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MP94-05: Chronic Rat Model for Testing New Therapies for Stress Urinary Incontinence

Tuesday, May 16
7:00 AM - 9:00 AM
Location: BCEC: Room 253AB

Presentation Authors: Chrissie T. Wøien*, Thomas M. Andersen, Odense, Denmark, Travis K. Mann-Gow, Burlington, VT, Peter Zvara, Odense, Denmark

Introduction: Urethral sphincter function in a rat is assessed by measuring the leak point pressure (LPP). The current model uses urethane anesthesia and spinal cord injury, making the experiments terminal procedures. This study describes a new method, which allows repeated testing on the same animal.


Methods: Through a small skin incision, a modified 22G needle opened on one side to form a groove, was used to access the spinal canal between the L6 and S1 vertebrae. A 32G catheter was then inserted into the intrathecal (IT) space and the tip advanced to the level of T12. After minimum of 2 days, the rat was placed vertical on a tilt table and three micturition cycles were recorded under light isoflurane anesthesia (1.2 - 2%). Subsequently, an IT injection of lidocaine was used to suppress the micturition reflex. The pressure at which overflow incontinence started was recorded followed by manually evacuating the bladder and filling it to 50% of its capacity. Then the LPP was assessed using the Crede maneuver (CM).


Results: IT catheter insertion success rate was ~90%. Position of the IT catheter was confirmed by injection of lidocaine causing transient paraplegia in awake rat. Cystometry under light isoflurane anesthesia produced full micturition cycles with mean maximal pressure of 30.9 cm/H2O, (min. 18.6, max. 37.4) and mean intermicturition oscillatory pressure of 8.0 cm/H2O (min. 4.6, max. 11.9). IT administration of lidocaine completely blocked micturition contractions. The intravesical pressure at which overflow incontinence ensued was 29.6 cm/H2O (min. 24.0, max. 34.6). LPP using the CM was 31.0 cm/H2O (min. 18.5, max. 36.3).


Conclusions: In low concentration, isoflurane anesthesia preserves continence, bladder contraction and coordinated function between the bladder and sphincter. This makes it appropriate for testing LPP. Isoflurane anesthesia allows placing the animal vertical on the tilt table, and IT injection of lidocaine blocks micturition. The learning curve for IT catheter placement is steep. In most cases, the intravesical pressure at which overflow incontinence coincided closely with the LPP measured using the CM. This experimental design allows repeated evaluation of LPP in a single animal.

Source Of Funding: The Danish Council for Independent Research and Odense University Hospital

Chrissie T. Wøien

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