Ambulatory and cystometric response following single versus multiple onabotulinumtoxina detrusor injections in a rat model of overactive bladder induced by intravesical acetic acid
Introduction: Intradetrusor onabotulinumtoxinA (BTX) chemo-denervation is an established therapy for appropriately selectedpatients who fail first and second-line treatments for overactive bladder. There has been much variability regarding injectionpatterns and concentration of BTX described in the literatureincluding templates which generally deliver the toxin to the posterior and lateral walls of the bladder. The physiologic effect of different injection patterns deserves further investigation. Methods: Thirty-six adult female rats were divided into six (n = 6) groups. Treatment animals received intradetrusor injection of 7.5 units (in 25 μL saline) BTX to the bladder: intact control (no injection); saline vehicle control (five aliquots); trigone (one aliquot); posterior and lateral walls (three aliquots); whole bladder (five aliquots); unilateral (one aliquot). Animals were acclimated and micturition frequency and volume were assessed using metabolic cages at baseline (day 0, 7) and following injection (day 14, 21, 28). On day 7, animals underwent detrusor injection via midline incision. On day 28, overactive bladder was inducedwith acetic acid bladder instillation (0.25%, 30-minutes). Bladder function was assessed using anesthetized cystometry before and after acid instillation. Results: All but one animal survived until final testing. One rat in the trigone group expired during recovery from anesthesia after injection. Ambulatory urinary frequency and mean voided volume show consistent trends, with stable voided volume demonstrated over timein all groups.Each animal demonstrated a consistent voiding pattern at each of the five metabolic cage time points; however there was wide variability from animal to animal. All controls developed obvious detrusor overactivity when challenged with acetic acid. In contrast, BTX resulted in increased threshold pressure immediately prior to spontaneous micturition and was successful in suppressing detrusor overactivity in treated rats that underwent instillation of acetic acid. Overall bladder contractility was preserved to a greater degree in the unilateral single aliquot injection group compared to the multiple injection treatment groups. Conclusion: With equal total toxin delivery, the various BTX injection patterns did not result in clear physiologic differences in our rat model of overactive bladder. The only exception was that unilateral single aliquot BTX injection appeared to preserve bladder contractility compared to multiple BTX injections. Funding Source: SUFU Foundatio