The aim of this project was to develop an ex-vivo porcine bladder model to test the effects of increasing durations of acute ischemia on detrusor function and to determine at what point those effects are reversible.

Porcine bladders were obtained from local abattoirs immediately after slaughter and perfused with oxygenated Krebs solution through cannulas placed in bilateral superior vesical arteries. Bladders were placed in a customized chamber to replicate physiologic conditions. Oxygenated perfusate was supplied at standard physiologic flow (4ml/min). Bladders were filled in a retrograde manner to 250 mL through a urethral catheter and intravesical pressures were continuously recorded throughout the experiment. At 250 mL, contractions were induced via intravesical infusion of a potassium enriched solution, and the bladders were emptied by releasing the urethral catheter at the peak of contraction. Total, passive, and active pressures were recorded for each contraction and data was normalized to the control fill. After equilibration, ischemia was induced by altering the rate of deliverance of the oxygenated perfusate. The following perfusion protocol was used for each fill, void cycle: control (4ml/min), partial ischemia (2ml/min), global ischemia (0ml/min) and reperfusion (4ml/min). Isovolumetric perfusion periods were held for 15 minutes or 30 minutes and results compared.

Nineteen porcine bladders were utilized, including 8 bladders in the 15 minute group and 11 bladders in the 30 minute group. With 15 minutes of ischemia, passive pressure increased 39% (p=0.03) with a reciprocal decrease in the active pressure of 23% (p=0.002) during global ischemia. However, total pressure remained constant. Values of passive and active pressure returned to baseline with reperfusion. (Figure 1a). With 30 minutes of ischemia, passive pressure remained unchanged during global ischemia. However, there was a decrease in total pressure 34% (p<0.001) and active pressure 61% (p<0.001), with incomplete return to baseline with reperfusion. (Figure 1b). Examples of urodynamic tracings of these results can be seen in Figure 2 with 15 minutes ischemia in Figure 2a and 30 minutes ischemia in Figure 2b.

In a perfused porcine bladder model there are measurable changes in detrusor function with ischemia. With 15 minutes of ischemia there is an increase in passive pressure, reciprocal decrease in active pressure with a recovery to baseline with reperfusion; representing a compensated, stiffer phase. With 30 minutes of ischemia there is a decrease in active pressure, a decrease in total pressure, with an incomplete recovery with reperfusion; representing a decompensated, underactive phase.

This study shows the utility of using an ex-vivo porcine bladder model to investigate the effects of ischemia on detrusor function. These results also provide mechanistic insight into the physiologic changes of ischemia-mediated voiding dysfunction.