Low-energy Shock Wave Research Articles

The Effectiveness of Radial Extracorporeal Shock Waves for Treatment of Carpal Tunnel Syndrome: A Randomized Clinical Trial

This study examined the effectiveness of radial extracorporeal shock wave therapy in the treatment of carpal tunnel syndrome (CTS). Forty patients with mild to moderate CTS were allocated to two groups: (i) shock wave + wrist splint and (ii) wrist splint. Patients used wrist splints followed by three sessions of low-energy shock wave therapy in the intervention group and wrist splints alone in the other group. The QuickDASH Questionnaire, visual analogue scale and nerve conduction studies were used to evaluate the patients before the study and at 3, 8 and 12 wk after the start of the treatment. At the end of the study, both groups saw the same clinical benefits. However, a significantly greater improvement in the median nerve distal sensory latency was noted in the shock wave group compared with the control group. We suggest that application of shock wave with alternative protocols may be effective in the treatment of CTS in future studies.

Defocused low-energy shock wave activates adipose tissue-derived stem cells in vitro via multiple signaling pathways

Background aimsWe found defocused low-energy shock wave (DLSW) could be applied in regenerative medicine by activating mesenchymal stromal cells. However, the possible signaling pathways that participated in this process remain unknown. In the present study, DLSW was applied in cultured rat adipose tissue-derived stem cells (ADSCs) to explore its effect on ADSCs and the activated signaling pathways. MethodsAfter treating with DLSW, the cellular morphology and cytoskeleton of ADSCs were observed. The secretions of ADSCs were detected. The expressions of ADSC surface antigens were analyzed using flow cytometry. The expressions of proliferating cell nuclear antigen and Ki67 were analyzed using western blot. The expression of CXCR2 and the migrations of ADSCs in vitro and in vivo were detected. The phosphorylation of selected signaling pathways with or without inhibitors was also detected. ResultsDLSW did not change the morphology and phenotype of ADSCs, and could promote the secretion, proliferation and migration of ADSCs. The phosphorylation levels were significantly higher in mitogen-activated protein kinases (MAPK) pathway, phosphoinositide 3-kinase (PI-3K)/AKT pathway and nuclear factor-kappa B (NF-κB) signaling pathway but not in Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Furthermore, ADSCs were not activated by DLSW after adding the inhibitors of these pathways simultaneously. ConclusionsOur results demonstrated for the first time that DLSW could activate ADSCs through MAPK, PI-3K/AKT and NF-κB signaling pathways. Combination of DLSW and agonists targeting these pathways might improve the efficacy of ADSCs in regenerative medicine in the future.

Low-energy extracorporeal shock wave therapy, preclinical and clinical studies

Floyd Dunn’s extensive research career contributed significantly to safety and efficacy of diagnostic and therapeutic ultrasound. Positive effects of low-energy shock wave therapy (SWT) show preclinical promise in renal disease in pigs and in cardiovascular disease in humans. Preclinical: a set of 26 pigs were divided into four groups, normal + SWT, atherosclerotic renal artery stenosis (ARAS) + SWT, and Normal and ARAS pigs. After three weeks of ARAS or sham, SWT was applied twice a week for three weeks. SWT after ARAS decreased blood pressure, recovered the stenotic microvascular density, improved renal blood flow and glomerular filtration rate, and decreased fibrosis. No noticeable kidney injury was observed. Low-energy SWT recovers the stenotic kidney toward normal function by preserving intra-renal microcirculation and may also alleviate renovascular hypertension. 72 patients with refractory angina, 43 were treated with low-energy SWT in the area peripheral to their infarct and 29 patients were in the control group. No adverse effects were seen in the treated group. At six months post-treatment angina class score was decreased (p = 0.0002), nitroglycerine use was reduced (p = 0.03), and hospitalization rate was reduced (p = 0.03). Low-energy shockwave therapy may be a tool for treating diseases caused by ischemia.

Immediate Dose–Response Effect of High-Energy Versus Low-Energy Extracorporeal Shock Wave Therapy on Cutaneous Microcirculation

Elucidation of the precise mechanisms and therapeutic options of extracorporeal shock wave therapy (ESWT) is only at the beginning. Although immediate real-time effects of ESWT on cutaneous hemodynamics have recently been described, the dose response to different ESWT energies in cutaneous microcirculation has never been examined. Thirty-nine Sprague–Dawley rats were randomly assigned to three groups that received either focused high-energy shock waves (group A: total of 1000 impulses, 10 J) to the lower leg of the hind limb, focused low-energy shock waves (group B: total of 300 impulses, 1 J) or placebo shock wave treatment (group C: 0 impulses, 0 J) using a multimodality shock wave delivery system (Duolith SD-1 T-Top, Storz Medical, Tägerwilen, Switzerland). Immediate microcirculatory effects were assessed with the O2C (oxygen to see) system (LEA Medizintechnik, Giessen, Germany) before and for 20 min after application of ESWT. Cutaneous tissue oxygen saturation increased significantly higher after high-energy ESWT than after low-energy and placebo ESWT (A: 29.4% vs. B: 17.3% vs. C: 3.3%; p = 0.003). Capillary blood velocity was significantly higher after high-energy ESWT and lower after low-energy ESWT versus placebo ESWT (group A: 17.8% vs. group B: −22.1% vs. group C: −5.0%, p = 0.045). Post-capillary venous filling pressure was significantly enhanced in the high-energy ESWT group in contrast to the low-energy ESWT and placebo groups (group A: 25% vs. group B: 2% vs. group C: −4%, p = 0.001). Both high-energy and low-energy ESWT affect cutaneous hemodynamics in a standard rat model. High-energy ESWT significantly increases parameters of cutaneous microcirculation immediately after application, resulting in higher tissue oxygen saturation, venous filling pressure and blood velocity, which suggests higher tissue perfusion with enhanced oxygen saturation, in contrast to low-energy as well as placebo ESWT. Low-energy ESWT also increased tissue oxygen saturation, albeit to a lower extent, and decreases both blood velocity and venous filling pressure. Low-energy ESWT reduced tissue perfusion, but improved oxygen saturation immediately after the application.

Using 300 Pretreatment Shock Waves in a Voltage Ramping Protocol Can Significantly Reduce Tissue Injury During Extracorporeal Shock Wave Lithotripsy

Pretreating a pig kidney with 500 low-energy shock waves (SWs) before delivering a clinical dose of SWs (2000 SWs, 24 kV, 120 SWs/min) has been shown to significantly reduce the size of the hemorrhagic lesion produced in that treated kidney, compared with a protocol without pretreatment. However, since the time available for patient care is limited, we wanted to determine if fewer pretreatment SWs could be used in this protocol. As such, we tested if pretreating with 300 SWs can initiate the same reduction in renal lesion size as has been observed with 500 SWs. Fifteen female farm pigs were placed in an unmodified Dornier HM-3 lithotripter, where the left kidney of each animal was targeted for lithotripsy treatment. The kidneys received 300 SWs at 12 kV (120 SWs/min) followed immediately by 2000 SWs at 24 kV (120 SWs/min) focused on the lower pole. These kidneys were compared with kidneys given a clinical dose of SWs with 500 SW pretreatment, and without pretreatment. Renal function was measured both before and after SW exposure, and lesion size analysis was performed to assess the volume of hemorrhagic tissue injury (% functional renal volume, FRV) created by the 300 SW pretreatment regimen. Glomerular filtration rate fell significantly in the 300 SW pretreatment group by 1 hour after lithotripsy treatment. For most animals, low-energy pretreatment with 300 SWs significantly reduced the size of the hemorrhagic injury (to 0.8% ± 0.4%FRV) compared with the injury produced by a typical clinical dose of SWs. The results suggest that 300 pretreatment SWs in a voltage ramping treatment regimen can initiate a protective response in the majority of treated kidneys and significantly reduce tissue injury in our model of lithotripsy injury.

Molecular mechanisms of the angiogenic effects of low-energy shock wave therapy: roles of mechanotransduction.

We have previously demonstrated that low-energy extracorporeal cardiac shock wave (SW) therapy improves myocardial ischemia through enhanced myocardial angiogenesis in a porcine model of chronic myocardial ischemia and in patients with refractory angina pectoris. However, the detailed molecular mechanisms for the SW-induced angiogenesis remain unclear. In this study, we thus examined the effects of SW irradiation on intracellular signaling pathways in vitro. Cultured human umbilical vein endothelial cells (HUVECs) were treated with 800 shots of low-energy SW (1 Hz at an energy level of 0.03 mJ/mm(2)). The SW therapy significantly upregulated mRNA expression and protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). The SW therapy also enhanced phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2) and Akt. Furthermore, the SW therapy enhanced phosphorylation of caveolin-1 and the expression of HUTS-4 that represents β1-integrin activity. These results suggest that caveolin-1 and β1-integrin are involved in the SW-induced activation of angiogenic signaling pathways. To further examine the signaling pathways involved in the SW-induced angiogenesis, HUVECs were transfected with siRNA of either β1-integrin or caveolin-1. Knockdown of either caveolin-1 or β1-integrin suppressed the SW-induced phosphorylation of Erk1/2 and Akt and upregulation of VEGF and eNOS. Knockdown of either caveolin-1 or β1-integrin also suppressed SW-induced enhancement of HUVEC migration in scratch assay. These results suggest that activation of mechanosensors on cell membranes, such as caveolin-1 and β1-integrin, and subsequent phosphorylation of Erk and Akt may play pivotal roles in the SW-induced angiogenesis.

Low-Energy Shockwave Therapy Improves Ischemic Kidney Microcirculation.

Microvascular rarefaction distal to renal artery stenosis is linked to renal dysfunction and poor outcomes. Low-energy shockwave therapy stimulates angiogenesis, but the effect on the kidney microvasculature is unknown. We hypothesized that low-energy shockwave therapy would restore the microcirculation and alleviate renal dysfunction in renovascular disease. Normal pigs and pigs subjected to 3 weeks of renal artery stenosis were treated with six sessions of low-energy shockwave (biweekly for 3 consecutive weeks) or left untreated. We assessed BP, urinary protein, stenotic renal blood flow, GFR, microvascular structure, and oxygenation in vivo 4 weeks after completion of treatment, and then, we assessed expression of angiogenic factors and mechanotransducers (focal adhesion kinase and β1-integrin) ex vivo A 3-week low-energy shockwave regimen attenuated renovascular hypertension, normalized stenotic kidney microvascular density and oxygenation, stabilized function, and alleviated fibrosis in pigs subjected to renal artery stenosis. These effects associated with elevated renal expression of angiogenic factors and mechanotransducers, particularly in proximal tubular cells. In additional pigs with prolonged (6 weeks) renal artery stenosis, shockwave therapy also decreased BP and improved GFR, microvascular density, and oxygenation in the stenotic kidney. This shockwave regimen did not cause detectable kidney injury in normal pigs. In conclusion, low-energy shockwave therapy improves stenotic kidney function, likely in part by mechanotransduction-mediated expression of angiogenic factors in proximal tubular cells, and it may ameliorate renovascular hypertension. Low-energy shockwave therapy may serve as a novel noninvasive intervention in the management of renovascular disease.

The study of low-intensity extracorporeal shock wave on rabbit's penile tissue of damage

Objective Observe the low-energy extracorporeal shock wave (LESW) on rabbit penile tissue damage and repair, and to investigate the security of LESW therapy on the erectile dysfunction (ED). Methods Common adult male rabbits(n=35) were randomly divided into 6 groups (5 experimental group, 1 control group). Same dose of LESW (E=0.09 mJ/m2, 60 shocks/min, 500 shocks each time on each side) treat on corpus cavernosum. Animals' penile tissue are observed the existence of the corresponding damage. Corpus cavernosum were made hematoxylin and eosin (HE), Masson staining and electron microscope. Penile tissue homogenate superoxide dismutase (SOD) activity was evaluated by xanthine oxidase method, thiobartituric acid (TBA) method to detect the contents of malondialdehyde (MDA). Results During the treatment, all rabbits no macroscopic damage occurred. HE staining microscope showed no inflammatory cell infiltration, outside the capillaries no overflow of red dlood cells. All experimental group the corpus cavernosum capillaries expansion. No significant differences between the experimental group. There is no obvious hyperplasia of collagen fibers in Masson staining. Scanning election microscopy (SEM): in group D, smooth muscle cells swelling, between cells, collagen increased obviously, capillary stracture incomplete. Penile tissue homogenate MDA content, respectively (5.63±2.48), (5.46±0.99), (4.25±0.89), (7.63±1.10), (6.73±1.51), (4.24±0.54) U/mg prot; MDA content, respectively(310.12±18.95), (321.26±32.58), (336.17±39.65), (287.13±35.56), (309.56±19.50), (358.43±45.80) U/(mg prot) group D compared with group F, the difference was statistically significant (P 0.05). Conclusion LESW can promote the penile tissue vascular endothelium expansion. There is no obvious collagen fibers deposition. LESW for the treatment of penile tissue two weeks continuous organization has no obvious damage to the penis, interval of 3 days of continuous treatment of penile tissue damage cannot be completely repaired. Key words: Low-energy extracorporeal shock wave; Corpus cavernosum; Damage; Rabbit

This Month in Investigative Urology

No AccessJournal of UrologyThis Month in Investigative Urology1 Aug 2016This Month in Investigative Urology Karl-Erik Andersson Karl-Erik AnderssonKarl-Erik Andersson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.05.077AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "This Month in Investigative Urology." The Journal of Urology, 196(2), pp. 299–300 References 1 : Promising effects of a novel EP2 and EP3 receptor dual agonist, ONO-8055, on neurogenic underactive bladder in a rat lumbar canal stenosis model. J Urol2016; 196: 609. Abstract, Google Scholar 2 : Role of PAR2 in the development of lower urinary tract dysfunction. J Urol2016; 196: 588. Link, Google Scholar 3 : Urodynamic and immunohistochemical evaluation of intravesical botulinum toxin A delivery using low energy shock waves. J Urol2016; 196: 599. Abstract, Google Scholar © 2016 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 196Issue 2August 2016Page: 299-300 Advertisement Copyright & Permissions© 2016 by American Urological Association Education and Research, Inc.MetricsAuthor Information Karl-Erik Andersson More articles by this author Expand All Advertisement PDF downloadLoading ...

Extracorporeal shock wave therapy for digital ulcers associated with systemic sclerosis

Patients with systemic sclerosis (SSc) often have Raynaud's phenomenon and digital skin ulcers. These ulcers are painful, and can sometimes cause major functional limitation. Skin ulcers are not associated with autoimmune factors or abnormal coagulation; hence, conventional immunosuppressive therapies, vasodilators, and anticoagulants are often ineffective. Sometimes, patients are forced to continue expensive medication without appreciable change. Therefore, the loss in time and expense for both patients and society is not negligible, and appropriate management is needed. Low-energy extracorporeal shock wave therapy (ESWT) enhances vascular endothelial growth factor production by endothelial cells and angiogenesis in vivo. Clinical application of low-energy ESWT for severe ischemic heart disease or refractory skin ulcers has been effective in treating ischemic symptoms. This treatment does not require anesthesia or any invasive procedure, and can be repeated without harmful side effects. We conducted a pilot study involving a small group of subjects to collect basic data on the efficacy and safety of ESWT for digital ulcers associated with SSc and to compare the effect of ESWT with that of conventional therapies. The results of our study suggest that ESWT has the potential to be a novel and efficacious treatment for digital ulcers associated with SSc, and can be added to pharmacological therapy.

PS-08-014 Assessment of the treatment efficacy of the low-energy shock wave therapy in patients with vascular erectile dysfunction

PS-08-014 Assessment of the treatment efficacy of the low-energy shock wave therapy in patients with vascular erectile dysfunction

AB032. A systematic review (meta-analysis): low energy shock wave improves erectile function

BackgroundAs a novel therapeutic method for erectile dysfunction (ED), the Low Energy Shock Wave (LESW) has been applied in the clinical setting recently. We feel that a summary of the current literature and a systematic review to evaluate the therapeutic efficacy of LESW for ED would be helpful for physicians who are interested in using this modality to treat patients.MethodsA comprehensive search of the PubMed and EMBASE databases to November 2015 was performed. Studies reporting on patients with ED treated by LESW were included. The international index of erectile function (IIEF) score and Erection Hardness Score (EHS) were the most commonly used tools to evaluate the therapeutic efficacy of LESW.ResultsThere were 14 studies including 806 patients from 2005 to 2015. Seven of the 14 studies were randomized controlled trials (RCTs). In these studies, the setup parameters of LESW and the protocols of treatment were in variation. The meta-analysis revealed that LESW could improve IIEF score (MD =2.00; 95% CI, 0.99–3.00; P<0.0001) and EHS score (RD =0.16; 95% CI, 0.03–0.28; P=0.01) significantly. The therapeutic efficacy could last at least three months. The patients with mild-moderate ED or without comorbidities had better therapeutic efficacy after treatment than patients with more severe ED or comorbidities. The energy density of LESW treatment was closely related to its clinical outcome, especially on IIEF improvement. More frequent treatment or longer treatment course did not improve IIEF score.ConclusionsStudies of LESW for ED patients increased sharply in recent years. Most of these studies presented encouraging results, regardless of variation in LESW setup parameters or treatment protocols. These studies suggest that LESW could significantly improve the IIEF and EHS score of ED patients. The publication of robust evidence from additional randomized controlled trials and longer-term follow-up would provide us more confidence regarding utilization of LESW treatment for ED patients.

AB017. Basic research progress in microenergy medicine

In the last decade, the convergence of life sciences, physical sciences, and engineering has brought a host of opportunities and innovations for biomedical informatics and health care in microenergy medicine, and it is called the third revolution in the field of life science research. Low-energy shock wave therapy (LESWT), a form of physical therapy in energy medicine, was shown to markedly improve erectile function in patients with organic ED, as well as in diabetic rats. In addition, LESWT has been demonstrated to facilitate elongation of myelinated axons, with consequent neurologic functional recovery in a rat model. Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound that delivered at a much lower intensity than traditional ultrasound energy and output in the mode of pulse wave. LIPUS have been demonstrated to have a rage of biological effects on tissues, including promoting bone-fracture healing, accelerating soft-tissue regeneration, inhibiting inflammatory responses and so on. Recent studies showed that biological effects of LIPUS in healing morbid body tissues may be mainly associated with the upregulation of cell proliferation and promoting multilineage differentiation of mesenchyme stem/progenitor cell lines. Therapeutic magnetic field, a good paradigm of convergence medicine, has been demonstrated to have beneficial results in benign prostatic hyperplasia (BPH), human breast carcinoma, peripheral nerve regeneration, hand osteoarthritis, osteonecrosis, and nucleic acid delivery. Magnetic field has been proven to be a safe, non-invasive method for numerous cell and tissue modifications, especially in musculoskeletal system.

MP54-17 A PROSPECTIVE STUDY ON THE EFFECT OF SHOCKWAVE LITHOTRIPSY ON RENAL FIBROSIS

You have accessJournal of UrologyStone Disease: Shock Wave Lithotripsy1 Apr 2016MP54-17 A PROSPECTIVE STUDY ON THE EFFECT OF SHOCKWAVE LITHOTRIPSY ON RENAL FIBROSIS Chi-Fai Ng, Sylvia Luke, Chi-Hang Yee, Kim Lee, John Yuen, and Danny Gohel Chi-Fai NgChi-Fai Ng More articles by this author , Sylvia LukeSylvia Luke More articles by this author , Chi-Hang YeeChi-Hang Yee More articles by this author , Kim LeeKim Lee More articles by this author , John YuenJohn Yuen More articles by this author , and Danny GohelDanny Gohel More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.587AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There was limited information on the effect of shockwave lithotripsy (SWL) on renal fibrosis. Therefore, we investigate the effect of SWL on renal fibrosis, using urinary procollagen III aminoterminal propeptide (PIIINP) level as a surrogate marker for renal fibrotic process, in human subjects after one section of SWL. Moreover, the role of two renal protective protocols, low-energy shockwave pretreatment protocol and pause-protection protocol, on renal fibrotic process would also be assessed. METHODS 320 patients with a solitary radiopaque renal stone < 15mm, were recruited prospectively for this study. Patients were randomized to receive one of four shockwave (SW) protocols: (1) receiving 80% power (19.2 kV) from beginning until the end of treatment; (2) receiving the first 100 SWs at 40% power (9.6 kV), followed by SWs at 80% power until the end of treatment; (3) receiving 100 shocks at 40% power, followed by a 3-minute pause and then further SWs at 80% power until the end of treatment; and (4) receiving 100 shocks at 80% power, followed by a 3-minute pause and then further SWs at 80% power until the end of treatment. Spot urine samples were collected before and after treatment for two year, for marker measurement. RESULTS Baseline information and treatment parameters of the four groups were comparable. There was no difference between the baseline PIIINP levels among the four treatment groups. There was a significant rise in PIIINP level from 6-weeks until 18 months after SWL for the whole group, as well as individual groups (p<0.05). The level of PIIINP reached a peak at 1-year after SWL and then gradually came back to baseline level at 2-year after SWL. (Figure 1) CONCLUSIONS SWL resulted in a prolonged increase in renal fibrotic process, which was similar in patients treated with different protective treatment protocols. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e733 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Chi-Fai Ng More articles by this author Sylvia Luke More articles by this author Chi-Hang Yee More articles by this author Kim Lee More articles by this author John Yuen More articles by this author Danny Gohel More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

880 Combination therapy using human adipose-derived stem cells on the cavernous nerve and low-energy shockwaves on the corpus cavernosum in a rat model of postprostatectomy erectile dysfunction

880 Combination therapy using human adipose-derived stem cells on the cavernous nerve and low-energy shockwaves on the corpus cavernosum in a rat model of postprostatectomy erectile dysfunction

Low-energy Shock Wave Treatment Induces Angiogenesis in Ischemic Muscle by Stimulation of Toll-like Receptor 3 Signaling

Objectives: Low energy shock waves (SW) have been shown to induce angiogenesis in ischemic myocardium. The mechanism translating the physical stimulus to a biological signal is unknown. Toll-like receptor (TLR)-3 is activated by RNA binding. It plays a key role in inflammation and angiogenesis. We therefore hypothesized that SW cause cellular cavitation, thus liberating cytoplasmic mRNA that activates TLR-3 as does the specific agonist Poly I:C. Effects are suppressed in TLR-3 silenced cells and in TLR-3 knock out mice.

Low-energy Shock Wave Therapy Ameliorates Erectile Dysfunction in a Pelvic Neurovascular Injuries Rat Model.

Erectile dysfunction (ED) caused by pelvic injuries is a common complication of civil and battlefield trauma with multiple neurovascular factors involved, and no effective therapeutic approach is available. To test the effect and mechanisms of low-energy shock wave (LESW) therapy in a rat ED model induced by pelvic neurovascular injuries. Thirty-two male Sprague-Dawley rats injected with 5-ethynyl-2'-deoxyuridine (EdU) at newborn were divided into 4 groups: sham surgery (Sham), pelvic neurovascular injury by bilateral cavernous nerve injury and internal pudendal bundle injury (PVNI), PVNI treated with LESW at low energy (Low), and PVNI treated with LESW at high energy (High). After LESW treatment, rats underwent erectile function measurement and the tissues were harvested for histologic and molecular study. To examine the effect of LESW on Schwann cells, in vitro studies were conducted. The intracavernous pressure (ICP) measurement, histological examination, and Western blot (WB) were conducted. Cell cycle, Schwann cell activation-related markers were examined in in vitro experiments. LESW treatment improves erectile function in a rat model of pelvic neurovascular injury by leading to angiogenesis, tissue restoration, and nerve generation with more endogenous EdU(+) progenitor cells recruited to the damaged area and activation of Schwann cells. LESW facilitates more complete re-innervation of penile tissue with regeneration of neuronal nitric oxide synthase (nNOS)-positive nerves from the MPG to the penis. In vitro experiments demonstrated that LESW has a direct effect on Schwann cell proliferation. Schwann cell activation-related markers including p-Erk1/2 and p75 were upregulated after LESW treatment. LESW-induced endogenous progenitor cell recruitment and Schwann cell activation coincides with angiogenesis, tissue, and nerve generation in a rat model of pelvic neurovascular injuries.

Shock Wave Enhances Angiogenesis through VEGFR2 Activation and Recycling.

Although low-energy shock wave (SW) is adopted to treat ischemic diseases because of its pro-angiogenic properties, the underlying mechanism remains unclear. This study aimed at testing whether SW-induced angiogenesis may be through endothelial vascular endothelial growth factor receptor 2 (VEGFR2) signaling and trafficking. Phosphorylation of VEGFR2-Akt-eNOS axis and production of nitric oxide (NO) were determined in human umbilical vein endothelial cells (HUVECs) treated with SW. Carotid artery in ob/ob mice was treated with SW before evaluation with sprouting assay. Critical limb ischemia was induced in ob/ob mice to evaluate blood flow recovery after SW treatment. Tube formation and migration assays were also performed with/without SW treatment in the presence/absence of SU5416 (VEGFR2 kinase inhibitor) and siRNA-driven silencing of VEGFR2. Chloroquine was used for disrupting endosome, and Rab11a controlling slow endocytic recycling was silenced with siRNA in vitro. Following SW treatment, augmented ligand-independent phosphorylation in VEGFR2-Akt-eNOS axis and endogenous NO production, increased cellular migration and tube formation, elevated sprouting of carotid artery and blood flow in ischemic limb in ob/ob mice were noted. Moreover, SU5416 and VEGFR2 silencing both inhibited SW-induced angiogenesis. SW-induced angiogenesis, which was accompanied by increased VEGFR2 protein expression without transcriptional change, was suppressed by chloroquine and Rab11a silencing. We concluded that SW enhanced angiogenesis via ligand-independent activation of VEGFR2 and further prolonged through endosome-to-plasma membrane recycling in endothelial cells.

Urodynamic and Immunohistochemical Evaluation of Intravesical Botulinum Toxin A Delivery Using Low Energy Shock Waves

We investigated the feasibility of using low energy shock waves for intravesical botulinum toxin A delivery. We also evaluated its efficacy for acetic acid induced bladder hyperactivity in rats. In study 1 magnetic resonance imaging with intravesical administration of Gd-DTPA (Gd-diethylenetriamine pentaacetic acid) contrast medium was performed to visualize increased bladder urothelial permeability after low energy shock waves. In study 2 saline (1 ml) or botulinum toxin A (20 U/1 ml saline) was administered in the bladder with or without lowenergy shock waves (300 pulses at 0.12 mJ/mm(2)) and retained for 1 hour on day 1. Continuous cystometrograms were performed on day 8 by filling the bladder with saline followed by 0.3% acetic acid. The bladder was harvested for histology, and SNAP-25, SNAP-23 and COX-2 expression by Western blot or immunostaining. Magnetic resonance imaging established bladder urothelial leakage of Gd-DTPA after low energy shock waves, which was not seen in controls. The intercontraction interval was decreased 71.9%, 72.6% and 70.6% after intravesical instillation of acetic acid in saline, saline plus low energy shock wave and botulinum toxin A pretreated rats, respectively. However, rats that received botulinum toxin A plus low energy shock waves showed a significantly reduced response (48.6% decreased intercontraction interval) to acetic acid instillation without compromising voiding function. Rats pretreated with botulinum toxin Aplus low energy shock waves showed a decreased inflammatory reaction (p<0.05), and decreased expression of SNAP-23 (p <0.05), SNAP-25 (p = 0.061) and COX-2 (p <0.05) compared with the control group. Low energy shock waves increased urothelial permeability, facilitated intravesical botulinum toxin A delivery and blocked acetic acid induced hyperactive bladder. These results support low energy shock waves as a promising method to deliver botulinum toxin A without the need for injection.

Extracorporeal Low-Energy Shock Wave Therapy Exerts Beneficial Anti-inflammatory Effects in Acute Myocardial Infarction in Rats in Vivo

Extracorporeal Low-Energy Shock Wave Therapy Exerts Beneficial Anti-inflammatory Effects in Acute Myocardial Infarction in Rats in Vivo