Yoshiyuki Ishiura

CHANGE IN BLADDER CONTRACTILITY ASSOCIATED WITH BLADDER OVERACTIVITY IN RATS WITH CEREBRAL INFARCTION

PURPOSE To evaluate the contractile properties of overactive bladder from rats in the chronic stage of experimental cerebral infarction. MATERIALS AND METHODS Cystometry was performed in conscious male S-D rats after inducing occlusion of the left middle cerebral artery. Bladder muscle strips were evaluated for force development in response to field stimulation, acetylcholine and KCl. By measuring the contractile response to field stimulation after adding atropine and alpha,beta-methylene-ATP, contributions of cholinergic and purinergic transmission were determined. RESULTS Bladder capacity of cerebral-infarcted rats was <50% of the capacity of sham-operated rats and significantly less than that of sham-operated rats even 4 months after surgery. There was no significant difference in bladder weight between sham-operated rats and cerebral-infarcted rats. No differences in the contractile response of detrusor strips to field stimulation and acetylcholine, or in the relative contribution of cholinergic and purinergic transmission to the contractile response, were observed over time or between strips from sham-operated rats and cerebral-infarcted rats. KCl induced significantly less contraction in strips from 4 month infarcted rats than in strips from 4 month sham-operated rats, 2 week infarcted rats and 2 month infarcted rats. CONCLUSIONS This animal model will be useful for chronic studies on the mechanism of detrusor hyperactivity (DH).

EFFECTS OF MK-801 ON BLADDER OVERACTIVITY IN RATS WITH CEREBRAL INFARCTION

PURPOSE Our objective was to evaluate the underlying mechanisms of neurogenic voiding dysfunction following cerebral infarction. MATERIALS AND METHODS The left middle cerebral artery (MCA) was occluded using 4-0 monofilament nylon thread in male S-D rats. Cystometric examination was performed in unanesthetized and urethane-anesthetized rats through a catheter chronically implanted in the dome of the bladder. RESULTS Bladder capacity of unanesthetized or urethane anesthetized rats was significantly reduced just after occlusion of the left MCA; 2 weeks after the occlusion, the capacity was less than half that in sham-operated rats. Intravenous administration of N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 to the unanesthetized sham-operated rats led to a marked dose-dependent decrease in bladder capacity. Its administration to unanesthetized rats with cerebral infarction resulted in a slight decrease in bladder capacity. In the urethane-anesthetized state, the bladder capacity of the rats with cerebral infarction was significantly increased by MK-801, 0.1 mg./kg., without inhibiting the contraction pressure or increasing the amount of residual urine. A high dose (1 mg./kg.) of MK-801 was required to increase the bladder capacity of sham-operated rats. This led to an inhibition of contraction pressure and an increase in residual urine. CONCLUSION Results in urethane anesthetized rats indicate that NMDA glutamatergic transmission is important in the overactivity of the bladder following a cerebral infarction. This model is useful in studying the neurogenic voiding dysfunction observed in patients with cerebrovascular disease.

Urodynamic Effects of Intravesical Instillation of Lidocaine in Patients With Overactive Detrusor

PURPOSE We evaluated the effects of intravesical administration of lidocaine on the overactive detrusor in patients with spinal cord injury and cerebrovascular disease. MATERIALS AND METHODS Cystometry was performed before and 15 minutes after intravesical instillation of 20 ml. of 1 and/or 4% lidocaine in 48 patients with spinal cord injury and 67 with cerebrovascular disease. RESULTS A significant increase in bladder capacity was observed following administration of 1 and 4% lidocaine in patients tested longer than 1 year after spinal cord injury. However, no significant increase was noted even with 4% lidocaine in those tested within 1 year after injury. A significant increase in bladder capacity was observed in patients with cerebrovascular disease with 4 but not 1% lidocaine. When comparing the percent increase in bladder capacity obtained with 4% lidocaine in the 2 groups, patients with spinal cord injury showed a significantly greater increase than those with cerebrovascular disease (91.6 versus 31.9%, respectively). Detrusor contractions disappeared in 37.5 versus 5.4% of patients, respectively. CONCLUSIONS Intravesical administration of lidocaine appears to be useful in differentiating detrusor hyperactivity caused by lesions of the spinal cord versus those of the brain.

Urodynamic effects of intravesical oxybutynin chloride in conscious rats.

PURPOSE To examine the factors of intravesical oxybutynin influencing the cystometrogram in normal conscious rats at various pH levels and concentrations of oxybutynin. MATERIALS AND METHODS A cystostomy catheter was implanted into the bladders of male Sprague-Dawley rats. We compared the urodynamic effects of intravesical oxybutynin dissolved in pH 4.44, 6.44 and 8.44 buffer. Two concentrations of oxybutynin solution were adopted, 0.06 and 0.6 mg./ml., and were dissolved in each pH buffer. RESULTS Although a 26% increase in bladder capacity was recognized 1 hour after instillation of pH 8.44, 0.06 mg./ml. oxybutynin, no significant difference was found in comparison with control rats. At the concentration of 0.6 mg./ml., bladder capacity markedly decreased 30 minutes to 1 hour after instillation even at pH 6.44 and 8.44. Significant decreases in detrusor contraction pressure were recognized 30 minutes to 1 hour after instillation. However, there were no significant differences among the 3 pH oxybutynin solutions. Compared with preinstillation values, significant increases in residual urine rates were observed in all pH oxybutynin solutions. Furthermore, the residual urine rate after instillation of pH 8.44 oxybutynin solution differed significantly from that of pH 4.44 oxybutynin. CONCLUSION Our results demonstrate that pH and concentration of intravesical oxybutynin solution may play an important role in relaxation of the bladder. A high concentration of oxybutynin is considered irritating to the bladder mucosa.

Morphological and Functional Factors Predicting Bladder Deterioration After Spinal Cord Injury

PURPOSE We investigated factors predictive of morphological and functional deterioration of the bladder in patients with spinal cord injury. MATERIALS AND METHODS Urological evaluation, including excretory urography and urodynamic studies, was performed once a year in 66 patients. Bladder compliance was used as an index of bladder function. RESULTS Mean age of the patients with worsening bladder form and function was significantly greater than that of those with no change. In patients with worsening bladder function intermittent catheterization was performed less frequently and mean catheterization volume was greater compared to those with improvement and no change. Catheterization was less frequent and at long intervals in patients with a high urethral closure pressure. CONCLUSIONS High storage pressure due to a high urethral closure pressure is believed to cause deterioration of bladder form and function.

Endoscopic Treatment of Vesicoureteral Reflux in Patients With Myelodysplasia

PURPOSE We assessed the usefulness of and indications for endoscopic treatment of vesicoureteral reflux in myelodysplasia patients. MATERIALS AND METHODS A total of 26 patients treated with intermittent catheterization was divided into 11 (16 ureters) with and 15 without vesicoureteral reflux. In 9 patients (13 ureters) endoscopic correction was performed with 3% atelo-collagen and without anesthesia at the outpatient clinic. In each ureter we obtained the sum of scores for 4 risk factors for upper urinary tract deterioration: bladder compliance less than 10 ml./cm. water, grade 2 to 3 bladder deformity, detrusor-sphincter dyssynergia and urethral closure pressure 50 cm. water or greater. RESULTS No reflux was demonstrated immediately after the initial collagen injection but cystography 3 to 6 months later showed recurrent reflux in 5 ureters (38%). Repeat injection cured the reflux, with results persisting for an average of 17 months. Mean risk factor score for patients without vesicoureteral reflux was significantly lower than that for patients with reflux. In patients treated with intermittent catheterization and anticholinergic agents the mean score for ureters with an increased or unchanged reflux grade was significantly greater than for those with a decreased grade. CONCLUSIONS Endoscopic treatment of reflux appears to be safe and useful in patients with myelodysplasia. The treatment is preferable in those with high risk factor scores due to the possibility of increased reflux grade in such patients.

Single Ectopic Vaginal Ureter Diagnosed by Computed Tomography

A case of a single ectopic vaginal ureter in a 6-year-old girl with urinary incontinence is reported. Excretory urography and renal sonography failed to visualize the dysplastic kidney, but enhanced computed tomography clearly demonstrated a poorly functioning hypoplastic kidney, ectopic ureter and vagina filled with contrast medium.

Enuresis in an adult female with obstructive sleep apnea

Adult onset enuresis accompanied by obstructive sleep apnea has been reported rarely. A female patient was referred to our clinic with complaints of of a 15-year history of loud snoring and sleep apnea as well as enuresis, which was treated successfully with imipramine and acetazolamide. The mechanism of enuresis and its relationship to upper airway obstruction are reviewed here with reference to the findings of polysomnography and sleep cystometry.

Effects of opioid subtypes on detrusor overactivity in rats with cerebral infarction.

Aim:  In order to determine the influence of different opioid receptor subtypes on detrusor overactivity after left middle cerebral artery (MCA) occlusion, cystometric recordings were obtained in conscious rats.

Central Muscarinic Receptor Subtypes Regulating Voiding in Rats

PURPOSE Muscarinic receptors are distributed widely in the brain. A recent study revealed that central muscarinic receptors are involved in voiding regulation. However, to our knowledge the role of each muscarinic receptor subtype has not been resolved. Therefore, we evaluated the effect of intracerebroventricular administration of selective muscarinic M1 to M4 receptor antagonists on voiding function in rats. MATERIALS AND METHODS Female Sprague-Dawley rats were cannulated for intracerebroventricular infusion under halothane anesthesia. In experiment 1 cystometry was performed in conscious rats, and BC and maximal voiding pressure were measured. In experiment 2 a catheter was inserted via the bladder dome to the bladder neck and UPP was measured by saline infusion. Repeat cystostomy was performed, and saline infusion and discharge saline, BC, maximal IVP and minimal UPP were measured in conscious rats. Pirenzepine, methoctramine, pFHHSiD and MT-3 were used as selective M1, M2, M3 and M4 muscarinic receptor antagonists, respectively, which were injected intracerebroventricularly. RESULTS In experiment 1 pirenzepine and pFHHSiD increased BC and decreased maximal voiding pressure. Methoctramine and MT-3 decreased BC. In experiment 2 pirenzepine and pFHHSiD increased BC and minimal UPP, and decreased maximal IVP. Methoctramine and MT-3 decreased BC and maximal IVP. Minimal UPP remained unchanged. CONCLUSIONS Intracerebroventricular administration of muscarinic M1 and M3 receptor antagonists inhibited urination in conscious rats, while M2 and M4 receptor antagonists induced excitatory changes.