Monitoring of erectile and urethral sphincter dysfunctions in a rat model mimicking radical prostatectomy damage.
BACKGROUND
Animal models of urinary incontinence and erectile dysfunction following radical prostatectomy (RP) are lacking.


OBJECTIVE
To develop an animal model of combined post-RP urethral sphincter and erectile dysfunctions, and noninvasive methods to assess erectile function (EF) and urinary sphincter function (USF) during prolonged follow-up.


METHODS
In the main experiments, 60 male Sprague Dawley rats were randomized to a sham operation (N = 30) or electrocautery of both sides of the striated urethral sphincter (N = 30). EF and USF were evaluated preoperatively and on postoperative days 7, 15, 30, 60, and 90. Sphincter and penile tissue samples were evaluated histologically on days 7 (N = 10) and 30 (N = 10) to detect apoptosis (TUNEL assays) and fibrosis (Trichrome Masson staining).


METHODS
To assess EF, we measured systemic and penile blood flow using penile laser Doppler and penile rigidity using a durometer before and after apomorphine injection. USF was assessed based on the retrograde leak point pressure (LPPr).


RESULTS
Apomorphine increased baseline Doppler flow by 180% (95% confidence interval, 156-202%) and penile hardness from 3.49 ± 0.5 to 7.16 ± 0.82 Shore A units but did not change systemic arterial flow. Mean LPPr was 76.8 ± 6.18 mm Hg at baseline and decreased by 50% after injury, with no response to apomorphine on day 7. EF and USF impairments persisted up to 90 days post injury. Histology showed penile apoptosis on day 7 and extensive urethral sphincter and penile fibrosis on day 30. Our data did not allow us to determine whether the impairment in erectile response to apomorphine preponderantly reflected arterial penile insufficiency or veno-occlusive dysfunction.


CONCLUSIONS
Electrocautery of the striated urethral sphincter caused severe and lasting impairment of EF and USF that could be monitored repeatedly using minimally invasive methods. This new animal model may hold potential for developing new treatments designed to correct post-RP impairments.
APHP, Urology Department and CRCDC, Hospital Henri Mondor, Créteil, France.
Muhieddine
M
Khodari
Rachid
R
Souktani
Olivier
O
Le Coz
Dina
D
Bedretdinova
Florence
F
Figeac
Adrien
A
Acquistapace
Pierre Francois
PF
Lesault
Julie
J
Cognet
Anne Marie
AM
Rodriguez
René
R
Yiou
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D018783:Impotence, Vasculogenic / Q000503:physiopathology*; D008297:Male; D010410:Penile Erection / Q000502:physiology; D011183:Postoperative Complications / Q000503:physiopathology*; D011468:Prostatectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014521:Urethra / Q000503:physiopathology*; D014549:Urinary Incontinence / Q000503:physiopathology*; D014563:Urodynamics / Q000502:physiology