Urodynamic Studies and Telemetric Monitoring of Bladder Function After Traumatic Thoracic Spinal Cord Injury in Minipigs

Keung M1, Webster M2, Streijger F2, Fisk S2, Chen K2, Manouchehri N2, Tigchelaar S1, So K2, Stothers L3, Kavanagh A3, Kwon B4

Research Type

Pure and Applied Science / Translational

Abstract Category

Research Methods / Techniques

Abstract 116
ePoster 2
Scientific Open Discussion Session 8
On-Demand
Animal Study Basic Science Pre-Clinical testing
1. Department of Neuroscience, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada, 2. International Collaboration on Repair Discoveries, Vancouver, BC, Canada, 3. Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada, 4. Department of Orthopaedics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
Presenter
M

Martin Keung

Links

Abstract

Hypothesis / aims of study
We have previously established a large animal model of traumatic spinal cord injury (SCI) using the Yucatan minipig, and while many studies have been performed to evaluate hindlimb function and other physiological responses to SCI, we have not previously characterized the resultant lower urinary tract (LUT) dysfunction in these animals. There is currently a need for a large animal model of neurogenic bladder dysfunction for the development and testing of novel human-sized devices or treatments that aim to improve bladder function. The current gold standard for characterizing LUT dysfunction is urodynamics. Unfortunately, there are recognized limitations to urodynamics, including the fact that it only provides a snapshot of bladder function under a non-physiological, retrograde filling of the bladder which may induce unfavorable urodynamic parameters. An alternative approach to characterizing LUT function is with an implanted radio-telemetric system that can provide real-time measurements of detrusor pressure (Pdet) and external urethral sphincter (EUS) activity from within an animal in a physiological setting. In this study, we attempted to establish a method for using an implanted telemetry system to monitor Pdet and EUS activity in our pig model of SCI. With this, we sought to (1) monitor LUT function in a physiological setting and (2) generate telemetric urodynamic reference data.
Study design, materials and methods
A four-channel Stellar telemetry transmitter (TSE Systems, Chesterfield, MO, USA) was implanted into the side flank of female Yucatan minipigs (N=2). The solid-state pressure catheters were inserted into the dome of the bladder to measure the intravesical pressure (Pves) and into the abdominal cavity to measure the abdominal pressure (Pabd). Pdet was calculated by subtracting Pabd from Pves. Two biopotential electromyography (EMG) leads were inserted down and alongside the urethra to measure the activity of the EUS. Telemetric recordings in a physiological setting were performed weekly for 12 weeks pre-injury. Urodynamic studies with concurrent telemetric recordings were performed in the uninjured pigs to establish a baseline before SCI. A T10 contusion and compression SCI was induced 12 weeks after implantation by dropping a 50 g weight from a height of 20 cm on the exposed spinal cord. After a one-week recovery period, telemetric recordings in a physiological setting were performed weekly for 4 weeks. Urodynamic studies with concurrent telemetric recordings were performed at 3 weeks post-SCI. At the end of the study, the animals were euthanized, and their bladders were harvested for histological evaluation.
Results
Weekly recordings of LUT function in uninjured pigs demonstrated visible detrusor contractions at the time of the void with consistent changes in Pdet. Uninjured pigs also demonstrated appropriate relaxation and contraction of the EUS as measured with the EMG sensor, similar to healthy humans. Concurrent telemetric recordings during urodynamic studies revealed comparable pressure and EMG tracings during both the filling and voiding phase in both uninjured and SCI pigs. Comparison of the voiding time during urodynamic studies versus in a physiological setting revealed a voiding time approximately 3 times longer during urodynamic studies in one uninjured pig.
Interpretation of results
Comparable Pdet and EMG tracings between the urodynamics and telemetry systems were observed in both uninjured and SCI pigs. These findings suggest that telemetric monitoring of LUT function is feasible in the minipig, and may provide an alternative or adjunct to urodynamic studies for characterizing LUT dysfunction after SCI.
Concluding message
Urodynamic studies may potentially alter physiological bladder and EUS function making it difficult to translate findings from animal studies to human studies. This is especially important in the context of neurogenic bladder dysfunction where there is currently a lack of a large animal model for the development and testing of novel human-sized devices that aim to improve bladder function. These telemetry systems can be used to capture long-term physiological measurements of LUT function in awake animals to better characterize changes in LUT function after SCI and to assess the efficacy of treatments.
References
  1. Jae H. T. Lee, Claire F. Jones, Elena B. Okon, Lisa Anderson, Seth Tigchelaar, Paul Kooner, Tamara Godbey, Bev Chua, Gordon Gray, Rhonda Hildebrandt, Peter Cripton, Wolfram Tetzlaff, and Brian K. Kwon. (2013). Journal of Neurotrauma, 30:3, 142-159.
Disclosures
Funding Department of Defense Clinical Trial No Subjects Animal Species Pig Ethics Committee University of British Columbia Animal Care Committee
08/05/2024 18:51:28