Early cellular and ultrastructural response of the mouse urinary bladder urothelium to ischemia

An experimental ischemic model of mouse urinary bladder was developed to study urothelium permeability and changes in cell ultrastructure. The bladder permeability barrier response to experimental ischemia (30-120 min) was investigated by means of indigo carmine dye, trypan blue and lanthanum nitrate tracer, which were used as quantitative and qualitative indicators of urothelial integrity. Changes to the urothelium were studied by light microscopy, and by scanning and transmission electron microscopy. It was established that ischemia primarily induces breakdown of the blood-urine permeability barrier by disruption of the tight junctions. It causes focal interruption of the contacts between the cells, which is followed by detachment and desquamation of viable urothelial cells. Urothelial damage occurs as funnel-shaped wounds, which can extend into the lamina propria. They are proportional to the duration of ischemia and to the extent of reperfusion induced. Desquamated cells in the bladder lumen, when exposed to hypertonic and toxic urine, gradually become irreversibly changed.