Saager Tilak Chawla et al., 2024: Radial Type Low-Intensity Extracorporeal Shockwave Therapy Enhances Penile Microvascular Perfusion in an Aging Rat Model: A Novel Interventional Strategy to Treat Erectile Dysfunction

Wednesday, 11 September 2024

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Saager Tilak Chawla 1 , Jad Shahan 1 , Nolan Soutipan 1 , Samuel Ryan Sorkhi 1 , Yong Sun Choi 2 , Woong Jin Bae 2 3 , Sae Woong Kim 2 3 4 , Tung-Chin Hsieh 5 , Mahadevan Raj Rajasekaran 1 6
1Department of Research Service, San Diego VA Healthcare System, San Diego, CA, USA.
2Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
3Catholic Integrative Medicine Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
4Green Medicine Co., Ltd, Busan, Korea.
5Department of Urology, University of California, San Diego, CA, USA.
6Department of Urology, University of California, San Diego, CA, USA.

Abstract

Purpose: Physiological aging is associated with microvascular dysfunction, including in the penis, and this may contribute to age-related erectile dysfunction (ED). Low-intensity extracorporeal shockwave therapy (Li-ESWT) is a non-invasive intervention for ED, but its effect on penile microvascular function, remains unclear. Our objectives are to (i) evaluate the effect of Li-ESWT (specifically radial type ESWT [rESWT]) on penile microvascular perfusion (PMP) in aging rats, (ii) elucidate a possible mechanism, and (iii) evaluate its impact on angiogenic and smooth muscle biomarkers in cavernosal tissue.

Materials and methods: Male rats (n=9; 15-18 months) were anesthetized and subjected to rESWT while monitoring PMP. The nitric oxide (NO) pathway involvement was assessed by measuring the effect of rESWT on PMP following an intracavernosal injection of N(G)-nitroarginine methyl ester (L-NAME) (NO synthase inhibitor). To elucidate the cellular mechanism, another group of rats received repeated rESWT (n=4) or no treatment (n=4) three times/week for two weeks. Rats were euthanized at the end of the study and penile tissues were analyzed for angiogenic markers (vascular endothelial growth factor-A [VEGF-A], endothelial nitric oxide synthase [eNOS]) and smooth muscle content (α-actin) using immunostaining, Western blot, and quantitative polymerase chain reaction (qPCR).

Results: rESWT resulted in more than a 2-fold increase in PMP (from 68.5 arbitrary units; 163.7 AU). L-NAME injection produced a <40%-50% decrease (185.3 to 101.0 AU) in rESWT-induced PMP response. Immunostaining revealed increased α-actin, eNOS, and VEGF-A in the cavernosum and these findings were confirmed by qPCR and Western blot results.

Conclusions: rESWT improved PMP, which may be mediated via increased VEGF expression, which stimulates the NO/cyclic guanosine monophosphate pathway, resulting in sustained PMP. rESWT devices could offer a safe, non-invasive treatment for age-related ED.

World J Mens Health. 2024 May 30. DOI: 10.5534/wjmh.240032. Online ahead of print. PMID: 38863376 FREE ARTICLE

Comments 1

Jens Rassweiler on Wednesday, 11 September 2024 11:00

The article investigates the effectiveness of radial low-intensity extracorporeal shockwave therapy (rESWT) in improving penile microvascular perfusion (PMP) in an aging rat model, with implications for treating erectile dysfunction (ED) in older men. ED is often linked to age-related declines in angiogenesis and smooth muscle function, contributing to vascular issues in penile tissue. This animal study aimed to evaluate rESWT's effects on PMP, explore its mechanisms, and assess changes in angiogenic markers and smooth muscle content.
For this purpose, Male rats (n=9; 15–18 months) were anesthetized and subjected to rESWT while monitoring PMP. The nitric oxide (NO) pathway involvement was assessed by measuring the effect of rESWT on PMP following an intracavernosal injection of N(G)-nitroarginine methyl ester (L-NAME) (NO synthase inhibitor). To elucidate the cellular mechanism, another group of rats received repeated rESWT (n=4) or no treatment (n=4) three times/week for two weeks. A Cenowave Air radial ESWT device was used for treatment (HNT MEDICAL Co.). Preliminary tests to compare the effect of probe size and intensity were conducted. A level 1 intensity (L1i) (0.12 mJ/mm2) ESWT session for 500 counts at 2 Hz with a 2 cm diameter probe was chosen as optimal settings to increase PMP for all treatment sessions in this study. ESWT sessions lasted ~4 minutes each. For PMP studies, a maximum of one session was performed within a two-week period to control for potential changes in long-term baseline PMP.
Key findings of this animal study include three main factors:
1. Increased PMP: rESWT significantly doubled PMP-levels compared to baseline, suggesting it effectively enhances blood flow in penile tissues using Laser speckle contrast imaging for microvascular perfusion.
2. NO Pathway Involvement: The use of an NO synthase inhibitor (L-NAME) reduced the rESWT-induced increase in PMP, indicating that the NO pathway plays a crucial role in the observed effects.
3. Angiogenic and Smooth Muscle Markers: Repeated rESWT elevated the expression of key markers like VEGF (vascular endothelial growth factor) and eNOS (endothelial nitric oxide synthase), as well as smooth muscle content, supporting improved vascular and smooth muscle health.
The study concludes that rESWT could be a promising non-invasive therapy for age-related ED, potentially offering similar benefits to focused ESWT but with greater convenience and accessibility due to its simpler device classification. Further research with larger samples is needed to fully understand the therapeutic mechanisms and benefits of rESWT.
Such studies are very important, since the final role of radial Shock Wave Therapy in the management of vasculogenic erectile dysfunction is still under debate. Evidently, the study of Ghahhari et al. 2022, also reviewed here, did not show any difference in a head-to-head comparison versus focused and linear Li-ESWT for erectile dysfunction., with all three showing significant therapeutic efficacy.

Jens Rassweiler

The article investigates the effectiveness of radial low-intensity extracorporeal shockwave therapy (rESWT) in improving penile microvascular perfusion (PMP) in an aging rat model, with implications for treating erectile dysfunction (ED) in older men. ED is often linked to age-related declines in angiogenesis and smooth muscle function, contributing to vascular issues in penile tissue. This animal study aimed to evaluate rESWT's effects on PMP, explore its mechanisms, and assess changes in angiogenic markers and smooth muscle content.
For this purpose, Male rats (n=9; 15–18 months) were anesthetized and subjected to rESWT while monitoring PMP. The nitric oxide (NO) pathway involvement was assessed by measuring the effect of rESWT on PMP following an intracavernosal injection of N(G)-nitroarginine methyl ester (L-NAME) (NO synthase inhibitor). To elucidate the cellular mechanism, another group of rats received repeated rESWT (n=4) or no treatment (n=4) three times/week for two weeks. A Cenowave Air radial ESWT device was used for treatment (HNT MEDICAL Co.). Preliminary tests to compare the effect of probe size and intensity were conducted. A level 1 intensity (L1i) (0.12 mJ/mm2) ESWT session for 500 counts at 2 Hz with a 2 cm diameter probe was chosen as optimal settings to increase PMP for all treatment sessions in this study. ESWT sessions lasted ~4 minutes each. For PMP studies, a maximum of one session was performed within a two-week period to control for potential changes in long-term baseline PMP. 
Key findings of this animal study include three main factors:
1.	Increased PMP: rESWT significantly doubled PMP-levels compared to baseline, suggesting it effectively enhances blood flow in penile tissues using Laser speckle contrast imaging for microvascular perfusion.
2.	NO Pathway Involvement: The use of an NO synthase inhibitor (L-NAME) reduced the rESWT-induced increase in PMP, indicating that the NO pathway plays a crucial role in the observed effects.
3.	Angiogenic and Smooth Muscle Markers: Repeated rESWT elevated the expression of key markers like VEGF (vascular endothelial growth factor) and eNOS (endothelial nitric oxide synthase), as well as smooth muscle content, supporting improved vascular and smooth muscle health.
The study concludes that rESWT could be a promising non-invasive therapy for age-related ED, potentially offering similar benefits to focused ESWT but with greater convenience and accessibility due to its simpler device classification. Further research with larger samples is needed to fully understand the therapeutic mechanisms and benefits of rESWT.
Such studies are very important, since the final role of radial Shock Wave Therapy in the management of vasculogenic erectile dysfunction is still under debate. Evidently, the study of Ghahhari et al. 2022, also reviewed here, did not show any difference in a head-to-head comparison versus focused and linear Li-ESWT for erectile dysfunction., with all three showing significant therapeutic efficacy.

Jens Rassweiler

The article investigates the effectiveness of radial low-intensity extracorporeal shockwave therapy (rESWT) in improving penile microvascular perfusion (PMP) in an aging rat model, with implications for treating erectile dysfunction (ED) in older men. ED is often linked to age-related declines in angiogenesis and smooth muscle function, contributing to vascular issues in penile tissue. This animal study aimed to evaluate rESWT's effects on PMP, explore its mechanisms, and assess changes in angiogenic markers and smooth muscle content. For this purpose, Male rats (n=9; 15–18 months) were anesthetized and subjected to rESWT while monitoring PMP. The nitric oxide (NO) pathway involvement was assessed by measuring the effect of rESWT on PMP following an intracavernosal injection of N(G)-nitroarginine methyl ester (L-NAME) (NO synthase inhibitor). To elucidate the cellular mechanism, another group of rats received repeated rESWT (n=4) or no treatment (n=4) three times/week for two weeks. A Cenowave Air radial ESWT device was used for treatment (HNT MEDICAL Co.). Preliminary tests to compare the effect of probe size and intensity were conducted. A level 1 intensity (L1i) (0.12 mJ/mm2) ESWT session for 500 counts at 2 Hz with a 2 cm diameter probe was chosen as optimal settings to increase PMP for all treatment sessions in this study. ESWT sessions lasted ~4 minutes each. For PMP studies, a maximum of one session was performed within a two-week period to control for potential changes in long-term baseline PMP. Key findings of this animal study include three main factors: 1. Increased PMP: rESWT significantly doubled PMP-levels compared to baseline, suggesting it effectively enhances blood flow in penile tissues using Laser speckle contrast imaging for microvascular perfusion. 2. NO Pathway Involvement: The use of an NO synthase inhibitor (L-NAME) reduced the rESWT-induced increase in PMP, indicating that the NO pathway plays a crucial role in the observed effects. 3. Angiogenic and Smooth Muscle Markers: Repeated rESWT elevated the expression of key markers like VEGF (vascular endothelial growth factor) and eNOS (endothelial nitric oxide synthase), as well as smooth muscle content, supporting improved vascular and smooth muscle health. The study concludes that rESWT could be a promising non-invasive therapy for age-related ED, potentially offering similar benefits to focused ESWT but with greater convenience and accessibility due to its simpler device classification. Further research with larger samples is needed to fully understand the therapeutic mechanisms and benefits of rESWT. Such studies are very important, since the final role of radial Shock Wave Therapy in the management of vasculogenic erectile dysfunction is still under debate. Evidently, the study of Ghahhari et al. 2022, also reviewed here, did not show any difference in a head-to-head comparison versus focused and linear Li-ESWT for erectile dysfunction., with all three showing significant therapeutic efficacy. Jens Rassweiler

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