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Lee YC. et al., 2021: Therapeutic effect of Low intensity Extracorporeal Shock Wave Therapy (Li-ESWT) on diabetic bladder dysfunction in a rat model

Lee YC, Hsieh TJ, Tang FH, Jhan JH, Lin KL, Juan YS, Wang HS, Long CY.
Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Urology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Obstetrics and Gynecology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Obstetrics and Gynecology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Abstract

Objectives: Low intensity extracorporeal shock wave therapy (Li-ESWT) has proven to be effective and safe for the treatment of various urological disorders including erectile dysfunction and chronic pelvic pain syndrome. In this study, we elucidated the therapeutic effect and possible mechanisms of Li-ESWT on diabetic bladder dysfunction (DBD) in a rat model.

Materials and Methods: In all, thirty-two female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus (DM) control, and DM Li-ESWT. The two DM groups were given high fat diets for one month, followed by 2 intraperitoneal injections of streptozotocin (STZ) 30 mg/kg separated by one week. Body weight and fasting blood glucose were monitored every week. Only rats with fasting blood glucose 140 mg/dL or more were considered diabetic and used in the subsequent portions of the study. The Li-ESWTs were applied toward the pelvis of the rats twice a week for 4 weeks with energy flux density (EFD) 0.02 mJ/mm2, 500 shocks, at 3Hz. All rats underwent plasma insulin tolerance test, conscious cystometry, leak-point pressure (LPP) assessment, and immunohistochemical studies.

Results: DM groups had significantly lower insulin sensitivity and higher body weight. Conscious cystometry also revealed voiding dysfunctions. In the DM Li-ESWT group, the rats had significantly improved voiding functions that were reflected in longer micturition intervals and higher LPP compared to DM control. Immunofluorescence in DM control groups showed increased tyrosine hydroxylase (TH) expression and decreased neuronal nitric oxide synthase (nNOS) expression in the longitudinal urethral smooth muscles. Besides, rats had dilations and deformities of suburothelium capillary network of the bladder, revealing the deterioration of the nerve function of the urethra and destruction of the vascularization of the bladder. However, the DM Li-ESWT group exhibited recovery of the nerve expression of the urethra and vascularization of bladder.

Conclusions: Li-ESWT ameliorates the bladder dysfunction and urinary continence in the DBD rat model, reflected in restoration of the nerve expression of the urethra and the vascularization of the bladder. Non-invasive Li-ESWT could be an alternative therapeutic option for DBD.

Int J Med Sci. 2021 Jan 29;18(6):1423-1431. doi: 10.7150/ijms.55274. eCollection 2021. PMID: 33628099. FREE ARTICLE

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Comments 1

Peter Alken on Wednesday, 09 June 2021 10:15

The only objection I have to the study is that both, the induction of the diabetes and the ESWT were acute experiments not comparable to the development of diabetogenic effects seen in humans. The average life expectancy of a rat is 2 years. In other words, one rat year may be comparable to 35 human years. The duration of the whole experiment was 13 weeks and that of the diabetes induction was 6 weeks what could be translated to ~ 9 and 4 human years resp. Even this is a relatively short time. However, the model used in the experiments is well established.
Looking at data in a publication I may accept that 0 of 10 is 0% but I feel uncomfortable if like in the present study 8 of 9 and 7 of 12 are expressed as 88,9% and 58,3% resp. and are used to prove statistically significant differences. The control animals were also treated with Li-ESWT. I would expect control animals to be without any intervention.
A conclusion can be drawn when clinical application hopefully confirms that “Non-invasive Li-ESWT could be an alternative therapeutic option for DBD.”

Peter Alken

The only objection I have to the study is that both, the induction of the diabetes and the ESWT were acute experiments not comparable to the development of diabetogenic effects seen in humans. The average life expectancy of a rat is 2 years. In other words, one rat year may be comparable to 35 human years. The duration of the whole experiment was 13 weeks and that of the diabetes induction was 6 weeks what could be translated to ~ 9 and 4 human years resp. Even this is a relatively short time. However, the model used in the experiments is well established. Looking at data in a publication I may accept that 0 of 10 is 0% but I feel uncomfortable if like in the present study 8 of 9 and 7 of 12 are expressed as 88,9% and 58,3% resp. and are used to prove statistically significant differences. The control animals were also treated with Li-ESWT. I would expect control animals to be without any intervention. A conclusion can be drawn when clinical application hopefully confirms that “Non-invasive Li-ESWT could be an alternative therapeutic option for DBD.” Peter Alken
Friday, 29 March 2024