Masaharu Ohmura

Effects of partial outflow obstruction on bladder contractility and blood flow to the detrusor: comparison between mild and severe obstruction.

Detrusor dysfunction secondary to partial outflow obstruction is caused in part by decreased blood flow to the detrusor. We investigated changes in blood flow to the bladder and in bladder function after inducing partial outflow obstruction. The urethras of male Sprague-Dawley rats were constricted by sutures to degrees representing either mild and severe obstruction. Blood flow to the bladder was measured by a Doppler flowmeter prior to and 7 days after obstruction. In vivo and in vitro experiments were performed 7 days after surgery. After cystometry was used to determine bladder capacity, the pressure at which micturition was induced, and maximum voiding pressure, the bladder was removed and placed in an organ bath where increases in intravesical pressure in response to field stimulation were evaluated. Finally, volume-pressure studies were performed in order to determine passive detrusor compliance and response to field stimulation at each specific capacity in vitro. Although blood flow to the bladder was significantly decreased by severe obstruction, no differences in blood flow between control and mildly obstructed bladders was observed. While maximum voiding pressure decreased in severely obstructed bladders, both the pressure at which micturition was induced and bladder capacity were increased. The response to field stimulation was increased by mild obstruction but decreased by severe obstruction, although bladder compliance was increased by both. The peak response to filled stimulation was observed at a larger capacity in severely obstructed bladders than the others. In conclusion, when outflow obstruction was mild, blood flow to the bladder remained unchanged and detrusor contractility increased. On the other hand, severe obstruction decreased bladder blood flow and induced deterioration of detrusor function.

Effects of long‐term partial outflow obstruction on bladder function in the rat

The effects of chronic partial outflow obstruction in rats were investigated. The urethra of male rats was partially obstructed for 3 or 6 months and bladder function was compared with that of age‐matched controls. Bladder function was studied in vivo by infusion cystometry and in vitro by measuring the response of bladder muscle strips to stimulation. Cystometrograms of outflow‐obstructed bladders were categorized into three types: type 1 was equivalent to a normal bladder; type 2 was characterized by large capacity, enhanced voiding pressure, and some residual urine; type 3 had the largest capacity, an impaired voiding pressure, and considerable residual volume (overflow‐type of incontinence). The type 3 bladder was the most frequently observed type in rats obstructed for 6 months.

Effect of Ageing on Blood Flow to the Bladder and Bladder Function

Ischemia, induced by atherosclerosis, is a common cause of disorders in the elderly. Bladder dysfunction in older people may be caused by detrusor ischemia. We compared blood flow to the bladder and detrusor function in vivo and in vitro in young (6-month-old) and aged (24-month-old) male Sprague-Dawley rats. In both young and old rats, blood flow to the bladder measured by a laser Doppler flowmeter decreased as intravesical volume increased and was smaller in old rats than in young rats. Cystometrograms performed under anesthesia showed that old rats had smaller voiding pressure and larger bladder capacity than young rats. In isolated bladders, the pressure increase in response to bethanechol and low frequency field stimulation were impaired by aging. Volume-pressure studies showed that in isolated bladders of old rats compliance was greater and peak response to field stimulation was observed at a larger capacity. These findings indicate that bladders of older rats have a larger capacity with good compliance, but less contractility. Aging changes correlate with a decrease in blood flow to the bladder.

Effects of ligation of the internal iliac artery on blood flow to the bladder and detrusor function in rat

Ischaemia induced by atherosclerosis is a common cause of disorders in the elderly, including impairment of bladder function. To evaluate experimentally the effects of ischaemia on detrusor function, we performed infusion cystometry and evaluated the morphologic findings in the bladder of the rat.Blood flow to the bladder of the rat was evaluated with a Doppler flowmeter before and after the unilateral or bilateral ligation of the internal iliac arteries. Reevaluation was done at one and two weeks after surgery. Bladder function was studied by infusion cystometry performedin vivo under urethane anaesthesia. Finally, histological examination was performed.Blood flow at mid-dorsal wall of the control bladder was inversely related to intravesical volume. Unilateral or bilateral ligation of the internal iliac arteries decreased blood flow to the bladder, which showed a complete recovery two weeks postoperatively. Infusion cystometry of the ischaemic bladder with bilateral ligation of the internal iliac arteries demonstrated a decrease in voiding pressure, an increase in bladder capacity, and an increase in pressure at which micturition was initiated vs. the control. The bladder with unilateral ligation of the artery showed a decrease in voiding pressure, with no change in the other parameters. Histological examination indicated that the bilateral ischaemia and ischaemic side of unilateral ischaemia led to a degeneration of the mucosa, and severe oedema in submucosal and muscle layers one week postoperatively. Degeneration of smooth muscle was predominant at 2 weeks. Contralateral side of the unilaterally ischaemic bladder showed oedema and congestion of the submucosa and smooth muscle.Ligation of the internal iliac artery decreased blood flow to the bladder significantly, which resulted in smooth muscle degeneration. Consequently,in vivo voiding pressure was impaired in the ischaemic bladder.

Effect of ischemia and partial outflow obstruction on rat bladder function

We investigated the effects of ischemia induced by ligation of the bilateral internal iliac arteries following partial outlet obstruction on changes in detrusor function in rat. Rats were divided into three groups: sham-operated control rats, rats with partial outlet obstruction, and rats with obstruction + ischemia. Bladder function was studied by the in vitro organ bath technique 7 days after surgery. The weight of the bladder was significantly increased in both the obstruction and obstruction + ischemia groups. The obstruction + ischemia group exhibited a greater increase in weight. The passive length-tension relationship of detrusor muscle strips showed that tissue elasticity was decreased and the active length-tension relationship demonstrated that the peak response was observed at a shorter tissue length in the obstruction + ischemia group compared with the other two groups. There was no difference in the passive and active length-tension relationships between the control group and the obstruction group. The contractile response to various kinds of stimulation (field stimulation, bethanechol, ATP, and KCl) increased in the obstruction group and decreased in the obstruction + ischemia group. These findings suggest that partial outflow obstruction alone increased bladder contractility in response to stimuli. However, ischemia reduced the contractility and elasticity of the bladder wall.

FUNCTIONAL RESTORATION OF RAT BLADDER AFTER SUBTOTAL CYSTECTOMY : IN VIVO CYSTOMETRY AND IN VITRO STUDY OF WHOLE BLADDER

Functional restoration of the rat urinary bladder following subtotal cystectomy was studied via in vivo infusion cystometry and an in vitro whole bladder model. After the bladder had been separated from the prostate, subtotal cystectomy was achieved by ligating the bladder completely at a level just above the insertion of the ureters into the bladder. Bladder function was investigated immediately and 7, 14, and 28 days after surgery. Bladder weight was reduced to 17% that in sham-operated controls immediately after surgery, but recovered to 76% of that in controls 28 days after the operation. In vivo capacity also increased after surgery from 13% that of controls to 59% 28 days later. However, voiding pressure remained low (34% of control) 28 days later. An in vitro whole bladder study showed that the response to field stimulation decreased significantly on day 7, but had recovered considerably by day 28. The maximal response to bethanechol decreased significantly 7 days after surgery, but recovered thereafter. The response to phenylephrine increased significantly immediately after surgery, but gradually returnd to the control level. An in vitro volume-pressure study showed that passive complance of the cystectomized bladder decreased after surgery, but improved with time. The peak of the active pressure increase to field stimulation occurred at a low infusion volume immediately after surgery, but bladder capacity increased gradually until 28 days later, when the maximal active pressure was obtained. Our results suggest that restoration of the bladder following subtotal cystectomy may not derive simply from an expansion of the bladder wall. Functional alteration involving the bladder base was also observed.

Elevated concentrations of the small stress protein HSP27 in rat renal tumors

The expression of two small stress proteins, αB crystallin and the 27-kDa heat shock protein (HSP27), was studied quantitatively and immunohistochemically in normal kidney and renal tumors in rats. Levels of αB crystallin in renal cell tumors tended to be higher than in normal kidney (P = 0.07), but with a wide range of values, whereas they were significantly lower in mesenchymal tumors (P < 0.0001). In contrast, HSP27 concentrations in both renal cell (mean ± SD: 1790 ± 940 ng/mg protein,n = 15) and mesenchymal (1260 ± 1080 ng/mg protein,n = 10) tumors were significantly higher than the normal kidney value (142 ± 30 ng/mg protein,n = 10,P < 0.0001). A positive correlation was found between αB crystallin and HSP27 levels limited to the renal cell tumor case (Pearsons correlation coefficient,r = 0.68,P < 0.01). Immunohistochemistry revealed the loops of Henle to be positive for αB crystallin, whereas HSP27 staining was positive in glomerular and interstitial vascular walls and epithelial cells of proximal and distal tubules. Positive immunostaining for αB crystallin was demonstrated in six of nine renal cell tumors (67%) studied and for HSP27 in all of the nine cases (100%).

Effects of Ethanol on Responses of Isolated Rabbit Urinary Bladder and Urethra

Background Acute ethanol ingestion increases the risk of urinary retention in patients with benign prostatic hyperplasia (BPH). To elucidate the mechanism of this effect, we investigated the in vitro effects of ethanol on lower urinary tract function in rabbits.

Response of Isolated Human Neurogenic Bladders to Tachykinins

Tachykinins act as stimulants of the isolated urinary bladder. However, the efferent role of tachykinins on detrusor function is controversial. We investigated the contractility of isolated human neurogenic bladders taken from patients with myelomeningocele or sacral agenesis, and tested the response to neurokinin A (NKA), neuromedin K (NKB), and substance P (SP). The contractile strengths were compared with normal controls. All tachykinins investigated induced significant contractions in both neurogenic and control bladders. The rank order of contractile potency was the same in both groups, namely, NKA > NKB > SP. The contraction induced by SP was not affected by atropine, but was completely blocked by [Sar9,Met(O2)11]-SP (a SP antagonist). Responses to electrical field stimulation were not changed by the SP antagonist. The contractile magnitude to field stimulation was also not altered by administration of 10(-6) M tachykinins. Responses of the neurogenic bladder to NKA and SP were significantly greater than the control. There were no differences in the response to KCl administration between the 2 groups. We conclude that hypersensitivity to NKA and SP in neurogenic bladders may contribute to bladder dysfunction in patients with sacral cord lesions.

Restoration of rat bladder function following release of short- and long-term partial outflow obstruction

Detrusor dysfunction does not recover in some patients with benign prostatic hyperplasia (BPH) even after prostate resection. ‘We studied the functional restoration of the rat bladder after release of short- or long-term outflow obstruction. Bladder function was assessed by in vivo infusion cystometry and an in vitro organ bath technique. There were no significant differences in bladder weight and contractile strength induced by stimuli in detrusor muscle strips from obstructed rats and age-matched control rats. After short-term obstruction the whole bladder pressure generated in vitro by field stimulation, bethanechol, ATP, and KCl completely recovered to control levels. In contrast, after long-term obstruction, the whole bladder pressure in response to field stimulation remained significantly lower than in controls. Infusion cystometry variables, including the pressure at which micturition was induced, maximal voiding pressure, capacity, and residual urine volume, were similar between controls and rats subjected to short-term obstruction. However, the maximal voiding pressure after long-term obstruction was significantly less than that of controls.