Kimura S. et al., 2022: Low-energy shock wave therapy ameliorates ischemic-induced overactive bladder in a rat model.

Thursday, 09 March 2023

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Kimura S, Kawamorita N, Kikuchi Y, Shindo T, Ishizuka Y, Satake Y, Sato T, Izumi H, Yamashita S, Yasuda S, Shimokawa H, Ito A.
Department of Urology, Tohoku University Graduate School of Medicine, 1-Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Graduate School, International University of Health and Welfare, Narita, Japan.

Abstract

This study was to evaluate whether Low-energy shock wave therapy (LESW) improves ischemic-induced overactive bladder in rats and investigate its therapeutic mechanisms. Sixteen-week-old male Sprague–Dawley rats were divided into three groups: arterial injury (AI), AI with LESW (AI-SW), and control groups. LESW was irradiated in AI-SW during 20–23 weeks of age. At 24 weeks of age, conscious cystometry was performed (each n = 8). The voiding interval was shortened in AI (mean ± SEM: 5.1 ± 0.8 min) than in control (17.3 ± 3.0 min), whereas significant improvements were observed in AI-SW (14.9 ± 3.3 min). The bladder blood flow was significantly increased in AI-SW than in AI. Microarray analysis revealed higher gene expression of soluble guanylate cyclase (sGC) α1 and β1 in the bladder of AI-SW compared to AI. Protein expression of sGCα1 and sGCβ1 was higher in AI-SW and control groups than in AI. Cyclic guanosine monophosphate (cGMP) was elevated in AI-SW. As an early genetic response, vascular endothelial growth factor and CD31 were highly expressed 24 h after the first LESW. Suburothelial thinning observed in AI was restored in AI-SW. Activation of sGC-cGMP may play a therapeutic role of LESW in the functional recovery of the bladder.
Sci Rep. 2022 Dec 19;12(1):21960. doi: 10.1038/s41598-022-26292-x. PMID: 36536004. FREE ARTICLE

Comments 1

Jens Rassweiler on Thursday, 09 March 2023 09:30

This is a very interesting article using a specific animal model to prove the positive effects on Li-ESWT on ischemic overactive bladder. chronic pelvic ischemia related to metabolic syndrome is considered to have a preeminent role in causing a storage symptom syndrome, “overactive bladder (OAB),” in the aging population. In recent years, low-energy shock wave therapy (LESW) has become known to be effective in inducing various biological changes including angiogenesis, anti-inflammation, nerve regeneration, cell proliferation, and alteration of membrane permeability. A clinical pilot study for OAB has recently been launched and its outcome has been positive to date.

Using the rat model of ischemic-induced OAB, with a combination of arterial injury and a high-cholesterol sixteen-week-old male Sprague–Dawley rats were divided into three groups
each n = 8): arterial injury (AI), AI with LESW (AI-SW), and control groups. LESW was irradiated in AI-SW during 20–23 weeks of age. Shock wave generator DUOLITH SD1 (Storz Medical, Tägerwilen, Switzerland) was used to give 1800 shots with an intensity of 0.25 mJ/mm2 (total energy flux density) and frequency of 3 Hz. The focused handpiece was manually placed on the lower abdominal wall and animals were anesthetized during the procedure.

At 24 weeks of age, conscious cystometry was performed. The voiding interval was shortened in AI (mean ± SEM: 5.1 ± 0.8 min) than in control (17.3 ± 3.0 min), whereas significant improvements were observed in AI‐SW (14.9 ± 3.3 min). The bladder blood flow was significantly increased in AI‐SW than in AI.
Cyclic guanosine monophosphate (cGMP) was elevated in AI‐SW. As an early genetic response, vascular endothelial growth factor and CD31 were highly expressed 24 h after the first LESW. Suburothelial thinning observed in AI was restored in AI‐SW. Activation of sGC‐cGMP may play a therapeutic role of LESW in the functional recovery of the bladder.

Blood flow was measured in the anterior bladder walls and adjusted by arterial blood pressure. The adjusted blood flow was significantly greater in the control and AI-SW groups than in the AI group at the three points of saline infusion (0, 0.5, and 1.0 ml).

Even though sGC and cGMP could be involved in therapeutic mechanisms of ischemic induced OAB, little has been investigated about the activation of sGC-cGMP with LESW. In contrast, many studies of LESW demonstrated functional recovery of pathophysiology in animal models along with angiogenesis involved with VEGF. Despite lacking definitive evidence of angiogenesis other than the early genetic response of VEGF and CD31 after LESW, the angiogenesis could increase the blood perfusion, then, increased blood perfusion could prevent ischemic-induced degradation of sGC. Activation of eNOS, if it occurs, could also upregulate expression of sGC and cGMP. In the AI-SW model, activated cGMP may also increase peripheral perfusion with vessel dilation creating a virtuous cycle, while the AI model fails to promote cGMP due to a shortage of sGC under chronic ischemia.

These findings indicate, that activation of the sGC-cGMP pathway may play a crucial role in the functional recovery of the bladder and that this could be stimulated by Li-ESWT.

This study will be definitively a good basis for future clinical trials.

Using the rat model of ischemic-induced OAB, with a combination of arterial injury and a high-cholesterol sixteen-week-old male Sprague–Dawley rats were divided into three groups
each n = 8): arterial injury (AI), AI with LESW (AI-SW), and control groups. LESW was irradiated in AI-SW during 20–23 weeks of age. Shock wave generator DUOLITH SD1 (Storz Medical, Tägerwilen, Switzerland) was used to give 1800 shots with an intensity of 0.25 mJ/mm2 (total energy flux density) and frequency of 3 Hz. The focused handpiece was manually placed on the lower abdominal wall and animals were anesthetized during the procedure.

At 24 weeks of age, conscious cystometry was performed.  The voiding interval was shortened in AI (mean ± SEM: 5.1 ± 0.8 min) than in control (17.3 ± 3.0 min), whereas significant improvements were observed in AI‐SW (14.9 ± 3.3 min). The bladder blood flow was significantly increased in AI‐SW than in AI. 
Cyclic guanosine monophosphate (cGMP) was elevated in AI‐SW. As an early genetic response, vascular endothelial growth factor and CD31 were highly expressed 24 h after the first LESW. Suburothelial thinning observed in AI was restored in AI‐SW. Activation of sGC‐cGMP may play a therapeutic role of LESW in the functional recovery of the bladder.

Blood flow was measured in the anterior bladder walls and adjusted by arterial blood pressure. The adjusted blood flow was significantly greater in the control and AI-SW groups than in the AI group at the three points of saline infusion (0, 0.5, and 1.0 ml).

Even though sGC and cGMP could be involved in therapeutic mechanisms of ischemic induced OAB, little has been investigated about the activation of sGC-cGMP with LESW. In contrast, many studies of LESW demonstrated functional recovery of pathophysiology in animal models along with angiogenesis involved with VEGF. Despite lacking definitive evidence of angiogenesis other than the early genetic response of VEGF and CD31 after LESW, the angiogenesis could increase the blood perfusion, then, increased blood perfusion could prevent ischemic-induced degradation of sGC. Activation of eNOS, if it occurs, could also upregulate expression of sGC and cGMP. In the AI-SW model, activated cGMP may also increase peripheral perfusion with vessel dilation creating a virtuous cycle, while the AI model fails to promote cGMP due to a shortage of sGC under chronic ischemia. 
 
These findings indicate, that activation of the sGC-cGMP pathway may play a crucial role in the functional recovery of the bladder and that this could be stimulated by Li-ESWT.

This study will be definitively a good basis for future clinical trials.

This is a very interesting article using a specific animal model to prove the positive effects on Li-ESWT on ischemic overactive bladder. chronic pelvic ischemia related to metabolic syndrome is considered to have a preeminent role in causing a storage symptom syndrome, “overactive bladder (OAB),” in the aging population. In recent years, low-energy shock wave therapy (LESW) has become known to be effective in inducing various biological changes including angiogenesis, anti-inflammation, nerve regeneration, cell proliferation, and alteration of membrane permeability. A clinical pilot study for OAB has recently been launched and its outcome has been positive to date. Using the rat model of ischemic-induced OAB, with a combination of arterial injury and a high-cholesterol sixteen-week-old male Sprague–Dawley rats were divided into three groups each n = 8): arterial injury (AI), AI with LESW (AI-SW), and control groups. LESW was irradiated in AI-SW during 20–23 weeks of age. Shock wave generator DUOLITH SD1 (Storz Medical, Tägerwilen, Switzerland) was used to give 1800 shots with an intensity of 0.25 mJ/mm2 (total energy flux density) and frequency of 3 Hz. The focused handpiece was manually placed on the lower abdominal wall and animals were anesthetized during the procedure. At 24 weeks of age, conscious cystometry was performed. The voiding interval was shortened in AI (mean ± SEM: 5.1 ± 0.8 min) than in control (17.3 ± 3.0 min), whereas significant improvements were observed in AI‐SW (14.9 ± 3.3 min). The bladder blood flow was significantly increased in AI‐SW than in AI. Cyclic guanosine monophosphate (cGMP) was elevated in AI‐SW. As an early genetic response, vascular endothelial growth factor and CD31 were highly expressed 24 h after the first LESW. Suburothelial thinning observed in AI was restored in AI‐SW. Activation of sGC‐cGMP may play a therapeutic role of LESW in the functional recovery of the bladder. Blood flow was measured in the anterior bladder walls and adjusted by arterial blood pressure. The adjusted blood flow was significantly greater in the control and AI-SW groups than in the AI group at the three points of saline infusion (0, 0.5, and 1.0 ml). Even though sGC and cGMP could be involved in therapeutic mechanisms of ischemic induced OAB, little has been investigated about the activation of sGC-cGMP with LESW. In contrast, many studies of LESW demonstrated functional recovery of pathophysiology in animal models along with angiogenesis involved with VEGF. Despite lacking definitive evidence of angiogenesis other than the early genetic response of VEGF and CD31 after LESW, the angiogenesis could increase the blood perfusion, then, increased blood perfusion could prevent ischemic-induced degradation of sGC. Activation of eNOS, if it occurs, could also upregulate expression of sGC and cGMP. In the AI-SW model, activated cGMP may also increase peripheral perfusion with vessel dilation creating a virtuous cycle, while the AI model fails to promote cGMP due to a shortage of sGC under chronic ischemia. These findings indicate, that activation of the sGC-cGMP pathway may play a crucial role in the functional recovery of the bladder and that this could be stimulated by Li-ESWT. This study will be definitively a good basis for future clinical trials.

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