Bladder augmentation in the prevention of cyclophosphamide-induced haemorrhagic cystitis in the rat model

Objective To evaluate the effects of cyclophosphamide on the bowel mucosa of the rat and to determine whether urothelium can be protected from the effects of haemorrhagic cystitis which can occur after treatment with cyclophosphamide. Materials and methods Thirty Sprague-Dawley rats were divided into three groups, 10 undergoing a control (sham) operation, 10 an ileal bladder augmentation and 10 a colonic bladder augmentation. Each rat underwent the appropriate surgical procedure and after a recovery period of 2 weeks, was injected with cyclophosphamide. Urine specimens were collected 24 h after the injection and analysed for gross and microscopic haematuria. The rats were killed humanely 48 h after injection and the bladders examined for haemorrhage, oedema, attenuation, inflammation and erosion. Results None of the 20 augmented rats developed gross haematuria and only four developed microscopic haematuria, compared with the control rats where sis of 10 developed gross haematuria and nine developed microscopic haematuria. In addition, the control rats had moderate to severe haemorrhage, oedema and attenuation compared with only mild changes in the augmented rats. This protection was significant for both the bowel mucosa and urothelium. Conclusions It is possible that the administration of cyclophosphamide in patients with urinary diversion carries little risk of haemorrhagic cystitis. We propose that this protective mechanism is secondary to a substance secreted by the intestinal mucosa that may bind acrolein and render it inactive. Alternatively, this may be secondary to the production of mucus and its ability to coat and protect the epithelium.