[Experimental study of voiding dysfunction induced by cerebral infarction in rats].

BACKGROUND

Although clinical reports concerning voiding dysfunction after cerebrovascular disease are observed, no experimental studies have been carried out using an animal model. This study was performed to establish an animal model to evaluate neurogenic voiding dysfunction associated with cerebral infarctions.

METHODS

Male Sprague-Dawley (S-D) rats weighing between 250 to 350 g were used. To induce regional cerebral infarction in rats, 4-0 monofilament nylon thread was introduced through the left internal carotid artery into the origin of the left middle cerebral artery. Cystometric examination was performed in conscious rats through a catheter chronically implanted into the bladder dome. Changes in body weight and bladder capacity were studied. The effects of intravenous oxybutynin hydrochloride, atropine and nifedipine on the conscious rat bladder were examined. By measuring the contractile response to field stimulation with added atropine and alpha, beta-methylene-ATP, the proportion of muscarinergic and purinergic innervation was compared between them.

RESULTS

Bladder capacity in cerebral infarcted rats was significantly decreased just after middle cerebral artery occlusion, and 14, 21 and 28 days after occlusion reached less than half that in sham operated and untreated rats. Bladder capacity correlated with the area of infarcted lesion determined by triphenyltetrazolium chloride staining. In the cerebral infarcted rats, bladder capacity significantly increased at low concentrations of oxybutynin hydrochloride, while in the sham operated rats bladder capacity did not increase. Although an increase in bladder capacity was observed after administration of atropine both in cerebral infarcted and sham operated rats, a significant increase of residual urine was found and considered to be caused by decreased detrusor contraction pressure. Nifedipine increased bladder capacity in the cerebral infarcted rats without increasing residual urine. There was no significant difference in the proportion of muscarinergic and purinergic innervation between the cerebral infarcted and sham operated rats.

CONCLUSION

These results indicate that calcium channel blocking agents may operate especially on the central nervous system rather than peripheral neuromuscular system, resulting in augmentation of the bladder capacity in the cerebral infarcted rats. Hitherto, the action of oxybutynin hydrochloride on the peripheral neuromuscular system is considered to be the most important, but in the cerebral infarcted rats its action on the central nervous system should also be considered. This type of animal model is believed to be useful to study neurogenic voiding dysfunction of human subjects with cerebrovascular disease.