Increased Afferent Nerve Firing Is Correlated With the Detection of Bladder Wall Micromotion in a Perfused Ex-Vivo Porcine Model.

Introduction And Objective: Observable autonomous rhythmic changes in intravesical pressure, termed bladder wall micromotion, is a phenomenon that has been linked to urinary urgency, the key symptom in overactive bladder (OAB). However, the mechanism through which micromotion drives urinary urgency is poorly understood. In addition, micromotion is inherently difficult to study in human urodynamics due to challenges distinguishing it from normal cyclic physiologic processes such as pulse rate, breathing, rectal contractions, and ureteral jetting. Therefore, the goal of this study was to create a reproducible model of micromotion using an ex-vivo perfused porcine bladder, as well as to describe the relationship between micromotion and afferent nerve signaling.

Methods: Porcine bladders were reanimated using ex-vivo perfusion with a physiologic buffer. The pelvic nerve adjacent to the bladder was dissected, grasped with micro-hook electrodes and electroneurogram (ENG) signals were recorded at 20 kHz. Bladders were catheterized and intravesical pressure measurements were taken using a Laborie XT Urodynamics system. Bladders were filled to a fixed volume of 300 mL and control measurements were recorded. The bladders were then washed with 0.001 M carbachol (CCh) solution and refilled to 300 mL to induce micromotion, which was detected as rhythmic changes in intravesical pressure. ENG amplitude was calculated in μV, and nerve firing rate was calculated as number of spikes above baseline threshold per minute.

Results: Micromotion was induced by carbachol in 12/25 (48.4%) of trials as rhythmic changes in intravesical pressure after the instillation of carbachol but not in any control period. A fast Fourier transform (FFT) algorithm showed average peak dominant frequency component amplitude was significantly higher during the carbachol period when compared to the control period (0.47 vs. 0.01 cm-HO, p < 0.0001). Peak waveform frequency (1.13 vs. 1.54 cycles/min, p > 0.05) did not differ between control and carbachol periods. With regard to afferent nerve signaling, normalized average amplitude (0.66 ± 0.24 vs. 0.05 ± 0.08 μV) and firing rate (0.68 ± 0.28 vs. 0.18 ± 0.22 spike/min) for all bladders was significantly greater in the carbachol period when compared to the control period (p < 0.001).

Conclusions: Micromotion can be induced using instillation of carbachol in a perfused ex-vivo porcine bladder. Increased afferent nerve firing is observed during periods of micromotion. Thus, micromotion may drive afferent nerve signaling and may potentially contribute to urinary urgency, detrusor overactivity, and OAB. The development of an experimental ex-vivo porcine model for micromotion provides a reproducible method to study bladder micromotion and its potential role in the pathophysiology of urinary urgency and voiding dysfunction.