Modern aspects of pathophysiology and prevention of erectile dysfunction and cavernous fibrosis after radical prostatectomy


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Abstract

Partial denervation of cavernous tissue (CT) during nerve sparing radical prostatectomy (RPE) can cause development of neuropraxy and cavernous fibrosis (CF) resulting in erectile dysfunction (ED) after operation. We investigated the impact of intracavernous nitric oxide donor therapy on cavernous tissue after denervation in rats. Twenty six adult male Wistar rats were divided into three groups. Bilateral cavernous nerves (CN) crashing was made in ten rats (group 1). Ten underwent bilateral CN crashing with intra- and postoperative (2 times a week) intracavernous injection with new nitric oxide donor dinitrosyl iron complex (DNIC) in a dose 0.5 mmol/l (group 2). The latter six underwent sham operation (a control group). We evaluated CT changes by electrone microscopy (cells in the field of vision - CFV) and immunohistochemistry 3 and 6 months after the operation. CT denervation in group 1 led to a significant decline in mitotic activity of smooth muscle cells (1.79 ± 0.04 and 1.14 ± 0.03 CFV), in stimulation of endothelium and fibroblasts proliferation activity (3.14 ± 0.07 and 5.17 ± 0.11 CFV, 6.19 ± 0.97 and 8.21 ± 1.13 CFV, respectively) 3 and 6 month after operation. In the control group mitotic, endothelium and fibroblasts proliferation was 2.01 ± 0.06; 1.07 ± 0.01 and 4.18 ± 0.22 CFV, respectively. The greatest changes were in smooth muscle cells (SMC). We found synthetic activity of collagenase in SMC 3 (5.18 ± 0.64 CFV) and especially six (6.18 ± 1.19 CFV) months after CN crashing. Some of SMC had round or star-shaped forms which are common for fibroblasts. There were abnormalities of contact braking of the cellular layer and appearance of chaps between the endothelium. As a result, some cells were climbing and creeping onto neighbor cells causing changes in configuration of endothelial monolayer. Nitric oxide replacement therapy using DNIC prevented morphological changes of all types of cells in CT. We registered stabilization of endothelial (1.97 ± 0.07 and 1.74 ± 0.05 CFV) and fibroblast (3.97 ± 0.11 and 4.01 ± 0.17 CFV) proliferation and improvement of SMC mitotic activity (2.56 ± 0.09 and 2.34 ± 0.12 CFV) three and six months after operation. Synthetic activity of collagenase in SMC was 0.47 ± 0.01 DFV and was absent 3 and 6 months after CN crashing, respectively. These results show that restoration of a nitric oxide level in the penis can prevent development of cavernous fibrosis after CN injury and that DNIC has a significant potential for penile rehabilitation and treatment of ED after RPE.

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