The effect of intravesical sodium nitroprusside on idiopathic detrusor overactivity
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Sodium nitroprusside
Nephrology
Cystometry
THE study of bladder function by cystometry has led to the conclusion that the bladder acts as a single unit. This was inevitable, since the cystometer registers the summation of changes in intravesical pressure resulting from detrusor contraction, without disclosing how such changes are brought about. Observation of the bladder during micturition under the fluoroscope, however, makes it quite clear that this concept is not entirely correct.There are two functional units of the bladder that, by their synergism under normal circumstances, comprise the total detrusor function. These two units, which consist of the bladder base and of the dome, . . .
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Urination
Urinary bladder disease
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Various animal models have been used in research into bladder dysfunction, and in vivo cystometry is a common method to analyze bladder function in animals. However, it is rather difficult to perform reliably in small animals. Transabdominal bladder ultrasonography combined with cystometry in urethane-anesthetized mice have revealed physical inhibition of bladder wall movement by a bladder catheter conventionally placed in the bladder apex. For reliable evaluation of mouse lower urinary tract function, we established a novel cystometry method in which a catheter was placed in the bladder anterior wall, in combination with bladder ultrasonography. This new method allowed the bladder to be well distended (i.e., larger maximum bladder capacity, lower pressure threshold, higher voided volume, and higher bladder compliance compared with conventional methods), which reflected more spontaneous voiding than conventional cystometry methods. We also demonstrated the usefulness of bladder ultrasonography for analysis of mouse bladder function, especially bladder dynamics, maximum bladder capacity, and post-voiding residual volume. We analyzed bladder functional changes in lipopolysaccharide (LPS)-induced cystitis by combining bladder ultrasonography and this new cystometry method. Bladder ultrasonography revealed a rapid decrease in bladder capacity, and cystometry showed a rapid decrease in voided volume due to intravesical LPS instillation. This new cystometry method also revealed a rapid decrease in bladder compliance caused by LPS instillation, which was not detectable by conventional methods. The combination of ultrasonography and the new cystometry method may become a powerful tool for analysis of mouse bladder function and could contribute to the development of new treatments for bladder dysfunction.
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To evaluate the role of bladder afferent fibers in the hypogastric nerves (HGN) in modulation of the micturition reflex induced by chemical bladder irritation, voiding behavior, continuous cystometry, and spinal c-fos expression following intravesical acetic acid instillation were investigated in rats with or without HGN transection. Voiding behavior and continuous cystometry were examined in unanesthetized conscious rats. Following chemical bladder irritation, a significant increase in urinary frequency associated with a marked decrease in the voided volume per micturition, was noted in control rats with the intact HGN, but not in HGN-transected rats. Continuous infusion of acetic acid in control rats elicited irritative bladder responses characterized by a marked decrease in the intercontraction interval and a marked increase in maximal vesical pressure, both of which were absent in capsaicin-desensitized rats. HGN transection prevented the decrease in the intercontraction interval but not an increase in maximal vesical pressure following chemical bladder irritation. Compared with saline infusion, acetic acid infusion caused a significant increase in c-fos expression at L(1) and L(6) of the spinal cord, and HGN transection significantly reduced c-fos expression in the dorsal horn of the spinal cord at L(1) but not at L(6). These results suggest that capsaicin-sensitive bladder afferent fibers in the HGN, which travel through the rostral lumbar spinal cord, have a role in urinary frequency caused by chemical bladder irritation.
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Isotonic and isometric cystometry was used in anesthetized cats, some of which had their spinal cord severed previously. Reflex contraction of the bladder was obtained by electrical stimulation of the central stump of the first three sacral dorsal roots. Only in one animal out of 14, bladder contraction followed stimulation of the distal stump of sacral roots when the ventral roots had been cut. Stimulation of the distal stump of ventral roots showed that the major efferents to the bladder from the sacral cord traveled through S3. Surprisingly, consistent but smaller bladder contractions developed when the distal stumps of the ventral roots of L5 and L6 were stimulated. It was impossible to establish whether these represented activation of the detrusor or other vesical muscle, and pharmacological tests failed to differentiate between the lumbar and sacral-driven contractions.
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In 63 cases of paediatric enuresis of both functional and organic type cystometry was carried out using a modern pressure recording technique. The patients have been divided into 3 groups from their history and clinical findings. The findings from the cystometrogram have been divided into 5 main groups. To determine whether cystometry can give further information these 2 groupings have been correlated with one another. The conclusion reached is that cystometry can give valuable information in all cases of X-ray suspected or verified bladder obstruction and in all cases of reduced bladder capacity with negative clinical findings.
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Interstitial cystitis (IC) is a disease of the urinary bladder that causes increased urgency to void and pelvic pain. It is commonly thought that increased bladder sensations in IC are due to sensitization of bladder afferent nerves by inflammatory mediators. Current therapies aimed at known targets in the inflammatory or nociceptive pathways have, to date, been ineffective at reducing the symptoms in IC patients. To find potential new treatments for IC, we expressed a non‐native chloride channel (EG3RF) in bladder afferent neurons. This family of channels can be activated by either inflammatory conditions or by an exogenous pharmaceutical compound, but has no activity under normal physiological conditions. We hypothesize that successful transfection of the EG3RF chloride channel into rat bladder afferent nerves will diminish bladder hyperexcitability in the cyclophosphamide model of bladder inflammation. To transfect bladder afferent nerves, an expression plasmid containing the sequence for EG3RF was encapsulated in liposomes and instilled into the urinary bladder of Sprague Dawley rats using a transurethral catheter. Bladder activity was measured 1–2 weeks later using metabolic cages or bladder cystometry. Bladder inflammation was induced by intraperitoneal injection of cyclophosphamide (CYP, 150 mg/kg) 1 hour prior to measurement of bladder activity. Successful expression of the EG3RF channel up to 2 weeks following transfections was confirmed in the bladder smooth muscle, urothelium and dorsal root ganglia (T11–12, L1–L2 and L6‐S1 levels) using RT‐PCR, Western blot, and immunofluorescence analyses. Metabolic cage and cystometry experiments indicated no differences in voiding function between the control and non‐inflamed EG3RF‐transfected animals. However, EG3RF‐transfected rats were resistant to the excitatory effects of cyclophosphamide treatment. Treatment with cysteamine, which has been shown to activate EG3RF, decreased CYP‐induced bladder activity in both metabolic cage and cystometry experiments (31 mg/kg ip or iv, respectively) in EG3RF‐transfected rats but was ineffective in control rats. Intravesical instillation of cysteamine (5 mM) during cystometry in EG3RF‐transfected rats excited bladder reflexes while iv administration (31 mg/kg) decreased peak micturition pressure. These data suggest that expression of a non‐native chloride channel in bladder afferent nerves may be an effective treatment for painful bladder disorders such as interstitial cystitis. Further development of the technique may lead to significant advances in efficacy over existing treatments. Support or Funding Information T32 GM075770 (Xu); K01 DK106115 (Beckel); R01 DK091253 (de Groat)
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To examine the effects of a different number of daily bladder squeezes on bladder dysfunction in mice with spinal cord injury (SCI).Spinal cord was transected at the Th8/9 in female C57BL/6N mice. Their bladders were manually squeezed to eliminate urine inside every day for 4 weeks. The mice were divided into three groups depending on the number of bladder squeezes; A: once daily, B: twice daily, C: three times daily. Four weeks after transection, single-filling cystometry were performed under an awake condition. NGF in the bladder mucosa and mRNA expression of P2X receptors and TRP channels in L6/S1 dorsal root ganglia (DRG) were measured.Bladder weight in group C was less than that of group A. Bladder capacity, post-void residual, and the number of non-voiding contractions during the storage phase were significantly larger in group A compared to group B or C. The level of NGF in groups C were lower compared to group A or B. The expression of P2X3 and TRPA1 in groups B and C was decreased compared to group A. The expression of P2X2 was decreased in groups B compared to group A.The post-injury bladder management after SCI with an increased number of daily bladder emptying improves the storage and voiding bladder dysfunction associated with the reduction of NGF in the bladder as well as P2X and TRP transcripts in lumbosacral DRG.
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✓ The authors report over 100 sacral root blocks performed in 50 patients with detrusor activation by air cystometry. The detrusor reflex was abolished with unilateral sacral blocks in over 50% of the patients. The nerve roots most frequently innervating the bladder were S-3 and S-4. Most of these patients suffered from multiple sclerosis and had spinal cord involvement. The possible pathophysiology and its significance regarding urinary bladder innervation is discussed.
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The aim of this study was to explore the possibility of using rabbit bladder as a model for experimental detrusor electrostimulation research. In a study of urinary bladder activity induced through electrostimulation of the ventral roots, the functional and morphological parameters of the rabbit detrusor were investigated. Under general anaesthesia, open electrostimulation of ventral spinal roots leading towards the detrusor (usually S2, S3) was performed in 20 rabbits. Detrusor response was recorded by repeated electromyography and cystometry in two groups: animals with naturally concentrated urine content (Group A, eight rabbits) and animals after flushing and filling the bladder with saline (Group B, 12 rabbits). Histological examination of bladder wall was performed in both groups. The measured values were compared to one another as well as with data from the veterinary and human literature. The histological specimens were compared with histological specimens of human bladder. The reaction of detrusor fibres was detectable by electromyography in all cases. Elevation of intravesical pressure as a consequence of detrusor contraction was more difficult to detect, as this depends more on the density of the intravesical content. The pressure rise in Group B had a higher amplitude - up to 15 cm H2O versus 5 cm H2O in the first group (P = 0.00046). Histological examination of bladder wall from the two groups of rabbits showed no differences. In comparison with the bladder wall in humans, the only differences found were significantly thinner detrusor layers relative to the overall thickness of bladder wall. It is possible to use rabbit bladder for research into experimentally electrostimulation-induced activity of the detrusor or for experimental detrusor reinnervation research. It is necessary, however, to take into account certain limits - the lower contractility of the bladder wall and the need for qualitative control of bladder content. The present results also suggest that the physiological micturition of rabbits is probably more dependent on abdominal pressure than in humans.
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Exogenous NGF or saline was delivered to the detrusor smooth muscle of female rats for a two-week period using osmotic mini-pumps. We then determined: (1) bladder function using conscious cystometry; (2) organization of micturition reflexes using Fos protein expression in lumbosacral (L5-S1) spinal cord neurons; (3) calcitonin gene-related peptide (CGRP)-immunoreactivity (IR) in lumbosacral spinal cord segments. An osmotic pump infused 0.9% NaCl (n = 6) or NGF (n = 6)(2.5 μg/μl solution; 0.5 μl/hr) for two weeks into the bladder wall. NGF bladder content was determined by enzyme-linked immunoassays. Bladder function was assessed with conscious cystometry. Immunohistochemical and imaging techniques were used to determine the distribution of Fos-IR cells and CGRP expression in the L5-S1 spinal cord in saline and NGF-treated rats two hours after intravesical saline distention. Fos expression and CGRP-IR in NGF-treated rats with bladder distention was compared to that observed in cyclophosphamide (CYP; 75 mg/kg; i.p.) treated rats with bladder distention. Two-week infusion of NGF into the bladder wall increased bladder weight, reduced bladder capacity (60%), reduced the intercontraction interval (60%) and increased the amplitude of non-voiding contractions. NGF treatment and intravesical saline distention (2 hr) increased expression of Fos protein in L6-S1 spinal cord and altered the distribution pattern of Fos-IR cells. CGRP-IR in the lumbosacral spinal cord was also increased after NGF treatment. These data suggest that NGF infusion into the bladder wall induces bladder overactivity, can reveal a "nociceptive" Fos expression pattern in the spinal cord in response to a non-noxious bladder stimulus and increases CGRP-IR in the lumbosacral spinal cord.
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