TITLE:
Comparison of Combination Treatments of Distigmine and either Mirabegron or Solifenacin for Rats with Partial Bladder Outlet Obstruction
AUTHORS:
Kimio Sugaya, Saori Nishijima, Katsumi Kadekawa, Katsuhiko Noguchi, Katsuhiro Ashitomi, Seiji Matsumoto, Hideyuki Yamamoto
KEYWORDS:
Bladder Outlet Obstruction, Detrusor Hyperactivity with Impaired Contractility, Distigmine, Mirabegron, Solifenacin
JOURNAL NAME:
Open Journal of Urology,
Vol.12 No.6,
June
30,
2022
ABSTRACT: Objective: Detrusor hyperactivity with impaired contractility (DHIC) is not an uncommon bladder disorder, and is often difficult to treat. Therefore, using a rat model featuring both urinary frequency and residual urine, we investigated whether an anticholinergic agent (solifenacin) or a β3-agonist (mirabegron) is more suitable to combine with distigmine to treat DHIC. Methods: The partial bladder outlet obstruction (BOO) rat model was used. Rats were treated for 2 weeks: BOO/Solifenacin group was treated with 0.1 mg/kg solifenacin (n = 8), BOO/Mirabegron group was treated with 1 mg/kg mirabegron (n = 8), BOO/- group was not drug-treated but was given distilled water (n = 8), and the control group was also given distilled water (n = 8). Then the urethral ligature was removed under urethane anesthesia, and continuous cystometry was performed to evaluate bladder function. Baseline measurements were taken, then distigmine was administered to all groups, and cystometry was performed again to measure changes in bladder function. Results: Residual volumes increased in the BOO/- group, and the detrusor contractions were more frequent than that of the control group. Solifenacin treatment did not influence changes, except for threshold pressure, to any cystometric measurements. However, mirabegron treatment decreased the residual volume and residual volume rate; it also decreased detrusor contraction frequency similar to measurements obtained from the control group. Distigmine treatment enhanced detrusor contractions, which resulted in less residual volume, and decreased detrusor contraction frequency in the BOO model. Conclusions: The combination of distigmine and mirabegron was determined to be a better treatment than the combination of distigmine and solifenacin for DHIC.