Uzoma A Anele1, Paul H Ratz2, Andrew F Colhoun1, Sydney Roberts3, Ryan Musselman3, Randy A Vince1, John E Speich3, Adam P Klausner1. 1. Division of Urology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia. 2. Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia. 3. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia.
Abstract
AIMS: Chronic ischemia is a recognized factor in the pathophysiology of underactive bladder (UAB). Although relative ischemia (ie, low blood flow) is known to occur during filling, little is known regarding the pathophysiology that leads to UAB. Therefore, we developed an ex vivo functional porcine model to investigate the role of transient ischemia and whether autoregulation, a mechanism that maintains tissue oxygenation in certain vital organs, also exists in the bladder. METHODS: Using bladders from slaughtered pigs, we prepared an isolated perfused model where we studied the effects of bladder perfusion flow rate on perfusion pressure and tissue oxygenation during the filling phase. Bladders were perfused at an initial flow rate of 20 mL/min and then clamped in a sequentially decreasing stepwise manner down to no flow and back to the initial flow rate. RESULTS: We found a linear relationship between flow rate and perfusion pressure until the flow rate decreased below 5 mL/min at which point the vascular resistance decreased; however, tissue pO2 remained stable after an initial decline. CONCLUSIONS: These findings suggest that there may be an intrinsic autoregulatory mechanism in the bladder that allows it to undergo cyclic episodes of relative ischemia during its normal function. Factors that overcome this mechanism such as complete or chronic ischemia may be critical in the progression to detrusor underactivity and thereby highlight the importance of intervention during the early phases of this disease process.
AIMS: Chronic ischemia is a recognized factor in the pathophysiology of underactive bladder (UAB). Although relative ischemia (ie, low blood flow) is known to occur during filling, little is known regarding the pathophysiology that leads to UAB. Therefore, we developed an ex vivo functional porcine model to investigate the role of transient ischemia and whether autoregulation, a mechanism that maintains tissue oxygenation in certain vital organs, also exists in the bladder. METHODS: Using bladders from slaughtered pigs, we prepared an isolated perfused model where we studied the effects of bladder perfusion flow rate on perfusion pressure and tissue oxygenation during the filling phase. Bladders were perfused at an initial flow rate of 20 mL/min and then clamped in a sequentially decreasing stepwise manner down to no flow and back to the initial flow rate. RESULTS: We found a linear relationship between flow rate and perfusion pressure until the flow rate decreased below 5 mL/min at which point the vascular resistance decreased; however, tissue pO2 remained stable after an initial decline. CONCLUSIONS: These findings suggest that there may be an intrinsic autoregulatory mechanism in the bladder that allows it to undergo cyclic episodes of relative ischemia during its normal function. Factors that overcome this mechanism such as complete or chronic ischemia may be critical in the progression to detrusor underactivity and thereby highlight the importance of intervention during the early phases of this disease process.
Authors: Andrea Balthazar; Zachary E Cullingsworth; Naveen Nandanan; Uzoma Anele; Natalie R Swavely; John E Speich; Adam P Klausner Journal: Neurourol Urodyn Date: 2019-04-04 Impact factor: 2.696
Authors: Dielle L M Duval; Samuel Weprin; Naveen Nandanan; Zachary E Cullingsworth; Natalie R Swavely; Andrea Balthazar; Martin J Mangino; John E Speich; Adam P Klausner Journal: Int Urol Nephrol Date: 2021-07-01 Impact factor: 2.266
Authors: Zachary E Cullingsworth; Naveen Nandanan; Natalie R Swavely; Konstantin Frolov; Randy Vince; Rebecca Zee; Theodore Cisu; Adam P Klausner; John E Speich Journal: Transl Androl Urol Date: 2021-06