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

Autor: Dieter AA; From the *Department of Obstetrics and Gynecology, Duke University Medical Center, Durham; †Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill; ‡Institute for Medical Research, Durham Veterans Affairs Medical Center; §Department of Surgery, Duke University Medical Center; ∥Department of Research and Development, Durham Veterans Affairs Medical Center, Durham, NC; and ¶Department of Surgery, University of Texas Medical Branch, Galveston, TX., Wu JM, Siddiqui NY, Degoski DJ, Brooks JM, Dolber PC, Fraser MO
Jazyk: angličtina
Zdroj: Female pelvic medicine & reconstructive surgery [Female Pelvic Med Reconstr Surg] 2016 Nov/Dec; Vol. 22 (6), pp. 467-471.
DOI: 10.1097/SPV.0000000000000316
Abstrakt: 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.
Competing Interests: and Source Funding: The authors have nothing to declare..
Databáze: MEDLINE