Login to Access Video or Poster Abstract: MP82-06
Sources of Funding: 4K12DK100024-04

Introduction

Detrusor underactivity (DUA) is an understudied health concern that affects up to 45% of men and women in secondary care. The clinical management of DUA is inadequate and fails to improve the quality of life of these patients. The limited availability of animal models that exhibit the integrated pathophysiology of DUA impedes the development of new therapeutic approaches. The current studies characterized the bladder function of an obesity model of DUA to increase our understanding of the initiation and progression of urinary retention.

Methods

Animals: Eight-week old female obese-prone (OP) and obese-resistant (OR) rats purchased from Charles River (Boston, MA) were housed two per cage and maintained in standard laboratory conditions with food and water available ad libitum. Experimental procedures were approved by the Duke University IACUC and experimentation was conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals (8th ed.)._x000D_ High-fat feeding and glucose measurements: OP and OR rats were fed a 45% fat diet (D12451, Research Diets, Inc.) from 9-21 weeks and a 60% fat diet (D12492, Research Diets, Inc.) from 21-24 weeks. Whole blood was collected from the tail vein for glucose analysis at 8 and 24 weeks._x000D_ Surgical preparation and instrumentation: At 24 weeks, OP and OR rats were anesthetized with urethane (1.2 g/kg s.c. and supplemented as needed). The bladder was exposed through a midline abdominal incision and a flared PE-60 catheter was inserted into the bladder dome. The catheter was secured and connected via a 3-way stopcock to a pressure transducer and infusion pump. A paddle with platinum iridium contacts was placed between the pubic symphysis and the EUS to record EMG signals. Pressure and EMG signals were amplified, filtered, and sampled on a PowerLab acquisition unit with LabChart 7 Pro._x000D_

Results

OP rats weighed significantly more than OR rats (450 ± 11.1 vs. 270 ± 6.7 g, respectively; p ≤ 0.001); however, blood glucose was not altered between OP (169.1 ± 7.11 mg/dl) or OR (176.5 ± 6.09 mg/dl; p ≥ 0.05) rats. Compared to OR rats, OP rats have significantly increased volume threshold (0.7574 ± 0.07 vs. 0.529 ± 0.04 ml; p ≤ 0.05), decreased maximum micturition pressure (16.62 ± 1.2 vs. 23.94 ± 1.1 cmH2O; p ≤ 0.001), and decreased voiding efficiency (8.743 ± 2.58 vs. 42.19 ± 6.5 %; p ≤ 0.001).

Conclusions

OP rats exhibit DUA and decreased voiding efficiency. This animal model may be used to understand the pathophysiology underlying DUA and enable the development of novel therapeutic approaches to recover efficient voiding.

Funding

4K12DK100024-04