Moderated Poster

Poster, Podium & Video Sessions

MP26-02: Differential responsiveness to neurostimulation across the bladder filling cycle in rodents

Saturday, May 13
7:00 AM - 9:00 AM
Location: BCEC: Room 160

Presentation Authors: Bradley A. Potts*, Danielle J. Degoski, Jillene M. Brooks, Andrew C. Peterson, Durham, NC, Dwight E. Nelson, Thaddeus S. Brink, Minneapolis, MN, Matthew O. Fraser, Durham, NC

Introduction: Sacral neurostimulation (SNS) has most commonly been used as a continuous treatment for urge incontinence,but preclinical and clinical evidence suggest that non-continuous or discrete stimulation periods may also be efficacious. We used our rat model to investigate whether continuous SNS is required for increasing bladder capacity or if therapy temporally targeted to specific phases of the bladder filling cycle show similar responses.

Methods: Urethane anesthetized female Sprague-Dawley rats (n=24) received jugular and transvesical catheters. L6/S1 nerve trunks were isolated bilaterally and fine-wire bipolar electrodes were placed on each and insulated with parafilm and mineral oil. The wounds were closed with suture. Bladder catheters were connected to infusion pumps and pressure transducers. True bladder capacity (TBC) was determined using stable single fill cystometrograms following control continuous cystometry (0.1 ml/min) and prior to every stimulation period. In the first series, we tested the responses to SNS durations that were calculated to cover the initial 25%, 50%, 75%, and 100% of the control filling cycle duration (n=10; all stimulations were initiated at the start of bladder filling). In the second series, we measured responses to SNS over 25% or 50% of the bladder fill cycle, but initiated SNS at 0, 25, 50 or 75% of filling (for 25%) or at 0 or 50% of calculated filling (for 50%). For this test the 25% fills were randomly delivered. Data were analyzed by Friedman Test and Dunn's Multiple Comparisons Test.

Results: In the first series, we observed significant increases in TBC only when SNS was applied for 75 or 100% of the fill cycle duration (30 and 35% increases over controls, resp., p<0.05). In the second series, we observed significant increases in TBC only to SNS delivered beginning at 75 and 100% of total fill (25% duration SNS) and beginning at 50% fill (50% duration SNS; 32 and 43%, resp., p<0.001). Pre-SNS TBC control values did not change in either series.

Conclusions: These data demonstrate that SNS applications timed to occur within the latter phases of bladder filling (e.g. the final 25 or 50% of the bladder fill cycle) appear to be most important for increasing bladder capacity. A clinical strategy utilizing this principle may improve battery life and reduce frequency of reoperation for battery replacement. The results also suggest important physiological differences across the bladder filling phase that should be further explored. Temporal targeting of therapies to these phases of bladder filling may allow improved efficacy or reduced side effects.

Source Of Funding: Medtronic Inc., Minneapolis, Minnesota

Bradley A. Potts

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