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

An experimental ischemic model of mouse urinary bladder was developed to st udy urothelium permeability and changes in cell ultrastructure. The bladder permeability barrier response to experimental ischemia (30-120 min) was in vestigated by means of indigo carmine dye, trypan blue and lanthanum nitrat e tracer, which were used as quantitative and qualitative indicators of uro thelial integrity. Changes to the urothelium were studied by light microsco py, and by scanning and transmission electron microscopy. It was establishe d 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 des quamation of viable urothelial cells. Urothelial damage occurs as funnel-sh aped wounds, which can extend into the lamina propria. They are proportiona l to the duration of ischemia and to the extent of reperfusion induced. Des quamated cells in the bladder lumen, when exposed to hypertonic and toxic u rine, gradually become irreversibly changed.