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N46 Animal models of overactive bladder: Cyclophosphamide (CYP)-induced cystitis in rats

      Introduction and Objectives

      Cyclophosphamide (CYP) treatment induces chemical cystitis leading to bladder overactivity (OAB) in animals and humans. There is a great number of OAB models evaluations, which consider the bladder histology, as well as alterations in neurochemical, electrophysiological properties of bladder afferent neurons and reflex arcs activity in the spinal cord. However there are no data differentiating cystometrically acute and chronic models of OAB induced by CYP under urethane anaesthesia. The aim of this study was to investigate the influence of acute and chronic models of CYPinduced cystitis on urinary bladder motor activity in rats.

      Material and Methods

      Experiments were performed on 30 adult female Wistar rats. Acute and chronic chemical cystitis was induced by CYP. CYP was administrated intraperitonealy in a single dose 200 mg/kg i.p. to elicit acute inflammation or in 75 mg/kg i.p. every 3rd day for 7 days to elicit chronic inflammation. The animals were randomly divided into 3 groups of ten animals each: group I (healthy rats), group II (acute CYP treatment – single dose) and group III (chronic CYP treatment – 4 doses). Cystometry was performed 1 h after surgical procedure, under urethane anaesthesia, in all groups. The surgical procedure was performed after 5 h of CYP administration in group II and after 24 h of the 4thCYP dose administration in group III. Saline solution was infused at a rate of 0,046 ml/min. continuously into the bladder. The measurements in each animal represent the average of 5 bladder micturition cycles, after obtaining repetitive voiding. We recorded: BP (basal pressure), PT (threshold pressure), MVP (micturition voiding pressure), ICI (intercontraction interval), Compliance, fBC (functional bladder capacity). Moreover we calculated MI (motility index) in 10-minutes intervals. In addiction we analysed DI (detrusor index) in group I and DOI (detrusor overactivity index) in group II and III.

      Results

      After acute and chronic CYP administration we observed respectively significant decrease of MVP (21.5% in both groups), ICI (69.2% or 58.2%), fBC (69.4% or 58.3%). Also increase of BC (200% or 133%), DOI (580% or 200%), MI (76% or 38%). Compliance was significantly decreased (45.5%) only in chronic OAB. Significant changes between CMGs parameters in acute and chronic OAB were only concerned with detrusor overactivity characterized by DOI.

      Conclusions

      In summary, our present findings show that acute and chronic “chemical” CYP-induced cystitis lead to the overactivity of urinary bladder in rats. We have found no significant differences in basic CMGs parameters, such as BP, PT, MVP, ICI, fBC, Compliance in rats with acute or chronic OAB models. Our current results prove that both models are equally credible for cystometric evaluation.