Effects of Next-Generation Low-Energy Extracorporeal Shockwave Therapy on Erectile Dysfunction in an Animal Model of Diabetes

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Abstract

Purpose

Gene therapy, stem cell therapy, and low-energy extracorporeal shockwave therapy (ESWT) have been investigated as treatments for refractory erectile dysfunction (ED), but inconclusive evidence has been obtained. We investigated the effect of a next-generation electromagnetic cylinder ESWT device on an animal model of ED.

Materials and Methods

Diabetes mellitus (DM)-induced rats were divided into 3 groups: group 1, control; group 2, DM; and group 3, DM+ESWT. Rats were treated with ESWT 3 times a week for 2 weeks. After the treatment course, intracavernous pressure was measured and the corpus cavernosum and cavernous nerve were evaluated.

Results

In the DM group, all parameters predicted to be significantly lower in the ED model had statistically significantly decreased (p<0.01). As a measurement of erectile function, intracavernous pressure was evaluated. The DM+ESWT group exhibited significantly restored erectile function compared to the DM group (p<0.05). Moreover, ESWT treatment restored smooth muscle content, as assessed by Masson's trichrome staining (p<0.05). Finally, corporal tissue and the dorsal nerve were evaluated by immunohistochemistry, Western blotting, and ELISA. After ESWT treatment, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, cyclic guanosine monophosphate, and neuronal nitric oxide synthase (nNOS) expression levels were restored to levels in the DM group (p<0.05).

Conclusions

Electromagnetic cylinder ESWT device resulted in increased VEGF, nNOS, and eNOS expression; reduced smooth muscle atrophy; and increased endothelial cell regeneration in a DM-associated ED model. Our data suggest that safe and effective application could be possible in future clinical studies.

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Most cited references 23

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Diabetes-induced erectile dysfunction: epidemiology, pathophysiology and management.

Vrushali Thorve, Ajay Kshirsagar, Neeraj Vyawahare … (2011)

Erectile dysfunction (ED) is defined as the inability of the male to attain and maintain erection of penis sufficient to permit satisfactory sexual intercourse. Prevalence of impotence in diabetic men is ≥50%. The pathophysiology of diabetes-induced erectile dysfunction (DIED) is multifactorial and no single etiology is at the forefront. The proposed mechanisms of erectile dysfunction in diabetic patients includes elevated advanced glycation end-products, increased levels of oxygen free radicals, impaired nitric oxide synthesis, increased endothelin B receptor binding sites and up-regulated RhoA/Rho-kinase pathway, neuropathic damage and impaired cyclic guanosine monophosphate (cGMP)-dependent protein kinase-1. The treatment of DIED is multimodal. Treatment of the underlying hyperglycemia and comorbidities is of utmost importance to prevent or halt the progression of disease. Oral medications are considered as the first line therapy for management of DIED. If oral agents cannot be used or have insufficient efficacy despite appropriate dosing and education, second-line treatments should be addressed. When there is lack of efficacy or when there is dissatisfaction with other modalities, penile prostheses are often the best alternative for ED and are considered as the third line therapy for DIED. Future strategies in the evolution of the treatment of DIED are aimed at correcting or treating the underlying mechanisms of DIED. Copyright © 2011 Elsevier Inc. All rights reserved.

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Health-related quality of life in men with erectile dysfunction.

Nadeem Dhanani, Robert J Nied, Kevin M. Litwin (1998)

To assess health-related quality of life (HRQOL) in men with erectile dysfunction. Descriptive survey with general and disease-specific measures. The instrument contained three established, validated HRQOL measures, a validated comorbidity checklist, and sociodemographics. The RAND 36-Item Health Survey 1.0 (SF-36) was used to assess general HRQOL. Sexual function and sexual bother were assessed using the UCLA Prostate Cancer Index. The marital interaction scale from the Cancer Rehabilitation Evaluation System Short Form (CARES-SF) was used to assess each patient's relationship with his sexual partner. Urology clinics at a university medical center and the affiliated Veterans Affairs (VA) Medical Center. Thirty-five (67%) of 54 consecutive university patients presenting for erectile dysfunction and 22 (42%) of 52 VA patients who were awaiting a previously prescribed vacuum erection device participated. The university respondents scored slightly lower than population normals in social function, role limitations due to emotional problems, and emotional well-being. The VA respondents scored lower than expected in all eight domains. Scores for the VA population were significantly lower than those for the university population in physical function, role limitations due to physical problems, bodily pain, and social function. A significant correlation was seen between marital interaction and sexual function (r = -.33, p = .01) but not between marital interaction and sexual bother (r = -.15, p = .26) in the total sample. Sexual function also correlated significantly with general health perceptions (r = .34, p = .01), role limitations due to physical problems (r = .29, p = .03), and role limitations due to emotional problems (r = .30, p = .03). Sexual bother did not correlate with any of the general HRQOL domains. Affluent men reported better sexual function (p = .03). The emotional domains of the SF-36 are associated with more profound impairment than are the physical domains in men with erectile dysfunction. Erectile dysfunction and the bother it causes are discrete domains of HRQOL and distinct from each other in these patients. With increased attention to patient-centered medical outcomes, greater emphasis has been placed on such variables as HRQOL. This should be particularly true for a patient-driven symptom, such as erectile dysfunction.

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Stem cell therapy for erectile dysfunction: a critical review.

Ching-Po Lin, Yun Huang, Chunhua Deng … (2012)

Erectile dysfunction (ED) is a prevailing health problem that seriously impacts quality of life. Current treatment options are less effective for patients having cavernous nerve (CN) injury or diabetes mellitus-related ED. These 2 types of ED are thus the main focus of past and current stem cell (SC) therapy studies. In a total of 16 studies so far, rats were exclusively used as disease models and SCs were mostly derived from bone marrow, adipose tissue, or skeletal muscle. For tracking, SCs were labeled with LacZ, green fluorescent protein, 4',6-diamidino-2-phenylindole, DiI, bromodeoxyuridine, or 5-ethynyl-2-deoxyuridine, some of which might have led to data misinterpretation. SC transplantation was done exclusively by intracavernous (IC) injection, which has been recently shown to have systemic effects. Functional assessment was done exclusively by measuring increases of IC pressure during electrostimulation of CN. Histological assessment usually focused on endothelial, smooth muscle, and CN contents in the penis. In general, favorable outcomes have been obtained in all trials so far, although whether SCs had differentiated into specific cell lineages remains controversial. Recent studies have shown that intracavernously injected SCs rapidly escaped the penis and homed into bone marrow. This could perhaps explain why intracavernously injected SCs had systemic antidiabetic effects and prolonged anti-ED effects. These hypotheses and the differentiation-versus-paracrine debate require further investigation.

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Author and article information

Journal

Journal ID (nlm-ta): World J Mens Health

Journal ID (iso-abbrev): World J Mens Health

Journal ID (publisher-id): WJMH

Title: The World Journal of Men's Health

Publisher: Korean Society for Sexual Medicine and Andrology

ISSN (Print): 2287-4208

ISSN (Electronic): 2287-4690

Publication date (Print): December 2017

Publication date (Electronic): 20 November 2017

Volume: 35

Issue: 3

Pages: 186-195

Affiliations

[1 ]Department of Urology, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, Korea.

[2 ]Department of Urology, The Catholic University of Korea, Incheon St. Mary's Hospital, Incheon, Korea.

[3 ]Catholic Integrative Medicine Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.

[4 ]Department of Urology, Korea University College of Medicine, Seoul, Korea.

Author notes

Correspondence to: Sae Woong Kim. Department of Urology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. Tel: +82-2-2258-6226, Fax: +82-2-599-7839, ksw1227@ 123456catholic.ac.kr

Author information

Hyun Cheol Jeong https://orcid.org/0000-0001-8846-1351

Seung Hwan Jeon https://orcid.org/0000-0001-6695-6097

Zhu Guan Qun https://orcid.org/0000-0001-7841-8026

Kang Sup Kim https://orcid.org/0000-0002-9534-7829

Sae Woong Choi https://orcid.org/0000-0002-3829-939X

Fahad Bashraheel https://orcid.org/0000-0002-1969-7720

Woong Jin Bae https://orcid.org/0000-0001-7703-1161

Su Jin Kim https://orcid.org/0000-0002-1917-2780

Hyuk Jin Cho https://orcid.org/0000-0003-2599-2950

U-Syn Ha https://orcid.org/0000-0001-9930-0588

Sung Hoo Hong https://orcid.org/0000-0002-1952-4010

Ji Youl Lee https://orcid.org/0000-0001-6775-1157

Du Geon Moon https://orcid.org/0000-0002-9031-9845

Sae Woong Kim https://orcid.org/0000-0002-9127-9400

Article

DOI: 10.5534/wjmh.17024

PMC ID: 5746490

PubMed ID: 29164834

SO-VID: 3b66c2ec-e75f-48ba-99be-5224988a6998

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 05 July 2017

Date revision received : 25 August 2017

Date accepted : 13 September 2017

Funding

Funded by: Korea Health Industry Development Institute, CrossRef http://dx.doi.org/10.13039/501100003710;

Effects of Next-Generation Low-Energy Extracorporeal Shockwave Therapy on Erectile Dysfunction in an Animal Model of Diabetes

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Abstract

Purpose

Materials and Methods

Results

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Animal Welfare

Most cited references 23

Diabetes-induced erectile dysfunction: epidemiology, pathophysiology and management.

Health-related quality of life in men with erectile dysfunction.

Stem cell therapy for erectile dysfunction: a critical review.

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