Urodynamic Characterization of Aged Ossabaw Miniature Pigs Mimics Human Detrusor Underactivity

Abstract

Detrusor underactivity (DU) and its clinical correlate, underactive bladder (UAB), are common urologic conditions experienced by up to 20 million Americans, however, its pathophysiology is poorly understood and treatment is limited. This highlights the need for a high fidelity animal model that has similar bladder characteristics that will allow direct testing of new treatment modalities. Building on our previous study in metabolic syndrome pigs (Comp. Med. PMID 32972487), we hope to further establish the Ossabaw swine as a translational model for human bladder dysfunction, highlighting its comparable bladder capacity and function as major strengths. We hypothesized that the aged Ossabaw model will demonstrate detrusor underactivity on urodynamic measures due to similar age-related loss of bladder contractility and degeneration of neural and non-neural function. Ossabaw pigs were catheterized via transurethral access when possible or suprapubic cystostomy under general anesthesia. Urodynamic studies were conducted on old (N=3; 10.7 ± 2.6 y) and young (N=10; 3.2 ± 1.0 y) pigs to confirm detrusor underactivity. Fisher's exact test and two sample t-test were performed for comparisons between demographic and urodynamic parameters. Intravesical pressure at capacity with saline was significantly reduced in old vs. young pigs (6.4 ± 3.5 vs. 27.2 ± 17.5 cm H2O; p < 0.001), while compliance was significantly increased (201.4 ± 120.9 vs. 74.6 ± 73.4 mL/cm H2O; p = 0.03). Carbachol infusion revealed significantly reduced maximal pressure during active contraction in aged pigs (29.1 ± 4.0 vs. 44.5 ± 16.7; p = 0.03), but no significant changes in compliance. This characteristic hallmark of detrusor underactivity in aged Ossabaw miniature swine demonstrates its powerful utility as a translational model for age-related bladder dysfunction due to its human-sized bladder more closely approximating human urinary physiology.