Bladder telemetry: A new approach to evaluate micturition behavior under physiological and inflammatory conditions

Abstract

Aims: To establish a new approach to cystometry using telemetry in conscious rats and to use this technique to determine the role of conscious decision making processes with respect to the initiation of voiding in physiological, inflammatory, and painful conditions. Methods: The pressure transducer of a telemetric transmitter was implanted in the dome of the urinary bladder. After a recovery period of at least 1 month, several investigations of urodynamic parameters were performed after diuresis activation by a pulse of furosemide. The model was characterized by tolterodine and mirabegron under physiological conditions and same animals were reused to evaluate the modification of the voiding pattern under bladder inflammation induced by cyclophosphamide. Results: The quality of traces and measurement of parameters recorded telemetrically were comparable to those with conventional cystometry. Furosemide induced a reproducible transient increase of urine production and a series of voids that persisted for 60 min. Tolterodine reduced the amplitude of micturition contractions although mirabegron was devoid of any effect. Seven hours after injection of CYP, voiding frequency increased significantly and the micturition amplitude contraction was not altered. However, the mean volume voided during individual micturitions and the total voided volume decreased. During a second exposure to furosemide 24H after CYP injection, the micturition pattern returned to control, however, the micturition volume was still lower than in control. Conclusion: This telemetric model appears to be as accurate as previously described in conscious conventional cystometry, and allows the repeated evaluation of compounds which may modulate the voiding patterns. Neurourol.

F16357, a novel protease‐activated receptor 1 antagonist, improves urodynamic parameters in a rat model of interstitial cystitis

“…When the furosemide challenge was repeated at 24 h, the total voided volume was reduced by about 60% when compared with the 7 h time point, thus affecting the number of micturitions (only 4 ± 1). This reduction in total voided volume, despite a reduced voiding frequency, was in accordance with data previously obtained, and corresponded to a significant fall in the rate of urine production as previously reported (Monjotin et al , ). The intravesical administration of F16357 30 μM significantly reduced the micturition frequency and increased the individual voided volumes in a comparable magnitude as those at 7 h ( P < 0.05).…”

“…Interestingly, furosemide induced a different effect on urine production at the two different times of recording; 24 h after CYP injection, the number of voids was reduced markedly in all groups. We have previously reported the same results after water loading instead of the furosemide pulse (Monjotin et al , ), thus eliminating a possible interaction between furosemide and CYP or its metabolites, or a loss of the pharmacological efficacy of furosemide during the second pulse. These observations could probably be induced by a major effect of CYP on kidney function (Kim et al , ).…”

“…In the next part of this study, the effects of F16357 were examined in an integrative animal model of IC induced by CYP. As described previously (Monjotin et al , ), radiotelemetry enables continuous recording of urodynamic parameters in fully unrestrained conditions in conscious animals. The bladder is not filled artificially with saline but urine following as part of an endogenous diuresis.…”

“…Before cystometric analyses, all instrumented rats were acclimatized to the experimental environment and basal urodynamic parameters established for all telemetered rats using a furosemide challenge as described previously (Monjotin et al , ).…”

“…Importantly, this acute model demonstrates many features of IC in humans. We have recently described a telemetric approach to evaluate, in the same conscious animal, urodynamic parameters in control conditions and after CYP injection (Monjotin et al , ). We now use this approach to evaluate drugs acting on lower urinary tract dysfunctions induced by CYP.…”