Micturition Studies

Male Wistar rats weighing 340-360 g are anesthetized. The left jugular vein is cannulated for drug injec- 

Intraluminal pressure signals are delivered to an amplifier and displayed on a four channel polygraph. Warm saline-soaked cotton wool swabs are laid around the exteriorized organ to maintain its temperature and to keep it moist in experiments involving the topical application of substances on the bladder dome. 

After a 15-min equilibration period at zero volume, variations in intraluminal pressure are recorded in response to continuous infusion of saline at a rate of 2.8 ml/h at 37 °C for 30-40 min by means of a peristaltic pump connected to the polyethylene tubing inserted into the bladder. This infusion rate simulates the maximal hourly diuresis within the physiological range. In each preparation the infusion is continued until micturition occurs. Micturition is referred as the emission of several drops of fluid during a sustained phasic contraction of the detrusor muscle which is followed by return to zero or, in any case, to a value lower than that recorded just before micturition. 

For both intravenous and topical administration, substances are dissolved in saline. 

The effect of substances on the compliance of the bladder wall is evaluated by comparing the volume-pressure-relationship of treated animals with that of controls. 

---

Moreau PM, Lees GE, Gross DR (1983) Simultaneous cystometry and uroflowmetry (micturition study) for evaluation of the caudal part of the urinary tract in dogs Reference values for healthy animals sedated with xylazine. Am J Vet Res 44 1774-1781... 

A good micturition study requires sequential filming (two spots/second) or a videotape recording (Potter et al. 1986) in order to detect voiding dysfunction (absence of coordination between blad-... 

Six placebo-controlled studies showed that duloxetine reduces incontinent episode frequency and the number of daily micturitions, increases micturition interval, and improves quality-of-life scores. These benefits were statistically significant but clinically modest. 

Controlled studies demonstrate that tolterodine is more effective than placebo and as effective as oxybutynin IR in decreasing the number of daily micturitions and increasing the volume voided per micturition. However, most studies have not shown a decrease in the number of daily UI episodes as compared with placebo. 

Kok AL, Burger CW, van de Weijer PH, Voetberg GA, Peters-Muller ER, Kenemans P. Micturition complaints in postmenopausal women treated with continuously combined hormone replacement therapy a prospective study. Maturitas 1999 31(2) 143-9. 

Other recent studies have reported that the 5-HT7 receptor is involved in mediating the effects of 5-HT on ileum peristalsis (107). the micturition reflex (108), and relaxation of the oviduct (109). 

Yaksh et al. (1986) described a chronic model for study of micturition in unanesthetized rats. A bladder catheter was implanted chronically through laparatomy and externalized percutaneously. 

Horvath et al. (1994) reported an ultrasonic method to study the influence of drags on micturition in intact rats. 

Conte et al. (1988) developed a cystometric technique for quantitative studies on physiopharmacology of micturition in conscious, freely moving rats. 

Maggi CA, Giuliani S, Santicioli P et al. (1987) Further studies on the mechanisms of the tachykinin-induced activation of the micturition reflex in rats evidence for the involvement of the capsaicin-sensitive bladder mechanoreceptors. Eur J Pharmacol 136 189-205... 

Tiflig B, Constantinou CE (1996) Videomicroscopic imaging of ureteral peristaltic function in rats during cystometry. J Pharmacol Toxicol Meth 35 191-202 Yaksh TL, Durant PAC, Brent CR (1986) Micturition in rats a chronic model for study of bladder function and effect of anesthetics. Am J Physiol 251 (Regulative Integrative Comp Physiol 20) R1177-R1185... 

As regards adverse effects, noxiptiline seemed to cause more mental symptoms, such as delirium (3). In one study in 44 patients, 9 developed delirium, there were mild manic symptoms in 6, dry mouth in 21, disturbed micturition in 2, and difficulty in accommodation in 3 (2), the last 3 being evidence of anticholinergic effects. 

Controlled studies have demonstrated that oxybutynin XL is significantly more effective than placebo and equally effective as oxybutynin IR in terms of reducing the mean number of UI episodes, restoring continence, decreasing the number of micturitions per day, and increasing urine volume voided per micturition (see Table 83-5).30.31A5-47.57-59... 

In the OPERA trial, oxybutynin XL was comparable to tolterodine long-acting (LA) in decreasing the mean number of incontinence episodes, but was superior in reducing weekly micturition frequency and achieving total dryness. In another study that pooled results of two open-label studies, tolterodine LA was associated with significantly greater patient-perceived improvement in bladder control and fewer withdrawals due to adverse effects than oxybutynin XL. 

Several studies have evaluated whether the clinical and urodynamic effects of a combination of estrogen and an a-adrenergic receptor agonist exceed those of the individual therapies in SUI. In general, combination therapy has resulted in somewhat superior clinical and urodynamic responses compared with monotherapy, including severity of complaints, amount of urine lost per episode, number of daily voluntary micturitions, number of leakage episodes per day, patient preference, pad use, maximum urethral closure pressure, functional urethral length, and pressure transmission ratio. 

Studies in humans confirm the in vitro tests while clinical trials show clear benefits in terms of increased micturition volume, decreased frequency, decreased nocturia and a decrease in prostate volume. 

Memantine. 3,S-Dimethyltricyclo[3.3.I.I3 ]decan-1-amine 3,S-dimethyl-l-adamantanamine 1 -amino-3,5-dimethyladamantane DMAA D 145. C.jH N mol wt 179.31. C 80.38%, H 11.81%, N 7.81%. Deriv of adaman-tine, q.v.. with anti-parkinson activity. Prepn of the hydrochloride K. Gerzon et al. J. Med. Chem. 6, 760 (1963) of the free base and hydrochloride J. Mills, E. Krumkalns, UJS. pat. 3,391,142 (1968 to Lilly). GC and mass spec studies of memantine metabolites W. Wesemann et al, Arznei-mittel-Forsch. 27, 1471 (1977), Effects in parkinsonian patients P. -A. Fischer er at., Ibid, 1487. Series of articles on distribution, effects on neurobiological processes, clinical studies in control of micturition and limb muscle mobility ibid. 32, 1236-1276 (1982). Clinical studies as antispasmod-ic agent H. Rohde, Fortschr. Med. 100, 2023 (1982). Pharmacodynamics and pharmacokinetics W. Wesemann et al, Arzneimittel-Forsch. 33, 1122 (1983). 

An animal study compared the effect of aclidinium versus tiotropium, ipratropium, or placebo on the urinary and kidney function of rats, dogs and pigs [76 ]. It included four subjects per animal and showed a significant decrease in the urine excretion rate, renal blood flow, and increase in peak micturition pressure associated with tiotropium and ipratropium, but not with aclidinium or placebo. These suggest that aclidinium is not expected to be associated with urinary retention or worsening kidney fimction. 

A basic study of the urinary tract should start with an explanation to the parents, and to the child if he or she is old enough to understand. The bladder is studied first, especially in infants, since reflex micturition is frequent when the transducer is placed on the abdominal wall (avoid unheated jelly). Examination of the full bladder includes analysis of urine echogenicity and the bladder wall. It is extremely important to look for dilated ureters(s) behind the... 

In a second step the video-urodynamic study itself is performed. Fluoroscopic video-cystourethrography is performed intermittently during the filling and storage phases. Fluoroscopy of voiding demands that micturition be performed in the erect position in older children, and for this a simple funnel-shaped device to fit the female perineum is utilized. 

Fig. 6.7. a VCU in a 7-year-old boy with dysuria, showing extrinsic compression of the urethra due to abnormal sphincter contraction during micturition. This functional anomaly should not be mistaken for posterior urethral valves. Urody-namic studies favor dysfunctional voiding with bladder-sphincter dyscoordination during voiding. Biofeedback physiotherapy was carried out. Clinical outcome was favorable, b Follow-up VCU shows normalization of urethral anatomy during... 

Yeung et al. (1995) suggested that incomplete coordination between detrusor contraction and urinary sphincter relaxation could be normal. In a further study by Yeung et al. (1998) two separate patterns of micturition could be distinguished a normal pattern typified by a continuous urinary stream coordinating with a detrusor contraction and an immature pattern typified by an interrupted stream and apparently discoordinated micturition. This is in agreement with our own observations. 

---