Decreasing Arterial Flow in the Ex Vivo Functional Pig Bladder Model Demonstrates Preservation of Tissue Oxygenation and Non-linear Decrease in Perfusion Pressure: Potential Mechanisms for Underactive Bladder and Vascular Autoregulation
Detrusor dysfunction, specifically underactivity, is an increasingly recognized phenomenon; however, contributing underlying mechanisms are poorly understood partly due to the lack of appropriate functional models for adequate study. The role of vascular resistance in maintaining tissue oxygenation (TpO2) upon reductions in tissue perfusion in bladder has never previously been evaluated. Therefore, we developed a model to evaluate the dependencies of vascular perfusion pressure and TpO2 on perfusion flow in isolated pig bladder.
Bladders from local abattoirs were harvested and prepared. Vesical arteries were cannulated and perfused. Intravesical pressure was measured via a cannulated ureter. After 1hr equilibration at perfusion flow of 20ml/min, the bladder was filled to 500mL via urethral catheter and re-equilibrated for 30min. Vascular resistance was assessed over a range of vascular flows by a stepwise decrease in flow rate by 5ml/min increments to 0ml/min and observed for 15-30min following each perturbation. Intravesical pressure, perfusion pressure, and TpO2 were recorded.
Bladders from 11 pigs were studied. Perfusion pressure initially decreased linearly with decreasing flow rate; however, demonstrated an inflection at lower flow rates (Fig1a, p<0.05). However, TpO2 remained stable at lower flow rates (Fig1b, p=0.24). The average bladder pressure trended downward with decreasing flow rate (Fig1c p>0.05). Perfusion pressure increased and decreased with intravascular phenylephrine or nitroglycerin. (Fig1d).
Maintenance of bladder TpO2 despite decreasing flow indicates involvement of an active, compensatory mechanism. The notable inflection from the expected perfusion pressure curve at lower flow rates may demonstrate this mechanism and may represent autoregulation. Although responsivity to vasoactive agents suggests capacity for vascular tone regulation, vascular resistance was constant over flow ranges of 20-0ml/min. Resting bladder tone may also be influenced by vascular flow rate. Further study is necessary to define these regulatory mechanisms which may help identify novel pathways involved in understanding or treating underactive bladder.