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INVESTIGATIVE
UROLOGY
Penile
weight and cell subtype specific changes in a post-radical prostatectomy
model of erectile dysfunction
User HM, Hairston JH, Zelner DJ, McKenna KE, McVary KT
From the Departments of Urology and Physiology, Northwestern University
Medical School, Chicago, Illinois
J Urol. 2003; 169:1175-9
- Purpose:
We evaluated neurogenic erectile dysfunction, focusing on the post-radical
prostatectomy model. We investigated changes in DNA, protein and apoptotic
cells of the rat penis after denervation. Gross morphometry was measured
to elucidate the impact of chemical changes.
- Materials
and Methods:
Postpubertal male Sprague-Dawley rats were randomized to bilateral or
unilateral cavernous nerve transection, or sham operation. Wet weight,
DNA content and protein content were measured. Tissue sections were
stained for apoptosis by terminal deoxynucleotidyl transferase-mediated
deoxyuridine triphosphate nick end labeling and the apoptotic index
was calculated. Dual staining was performed for endothelial and smooth
muscle cells to identify apoptotic cells.
- Results:
Penile wet weight was significantly decreased at all time points after
bilateral neurotomy (p<0.0005). Unilateral neurotomy allowed much
greater preservation of penile weight. DNA content was significantly
decreased in bilaterally denervated penes and unchanged in unilaterally
operated penes. Protein content was not significantly altered in the
bilateral or unilateral cohorts. Bilateral neurotomy induced significant
apoptosis, while unilateral surgery caused significantly less apoptosis.
Each population had apoptotic clustering just beneath the tunica albuginea,
which was mostly smooth muscle cells.
- Conclusions:
These
data suggest the importance of neural integrity to maintain penile homeostasis.
The loss in penile weight was consistent with the anecdotal experience
of many clinicians. Decreased DNA content may have been due to significant
levels of apoptosis in smooth muscle cells. Preserved protein content
may suggest an increase in extracellular protein, as postulated in corporeal
fibrosis. The subtunical population of apoptotic smooth muscle cells
revealed a mechanism for veno-occlusive dysfunction observed after radical
prostatectomy. These effects were significantly moderated in the unilateral
model, reinforcing the critical nature of neural integrity.
- Editorial
Comment
This is a sophisticated study of the detrimental effects of dennervation
on penile function and structure, with clinical applications for further
understanding the erectile dysfunction following radical prostatectomy.
This is the first study which clearly demonstrated that lesion to the
cavernous nerves will result in immediate beginning of apoptosis, primarily
in smooth muscle cells. Also, the reductions in smooth muscle cells,
mainly in the subtunical position, would explain the significant occurrence
of veno-occlusive dysfunction in post-radical prostatectomy erectile
dysfunction. Also, the present study demonstrated a dramatically reduction
in the penile weight when bilateral cavernous nerve injury was created.
On the other hand, these changes were significantly reduced with preservation
of one neurovascular bundles. The authors found that the DNA content
remained intact in the unilateral neural lesion, while it altered dramatically
in the bilateral model of lesion. These findings reinforced the idea
for the clinician, to make all efforts for preserving the neurovascular
bundles, at least in one side, during radical prostatectomy.
Dr.
Francisco J.B. Sampaio
Chairman, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil
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