was performed. At each time point, 25% of each group (8 BoNT/A and 4 controls) was euthanized and bladders harvested for IVC. We measured IVC in response to electric field stimulation, carbachol, and potassium chloride. RESULTS: In total, 47 animals were included; 31 underwent BoNT/A injection, and 16 received sham (saline). Bladder capacities did not differ significantly between groups for each time point. One week after injection BoNT/A animals exhibited significantly longer bladder contraction durations and lower voiding efficiencies compared with controls. By 3 weeks these values returned to control levels. For BoNT/A animals, contractile response to carbachol stimulation was enhanced at 3 weeks. Otherwise, there were no differences in IVC responses. CONCLUSIONS: One week after BoNT/A injection, prolonged bladder contractions are noted in rats. This may reflect supraspinal compensation for denervation by increasing the duration of efferent drive during voiding. After 3 weeks postinjection, we observed no differences in either CMG or IVC responses suggesting either compensatory efferent sprouting, increased gap junction formation, or loss of BoNT/A effect.

Duke Scholars

Published In

Female Pelvic Med Reconstr Surg

DOI

EISSN

2154-4212

Publication Date

2016

Volume

22

Issue

6

Start / End Page

467 / 471

Location

United States

Related Subject Headings

  • Urinary Catheterization
  • Urinary Bladder
  • Rats, Sprague-Dawley
  • Potassium Chloride
  • Neuromuscular Agents
  • Muscle Contraction
  • Gap Junctions
  • Female
  • Electric Stimulation
  • Dose-Response Relationship, Drug
 

Citation

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Dieter, A. A., Wu, J. M., Siddiqui, N. Y., Degoski, D. J., Brooks, J. M., Dolber, P. C., & Fraser, M. O. (2016). Characterizing the Bladder's Response to Onabotulinum Toxin Type A Using a Rat Model. Female Pelvic Med Reconstr Surg, 22(6), 467–471. https://doi.org/10.1097/SPV.0000000000000316
Dieter, Alexis A., Jennifer M. Wu, Nazema Y. Siddiqui, Danielle J. Degoski, Jillene M. Brooks, Paul C. Dolber, and Matthew O. Fraser. “Characterizing the Bladder's Response to Onabotulinum Toxin Type A Using a Rat Model.Female Pelvic Med Reconstr Surg 22, no. 6 (2016): 467–71. https://doi.org/10.1097/SPV.0000000000000316.
Dieter AA, Wu JM, Siddiqui NY, Degoski DJ, Brooks JM, Dolber PC, et al. Characterizing the Bladder's Response to Onabotulinum Toxin Type A Using a Rat Model. Female Pelvic Med Reconstr Surg. 2016;22(6):467–71.
Dieter, Alexis A., et al. “Characterizing the Bladder's Response to Onabotulinum Toxin Type A Using a Rat Model.Female Pelvic Med Reconstr Surg, vol. 22, no. 6, 2016, pp. 467–71. Pubmed, doi:10.1097/SPV.0000000000000316.
Dieter AA, Wu JM, Siddiqui NY, Degoski DJ, Brooks JM, Dolber PC, Fraser MO. Characterizing the Bladder's Response to Onabotulinum Toxin Type A Using a Rat Model. Female Pelvic Med Reconstr Surg. 2016;22(6):467–471.

Published In

Female Pelvic Med Reconstr Surg

DOI

EISSN

2154-4212

Publication Date

2016

Volume

22

Issue

6

Start / End Page

467 / 471

Location

United States

Related Subject Headings

  • Urinary Catheterization
  • Urinary Bladder
  • Rats, Sprague-Dawley
  • Potassium Chloride
  • Neuromuscular Agents
  • Muscle Contraction
  • Gap Junctions
  • Female
  • Electric Stimulation
  • Dose-Response Relationship, Drug