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Comparison of Combination Treatments of Distigmine and either Mirabegron or Solifenacin for Rats with Partial Bladder Outlet Obstruction

Comparison of Combination Treatments of Distigmine and either Mirabegron or Solifenacin for Rats with Partial Bladder Outlet Obstruction
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摘要 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. 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.
作者 Kimio Sugaya Saori Nishijima Katsumi Kadekawa Katsuhiko Noguchi Katsuhiro Ashitomi Seiji Matsumoto Hideyuki Yamamoto Kimio Sugaya;Saori Nishijima;Katsumi Kadekawa;Katsuhiko Noguchi;Katsuhiro Ashitomi;Seiji Matsumoto;Hideyuki Yamamoto(Southern Knights’ Laboratory, Okinawa, Japan;Center for Advanced Research and Education, Asahikawa Medical University, Asahikawa, Japan;Department of Biochemistry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan)
出处 《Open Journal of Urology》 2022年第6期366-375,共10页 泌尿学期刊(英文)
关键词 Bladder Outlet Obstruction Detrusor Hyperactivity with Impaired Contractility Distigmine MIRABEGRON SOLIFENACIN Bladder Outlet Obstruction Detrusor Hyperactivity with Impaired Contractility Distigmine Mirabegron Solifenacin
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