Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction

Podlasek, Carol A.; Gonzalez, Christopher; Zelner, David J.; Jiang, Hong Bin; McKenna, Kevin E.; McVary, Kevin T.

doi:10.1038/sj.ijir.3900772

Cited by 61 publications

(48 citation statements)

References 34 publications

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“…Therefore, the high expression of TGF-b1 detected in this study must be the result of permanent penile flaccidity after cavernosal neurectomy which caused a low partial oxygen pressure and hypoxia in the cavernosal sinuses of rats. Another potential factor might be a decrease in nitric oxide synthase-positive nerve fibres responsible for relaxing some minor arteries in the corpus cavernosum after denervation [15,16].…”

Section: Discussionmentioning

confidence: 99%

Expression of transforming growth factor‐β1 in penile tissue from rats with bilateral cavernosal nerve ablation

et al. 2004

BJU International

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OBJECTIVETo explore the expression of transforming growth factor‐β1 (TGF‐β1) in penile tissue from rats after bilateral cavernosal nerve (CN) ablation, mimicking patients who have had no nerve‐sparing during prostatectomy.MATERIALS AND METHODSTen adult male rats (neurectomy group) had a bilateral CN resection aseptically under an operating microscope, with six sham‐operated rats as controls. Fifteen weeks after surgery an apomorphine test was used in all rats to assess penile erection. The penile specimens were then collected and prepared for detecting the expression of TGF‐β1 by reverse transcription‐polymerase chain reaction (RT‐PCR), western blot and immunohistochemistry, and for quantitative analysis of the ratio of smooth muscle to collagen fibres in the corpus cavernosum with confocal microscopy.RESULTSAll rats in the sham‐operated group but none after neurectomy had an erectile response after subcutaneous injection with apomorphine (100 µg/kg). Immunohistochemistry, RT‐PCR and western blot analyses showed a significantly higher expression of TGF‐β1 in the penile tissues after neurectomy than after sham surgery. Smooth muscle cells (fluorescing red) and collagen fibres (green autofluorescence) after paraformaldehyde fixation, were clearly identified by confocal microscopy. The fluorescence intensity expressed as the mean (sem) ratio of smooth muscle to collagen fibres in the corpus cavernosum after neurectomy was 0.265 (0.125), significantly lower than that in the sham‐operated group, at 0.760 (0.196) (P < 0.01).CONCLUSIONAn increased expression of TGF‐β1 in penile tissue which promotes the synthesis of collagen may be one of the important factors for the erectile dysfunction caused by bilateral CN ablation. Similar pathophysiological processes may occur in the corpus cavernosum of patients after radical prostatectomy.

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Section: Discussionmentioning

confidence: 99%

Expression of transforming growth factor‐β1 in penile tissue from rats with bilateral cavernosal nerve ablation

et al. 2004

BJU International

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“…20 Decreased smooth muscle tissue is accompanied by increased collagen type I and III deposition in rats after bilateral neurectomy and in men after RP. 21,22 It is possible that corporal smooth muscle apoptosis and increased collagen deposition seen in the rat nerve-crush model may also be present in human patients recovering from RP. This may be associated with the time-dependent increase in the incidence of venous leak found in patients as they recover from RP.…”

Section: Pathophysiologymentioning

confidence: 99%

The role of vacuum erection devices in penile rehabilitation after radical prostatectomy

Lehrfeld

Lee

2009

Int J Impot Res

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Even nerve-sparing radical prostatectomy damages the cavernous nerves and leads to temporary erectile dysfunction (ED) in men recovering from prostate cancer surgery. Historically, patients recovering from prostate cancer surgery have been advised that the return of erectile function (EF) can take from 6 to 18 months, or even longer. Unfortunately, the return of sexual function in these patients remains variable, but is generally thought to be dependent on the individual patient's pre-surgery EF, as well as the degree of cavernous nerve disruption during prostate removal. Recently, there has been a growing movement to proactively treat patients postoperatively for presumed nerve damage to stimulate nerve recovery and possibly reduce the degree of irreversible damage. This would reduce the on-demand therapy these patients would require, and hopefully remove the requirement for an implantable prosthesis. The underlying hypothesis is that the artificial induction of erections shortly after surgery facilitates tissue oxygenation, reducing cavernosal fibrosis in the absence of nocturnal erections, potentially increasing the likelihood of preserving EF. Vacuum erection devices (VED), because of their ability to draw blood into the penis regardless of nerve disturbance, have become the centerpiece of penile rehabilitation protocols. This review will discuss the pathophysiology of radical prostatectomy induced ED and the rationale for rehabilitation. It will then discuss current protocols, including those involving the VED.

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“…11,25 In a rat model, User and colleagues 17 found that apoptotic cells were smooth muscle cells and not endothelial cells, with cell death noted to peak at 2 days after bilateral neurectomy, suggesting early smooth muscle cell dysfunction as a mechanism for the previously observed veno-occlusive dysfunction. 26 McVary 27 has shown that both intrinsic and extrinsic apoptotic pathways were activated in rats whose cavernous nerves were disrupted.…”

Section: Introductionmentioning

confidence: 99%

Penile rehabilitation following treatment for prostate cancer: an analysis of the current state of the art

Al-Shaiji

Domes

Brock

2013

CUAJ

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Despite recent advances in surgical technique using laparoscopic and robotic approaches for the management of early organconfined prostate cancer, most contemporary reports demonstrate significant rates of erectile dysfunction comparable to standard open approaches. Controversy remains related to many of the preand postoperative management strategies, including agents to enhance nerve recovery, erectogenic drugs, antioxidants, vasoactive injectables, vacuum erection devices and nerve grafting procedures. Additionally, the optimal timing of these interventions and their duration, dose, frequency and outcome thresholds remain ill-defined. In our paper, we provide a comprehensive literature review involving both the basic and clinical data surrounding rehabilitative approaches. RésuméMalgré des avancées récentes dans les techniques chirurgicales utilisant la laparoscopie et la robotique pour la prise en charge du cancer de la prostate au stade précoce, la majorité des rapports récents font état de taux significatifs de dysfonction érectile se comparant aux taux associés aux approches ouvertes standard. Bon nombre des stratégies de traitement préopératoires et postopératoires, comme les agents favorisant la récupération nerveuse, les médicaments érec-togènes, les antioxydants, les agents vasoactifs injectables, les pompes péniennes et les greffes de nerfs, font toujours l'objet de controverses. Par ailleurs, le moment optimal pour effectuer ces interventions, la durée de ces dernières, la dose, la fréquence et le seuil d'évaluation des résultats demeurent encore bien mal défi-nis. Cet article de synthèse présente une revue approfondie de la littérature comprenant les données de recherche fondamentale et les données cliniques concernant les approches de réadaptation.going surgery and are thus expressing concern about preservation of erectile function after the procedure, a fact that is true for older men as well. Since Walsh and Donker 4 published their landmark article describing the etiology and prevention of impotence following retropubic RP in 1982, the nerve-sparing technique they described is widely employed and believed to improve postoperative erectile function. 5 Furthermore, there continue to be modifications to the nervesparing technique in an attempt to minimize nerve compromise and improve postoperative potency, as reported by Chuang and coauthors 6 and Masterson and colleagues. 7 However, optimal sexual functioning often requires 18 to 42 months to return, even among men in whom bilateral nerve sparing was performed, with reported recovery rates varying from 16% to 86%. 8,9 Sexual dysfunction has been reported to be an independent determinant of a poorer general health-related quality of life at 2 years after primary treatment for prostate cancer. 10 Recent advances in the understanding of the pathophysiology of postprostatectomy erectile dysfunction (PED) have stimulated great attention directed toward the concept of penile rehabilitation, in which prophylactic measures are instituted to prom...

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Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction

Cited by 61 publications

References 34 publications

Expression of transforming growth factor‐β1 in penile tissue from rats with bilateral cavernosal nerve ablation

Expression of transforming growth factor‐β1 in penile tissue from rats with bilateral cavernosal nerve ablation

The role of vacuum erection devices in penile rehabilitation after radical prostatectomy

Penile rehabilitation following treatment for prostate cancer: an analysis of the current state of the art

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