Post-irradiation bladder dysfunction: development of a rat model.

Abstract

The aim of this research was to establish a small animal model for the functional and morphological study of post-irradiation bladder dysfunction. Young adult female Wistar rats were X-irradiated with single doses of 10, 15, 20 or 25 Gy. Filling cystometry was performed to assess changes in reservoir function: the volume infused to produce a rise in intravesical pressure of 5 cmH2O was calculated as an index of compliance. A biphasic reduction in this index was noted in animals receiving 15-25 Gy; the first reduction developed at about 4 weeks, and the second started at 3-4 months and persisted at 6 months. Bladder tissue was taken at this time (6 months post-irradiation) for morphological study. Histological examination demonstrated an increased mast cell density in the irradiated bladders, but was otherwise non-specific; fibrosis was discernible in only half of the 18 animals studied. Electron microscopy showed focal degeneration of smooth muscle cells, and in some areas there was selective degeneration of unmyelinated axon profiles. The biphasic reduction in the compliance index is consistent with the timing of the symptoms of the acute and late irradiation reactions reported by radiotherapy patients. Changes in axon profiles and mast cell density may be of functional significance.