AUTOMATED NONINVASIVE MEASUREMENT OF CYCLOPHOSPHAMIDE-INDUCED CHANGES IN MURINE VOIDING FREQUENCY AND VOLUME

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Abstract
Purpose: We developed an automated noninvasive method for studying bladder function in mice. Changes in voided volume and frequency accompanying cyclophosphamide-induced cystitis were measured using computerized digital balances. Materials and Methods: Eight CRL CD-1 mice were given a solution of glucose and saccharin to increase urine output and studied during the dark cycle, when most voiding occurs. Urine fell directly onto electronic balance pans. The time and weight of each void was recorded. Computer programs adjusted for evaporative loss analyzed voiding data within and across sessions. After establishing stable voiding patterns 300 mg./kg. cyclophosphamide were administered intraperitoneally. The Wilcoxon signed rank test was done to compare median voided volumes, frequency and gm. per hour of urine produced before and after cyclophosphamide. Results: We implemented an automated method for voiding studies in mice. After cyclophosphamide administration the number of voids per hour increased and voided volume decreased. Some mice had as much as a 70% decrease in bladder volume and a tripling of urinary frequency. Mice responded by a sustained elevation in frequency and decreased voided volume as early as 24 hours after cyclophosphamide administration or by a pattern of delayed toxicity. Conclusions: This noninvasive technique measures changes in mouse voiding patterns with great sensitivity and minimal effort. The method is applicable to murine models of interstitial cystitis, detrusor instability and other abnormal voiding states. It may be used for evaluating potential therapies for such conditions.