The Effect of Oxybutynin on Structural Changes of the Obstructed Guinea Pig Bladder

Purpose: Oxybutynin is used clinically to lower intravesical pressure and detrusor overactivity. In vitro it inhibits stretch induced bladder smooth muscle cell proliferation. We tested whether oxybutynin also prevents hypertrophic bladder changes in vivo in a model of partial bladder obstruction. Materials and Methods: Subvesical obstruction was induced in immature guinea pigs by a silver ring around the urethra. Eight animals received 0.4 mg oxybutynin per kg body weight per day in 2 doses. Control groups were obstructed without oxybutynin treatment or sham operated. Urodynamic pressure flow studies were performed at 1-week intervals for 10 weeks in all animals under anesthesia with ketamine/xylazine. After 10 weeks the animals were sacrificed and the bladder was removed for structural analysis with periodic acid-Schiff stain, in which the number of glycogen granules was also scored as a measure of previous ischemia. Results: Compared to the sham treated group obstructed animals had significantly higher intravesical pressure and detrusor overactivity, lower compliance and increased contractility. Obstructed animals that received oxybutynin retained normal intravesical pressure, detrusor overactivity and compliance. Their bladder contractility increased as in obstructed animals. The oxybutynin group showed less collagen infiltration in the detrusor and fewer glycogen granules compared to those in obstructed animals. Conclusions: Our results demonstrate that oxybutynin has a protective effect on bladder function and structure. Prevention of hypertrophic and ischemic bladder changes is an argument for an early start of oxybutynin treatment in children with inborn neurogenic bladder dysfunction, such as spina bifida, or in patients with urethral valves.

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