Division of Urology, Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
Neurourol Urodyn. 2018 Nov;37(8):2425-2433. doi: 10.1002/nau.23710. Epub 2018 May 19.
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.
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.
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 pO remained stable after an initial decline.
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.
慢性缺血是导致膀胱活动低下(UAB)的病理生理学的公认因素。尽管已知充盈过程中会发生相对缺血(即低血流量),但对于导致 UAB 的病理生理机制知之甚少。因此,我们开发了一种离体功能性猪模型,以研究短暂性缺血的作用以及是否存在自动调节,这是一种在某些重要器官中维持组织氧合的机制,也存在于膀胱中。
使用来自屠宰猪的膀胱,我们制备了一个离体灌注模型,在该模型中,我们研究了膀胱灌注流速对充盈阶段灌注压和组织氧合的影响。膀胱以 20ml/min 的初始流速灌注,然后以逐步递减的方式夹闭,直至无流量,然后恢复到初始流速。
我们发现流速与灌注压之间存在线性关系,直到流速降低到 5ml/min 以下,此时血管阻力降低;然而,组织 pO2 在初始下降后保持稳定。
这些发现表明,膀胱中可能存在一种内在的自动调节机制,使它在正常功能期间经历周期性的相对缺血。克服这种机制的因素,如完全或慢性缺血,可能在向逼尿肌活动低下的进展中至关重要,从而强调了在疾病早期阶段进行干预的重要性。