Cyclosporine A impairs wound healing of ureterocystoneostomy in rats. Scanning electron microscopic examination.

The effect of cyclosporine A (CsA), an immunosuppressive agent used in transplantation, on wound healing following microsurgical neoimplantation of a ureter in the bladder of 63 SIV ZUR rats was examined morphologically using the light and scanning electron microscopes and functionally by radiography. Following ureterocystoneostomy (UCN) on the right side, the animals in Group I (control group) received 1.0 ml CsA solvent (0.1 g ethanol and 0.3 g intralipid) per day. Group II received 12.5 mg/kg/day CsA and Group III 17.5 mg/kg/day CsA. All drugs were administered i.p. A third of the animals in each group were reoperated 7, 14 or 28 days after UCN. At these time intervals, there were no radiologically demonstrable differences in the operated side. Examination under the scanning electron microscope indicated delayed restitution of epithelium in the bladder for rats which had received CsA as compared to the control group. In the area of the UCN, CsA caused dose-independent retardation of the regenerative hyperplasia associated with wound healing (Group I: max. 7 days after UCN: Group II and Group III, max. 14 days after UCN). Hyperplastic areas had ropy microridges and uniform short microvilli. Where the hyperplasia exhibited nodular and papillary formation, also histologically more evident under CsA, occasional epithelial cells had pleomorphic microvilli on their luminal surface. Unlike other known premalignant changes of this kind, the frequent occurrence of pleomorphic microvilli under CsA was reversible. In general, CsA led to dose-unrelated protraction of UCN wound healing with no lasting functional disturbance in rats.