Low-energy Extracorporeal Shock Wave Therapy Research Articles

Effectiveness of non-surgical interventions for rotator cuff calcific tendinopathy: A systematic review.

To evaluate the effectiveness of non-surgical interventions for rotator cuff calcific tendinopathy. Medline, EMBASE, CINAHL, Cochrane Register of Clinical Trials, PEDro and SPORTDiscus from inception to March 2018, and accompanying reference lists. Peer-reviewed randomized clinical trials of non-surgical interventions for adults with rotator cuff calcific tendinopathy were included. The same 2 reviewers independently evaluated eligibility, extracted data and evaluated risk of bias of the included randomized clinical trials. A system to resolve any disagreements was established a priori. Short-term, medium-term and long-term outcomes for pain, shoulder function and calcific morphology related to rotator cuff calcific tendinopathy were extracted. Due to diversity in outcome measures a meta-analyses was not conducted. Of the 2,085 articles identified, 18 met the inclusion criteria, all of which had high risk of bias. Five non-surgical interventions were identified (extracorporeal shockwave therapy, ultrasound-guided percutaneous intervention, pulsed ultrasound, acetic acid iontophoresis, and transcutaneous electrical nerve stimulation). There was moderate evidence for high-energy extracorporeal shockwave therapy over low-energy extracorporeal shockwave therapy for pain and function between 3 and 6 months, and over placebo for function in the first 6 months. There was moderate evidence for ultrasound-guided percutaneous intervention over medium/high-energy extracorporeal shockwave therapy for reduced pain and calcific morphology over a 1-year period. Methodological concerns preclude definitive recommendations.

Improved renal outcomes after revascularization of the stenotic renal artery in pigs by prior treatment with low-energy extracorporeal shockwave therapy.

Revascularization does not restore renal function in most patients with atherosclerotic renal artery stenosis (RAS), likely because of inflammation and fibrosis within the stenotic kidney. Low-energy shockwave therapy (LE-SWT) stimulates angiogenesis in the stenotic kidney, but its ability to improve renal function and structure after revascularization remains unexplored. We tested the hypothesis that a LE-SWT regimen before percutaneous transluminal renal angioplasty (PTRA) would enable PTRA to restore renal function in hypercholesterolemic pigs with RAS (HC+RAS), and that this would be associated with attenuation of renal inflammation and fibrosis. Twenty-six pigs were studied after 16 weeks of HC+RAS, HC+RAS treated with PTRA with or without a preceding LE-SWT regimen (bi-weekly for 3 weeks), and controls. Single-kidney renal blood flow (RBF), glomerular filtration rate (GFR), and oxygenation were assessed in vivo using imaging 4 weeks after PTRA, and then inflammation and fibrosis ex vivo.Four weeks after successful PTRA, blood pressure fell similarly in both revascularized groups. Yet, stenotic-kidney GFR remained lower in HC+RAS and HC+RAS+PTRA (P < 0.01 vs. normal), but was improved in HC+RAS+PTRA+SW (P > 0.05 vs. normal). Furthermore, reduced inflammation, medullary fibrosis, and cortical hypoxia were only shown in swine stenotic kidneys pretreated with LE-SWT before PTRA 4 weeks later. LE-SWT delivery before revascularization permitted PTRA to improve function and decrease cortical and medullary damage in the stenotic swine kidney. This study, therefore, supports the use of an adjunct SW pretreatment to enhance the success of PTRA in blunting loss of kidney function in experimental HC+RAS.

Efficacy of Different Energy Levels Used in Focused and Radial Extracorporeal Shockwave Therapy in the Treatment of Plantar Fasciitis: A Meta-Analysis of Randomized Placebo-Controlled Trials.

The objective of this study was to assess the efficacy of different energy levels used in extracorporeal shockwave therapy (ESWT) in the treatment of plantar fasciitis using a systematic review and meta-analysis. We searched PubMed, Embase, and Cochrane library, from inception to March 2019 for randomized controlled trials that compared ESWT with placebo in patients with plantar fasciitis. The risk of bias for selected articles was assessed based on the Cochrane Handbook Systematic Review of Interventions. The pooled data were estimated by the mean difference or odds ratio. The meta-analysis showed that the high-energy ESWT group had a better success rate than the control group only at a three-month follow-up, but no significant difference between groups was observed for the other follow-up visits (1 and 12 months). In addition, no significant differences in visual analog scale (VAS) scores between groups were observed for all the follow-up visits (one-month and three-month). On the contrary, the medium-energy ESWT group had significantly better success rates than the control group for all the follow-up visits (3, 6, and 12 months). In addition, the medium-energy ESWT group had significant improvement in VAS scores compared with the control group for all the follow-up visits (1, 3, 6, and 12 months) after removing the extreme values. The low-energy ESWT group had significant improvement in VAS scores compared with the control group for all the follow-up visits (3 and 12 months). Otherwise, focused ESWT seems to be more effective than radial ESWT when compared with the control group. Use of local anesthesia can reduce the efficacy of low- and high-energy ESWTs. Our meta-analysis suggested that medium-energy ESWT in the treatment of plantar fasciitis was more effective than the control group. A limited number of trials related to low- and high-energy ESWTs were included in our meta-analysis. More research is required to confirm the efficacy of low- and high-energy ESWTs in future studies.

Low-Energy Extracorporeal Shock Wave Therapy Ameliorates Kidney Function in Diabetic Nephropathy.

Background Diabetic nephropathy is the most common cause of end-stage renal disease. Traditional therapy for diabetic nephropathy has focused on supportive treatment, and there is no significant effective therapy. We investigated the effect of low-energy extracorporeal shock wave therapy on a diabetic nephropathy rat model. Methods Streptozotocin-induced diabetic nephropathy rats were treated with six sessions of low-energy extracorporeal shock wave therapy (weekly for six consecutive weeks) or left untreated. We assessed urinary creatinine and albumin, glomerular volume, renal fibrosis, podocyte number, renal inflammation, oxidative stress, and tissue repair markers (SDF-1 and VEGF) six weeks after the completion of treatment. Results The six-week low-energy extracorporeal shock wave therapy regimen decreased urinary albumin excretion as well as reduced glomerular hypertrophy and renal fibrosis in the rat model of diabetic nephropathy. Moreover, low-energy extracorporeal shock wave therapy increased podocyte number in diabetic nephropathy rats. This was likely primarily attributed to the fact that low-energy extracorporeal shock wave therapy reduced renal inflammation and oxidative stress as well as increased tissue repair potency and cell proliferation. Conclusions Low-energy extracorporeal shock wave therapy preserved kidney function in diabetic nephropathy. Low-energy extracorporeal shock wave therapy may serve as a novel noninvasive and effective treatment of diabetic nephropathy.

Impacts of low-energy extracorporeal shockwave therapy on pain, pruritus, and health-related quality of life in patients with burn: A randomized placebo-controlled study

BackgroundThe management of post-burn pain and pruritus remain a potent challenge because of their bad effects on health-related quality of life (HRQOL). The main purpose of this study was to evaluate the impacts of low-energy extracorporeal shockwave therapy (low-energy ESWT) in the management of pain, pruritus, and HRQOL in patients with burn. MethodsForty-five adult patients with burn, their age ranged from 18 to 55 years, were included in the study, they randomly assigned into 22 patients in the study group (low-energy ESWT) and 23 patients in the placebo group. The study group received low-energy ESWT (0.05–0.20mJ/mm2, a frequency of 4Hz with total shocks from 1000 to 2000 shocks) once per week for 4 successive weeks, while the placebo group received ESWT without energy. Both groups received traditional physical therapy program of selective different exercises (respiratory, range of motion, endurance, strengthening, balance, mobilization, stretching, and gait training) 3days per week for 4 weeks. Numerical Rating Scale (NRS) for pain and for pruritus, Pressure Pain Threshold (PPT), 12-Item Pruritus Severity Scale (12-PSS), and Burn Specific Health Scale-Brief (BSHS-B) were measured before and after treatment procedures in both groups. ResultsNRS were decreased significantly in the study group than in the placebo group (P<0.05). PPT, 12-PSS, and BSHS-B scores were improved more significantly in the study group than in the placebo group (P<0.05) while body image and burn associated issues were improved at the same level in both groups (P>0.05). ConclusionThe findings suggest that low-energy ESWT with traditional regular physical therapy may relive post-burn pain and pruritus, and improve HRQOL, particularly in adult patients with burn.

Combined Adipose-Derived Mesenchymal Stem Cells and Low-Energy Extracorporeal Shock Wave Therapy Protect the Brain From Brain Death-Induced Injury in Rat.

This study tested the hypothesis that combined adipose-derived mesenchymal stem cell (ADMSC) and low-energy extracorporeal shock wave (ECSW) therapy could protect brain from brain death (BD)-induced injury. Adult male Sprague Dawley rats were categorized into group 1 (sham control), group 2 (BD), group 3 (BD + ECSW [0.15 mJ/mm2/300 impulses] applied to the skull surface 3 hours after BD induction), group 4 (BD + ADMSC [1.2 × 106 cell] by intravenous injection 3 hours after BD induction) and group 5 (BD + ECSW + ADMSC). By 6 hours after BD induction, circulating/spleen levels of immune cells (CD3/CD4+, CD8/CD4+, Treg+) and circulating levels of inflammatory cells (MPO/Ly6G/CD11a/b) and soluble mediators (TNF-α/IL-6) were lowest in group 1 and significantly progressively reduced from groups 2 to 5 (all p < 0.0001). Brain protein expressions of inflammatory (TNF-α/NF-κB/MMP-9/IL-1β), apoptotic (caspase-3/PARP/mitochondrial-BAX), oxidative stress/DNA-damage (NOX-1/NOX-2/oxidized protein/γ-H2AX) biomarkers exhibited an identical pattern, whereas anti-oxidant (SIRT1/SIRT3) and mitochondrial-integrity (mitochondrial-cytochrome-C) biomarkers exhibited an opposite pattern to inflammatory biomarkers among the 5 groups (all p < 0.0001). The cellular expressions of inflammatory/brain-edema (F4/80/CD14+/GFAP/AQP4) biomarkers exhibited an identical pattern to inflammation among the 5 groups (all p < 0.0001). In conclusion, ECSW-ADMSC therapy is superior to either alone for attenuating brain from BD-induced damage.

Long-term outcome of low-energy extracorporeal shockwave therapy on gluteal tendinopathy documented by magnetic resonance imaging.

BackgroundPrevious outcome studies for extracorporeal shock wave therapy (ESWT) have included clinically diagnosed greater trochanteric pain syndrome (GTPS). The purpose of this study is to investigate outcome of ESWT on GTPS with gluteal tendinopathy documented by magnetic resonance imaging (MRI).MethodsMedical records of 38 consecutive patients were retrospectively reviewed, who underwent ESWT for GTPS with MRI-documented gluteal tendinopathy (> 6 months). ESWT was conducted (1/week) when the Roles-Maudsley score (RMS) showed “Poor” or “Fair” grade after conservative treatment until RMS had reached “Good” or “Excellent” grade (treatment success) or until 12 treatments had been applied. Numeric rating scale (NRS) and RMS were evaluated before, 1 week after (immediate follow-up) and mean 27 months after ESWT program (long-term follow-up). Success rate was calculated at each follow-up point.ResultsInitial NRS (5.9 ± 1.6) significantly decreased at immediate (2.5 ± 1.5, p< 0.01) and long-term follow-up (3.3 ± 3.0, p< 0.01), respectively. Success rates were 83.3% (immediate) and 55.6% (long-term), respectively. There was no correlation among age, symptom duration and NRS.ConclusionLow-energy ESWT can be an effective treatment for pain relief in chronic GTPS with MRI-documented gluteal tendinopathy. However, its long-term effect appears to decrease with time.

High- versus low-energy extracorporeal shock-wave therapy for myofascial pain syndrome of upper trapezius: A prospective randomized single blinded pilot study.

Background:To compare the efficacy of high- and low-energy extracorporeal shock wave therapy (ESWT) for patients with myofascial pain syndrome (MPS) of the upper trapezius.Methods:Thirty patients (3 men, 27 women) were randomly assigned to receive either high-energy ESWT (0.210 mJ/mm2) or low-energy ESWT (0.068 mJ/mm2). Both groups received 1500 pulses of ESWT once a week, for 2 weeks. Outcome measurement was assessed by verbal numeric pain scale (VNS), neck disability index (NDI), neck range of motion (ROM) (flexion, extension, rotation, lateral bending), and pressure threshold (PT). Statistical analysis was performed with significance level of P < .05.Results:No statistically significant differences of demographic and clinical characteristics existed between the 2 groups. VNS, NDI, neck ROM (rotation to sound side, lateral bending to affected side, lateral bending to sound side), and PT were improved in both groups. In contrast, statistically significant improvements in neck flexion and neck extension were observed only in the high-energy group. We also found significant differences in post-treatment NDI (4.20 ± 1.78 vs 6.47 ± 2.48) and post-treatment neck flexion ROM (65.47 ± 10.09 vs 55.93 ± 11.07) between high-energy and low-energy group.Conclusion:ESWT effectively improves VNS, NDI, neck ROM, and PT to patients with MPS of the upper trapezius. High-energy ESWT was more effective in improving NDI and neck flexion ROM compared to the low-energy ESWT, suggesting superiority in functional improvement. Further studies are required to specify the effect of ESWT by energy intensity.

Low-energy extracorporeal shockwave therapy (ESWT) improves metaphyseal fracture healing in an osteoporotic rat model.

PurposeAs result of the current demographic changes, osteoporosis and osteoporotic fractures are becoming an increasing social and economic burden. In this experimental study, extracorporeal shock wave therapy (ESWT), was evaluated as a treatment option for the improvement of osteoporotic fracture healing.MethodsA well-established fracture model in the metaphyseal tibia in the osteoporotic rat was used. 132 animals were divided into 11 groups, with 12 animals each, consisting of one sham-operated group and 10 ovariectomized (osteoporotic) groups, of which 9 received ESWT treatment. Different energy flux intensities (0.15 mJ/mm2, 0.35 mJ/mm2, or 0.55 mJ/mm2) as well as different numbers of ESWT applications (once, three times, or five times throughout the 35-day healing period) were applied to the osteoporotic fractures. Fracture healing was investigated quantitatively and qualitatively using micro-CT imaging, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, histomorphometric analysis and biomechanical analysis.ResultsThe results of this study show a qualitative and quantitative improvement in the osteoporotic fracture healing under low-energy (energy flux intensity: 0,15 mJ/mm2) ESWT and with fewer treatment applications per healing period.ConclusionIn conclusion, low-energy ESWT seems to exhibit a beneficial effect on the healing of osteoporotic fractures, leading to improved biomechanical properties, enhanced callus-quantity and -quality, and an increase in the expression of bone specific transcription factors. The results suggest that low-energy ESWT, as main treatment or as adjunctive treatment in addition to a surgical intervention, may prove to be an effective, simple to use, and cost-efficient option for the qualitative and quantitative improvement of osteoporotic fracture healing.

Low-intensity Extracorporeal Shock Wave Therapy for Erectile Dysfunction: A Systematic Review and Meta-analysis

To assess the efficacy of low-energy extracorporeal shock wave therapy (LI-ESWT) for erectile dysfunction (ED), a systematic review and meta-analysis was undertaken. A comprehensive search of the PubMed, Cochrane Register, and Embase databases to March 2017 was performed for randomized controlled trials reporting on patients with ED treated with LI-ESWT. The International Index of Erectile Function (IIEF) and the Erection Hardness Score (EHS) were the most commonly used tools to evaluate the therapeutic efficacy of LI-ESWT. There were 9 studies including 637 patients from 2005 to 2017. The meta-analysis revealed that LI-ESWT could significantly improve IIEF (mean difference [MD]: 2.54; 95% confidence interval [CI], 0.83-4.25; P = .004) and EHS (risk difference [RD]: 0.16; 95% CI, 0.03-0.28; P = .01). Therapeutic efficacy could last at least 3 months (MD: 4.15; 95% CI, 1.40-6.90; P = .003). Lower energy density (0.09 mJ/mm2, MD: 4.14; 95% CI, 0.87-7.42; P = .01) increased the number of pulses (3000 pulses per treatment, MD: 5.11; 95% CI, 3.18-7.05, P < .0001) and shorter total treatment courses (<6 weeks, MD: 3.73; 95% CI, 0.54-6.93; P = .02) resulted in better therapeutic efficacy. These studies suggest that LI-ESWT could significantly improve the IIEF and EHS of patients with ED. The publication of robust evidence from additional randomized controlled trials and longer-term follow-up would provide more confidence regarding the use of LI-ESWT for patients with ED.

AB024. Safety evaluation of low-energy extracorporeal shock wave therapy to rat testes

BackgroundThe purpose of the study is to determine the optimal energy frequency of LESWT to rat testes by comparing three different shock wave frequencies.MethodsA total of 40 healthy Sprague-Dawley (SD) rats were randomly assigned to a blank group (C group) in which 5 rats received no treatment, a sham group (B group) in which 5 rats only exposed to shockwave, and LESWT groups (A group) in which 30 rats separately exposed to 0.02 mJ/mm2 (A1 group), 0.04 mJ/mm2 (A2 group), and 0.06 mJ/mm2 (A3 group). The changes of rat weight among these five groups were compared. Eenzyme-linked immunosorbent assay (ELISA) was performed to measure the concentrations of testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Testicular mass index (TMI) of rat bilateral testes was compared. A transmission electron microscopy (TEM) was used to observe the microstructure of testes in rats among five groups.ResultsAfter a 2-week period of low-energy extracorporeal shock wave therapy (LESWT), the rat weight changed significantly between A1 and A3 groups but did not differ among A1, A2, B, and C groups (P=0.09, 0.31, 0.47); no significant difference in T, LH, and FSH concentrations was observed when the A1 group was respectively compared with other four groups (P=0.11, 0.33, 0.19, 0.47); the TMI of rat testes in the A1 group was significantly different from that in the A3 group (P=0.04). Observations from the TEM showed that rats exhibited normal microstructure of testes in A1, B, and C groups. Mitochondrial swelling, dissolution of cristae, and dilated intercellular space occurred in the A2 group. Mitochondrial vacuolization, nuclear perturbations, cytoplasmic segregation, and necrotic cells were observed in the A3 group.ConclusionsTaken together, we conclude that 0.02 mJ/mm2 LESWT exerts no significant influence on rat weight, T, LH, FSH, TMI of testes, and microstructure, which may be regarded as the safe frequency for rat testes undergoing LESWT. Furthermore, our study demonstrates that TEM is one of the most reliable methods for evaluating the effect of LESWT on microstructures of rat testes.

Improvement of adipose tissue–derived cells by low-energy extracorporeal shock wave therapy

BackgroundCell-based therapies with autologous adipose tissue–derived cells have shown great potential in several clinical studies in the last decades. The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue–derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. MethodsIn our experimental set-up, low-energy extracorporeal shock wave therapy (ESWT) was performed on freshly obtained human adipose tissue and isolated adipose tissue SVF cells aiming to equalize and enhance stem cell properties and functionality. ResultsAfter ESWT on adipose tissue we could achieve higher cellular adenosine triphosphate (ATP) levels compared with ESWT on the isolated SVF as well as the control. ESWT on adipose tissue resulted in a significantly higher expression of single mesenchymal and vascular marker compared with untreated control. Analysis of SVF protein secretome revealed a significant enhancement in insulin-like growth factor (IGF)-1 and placental growth factor (PLGF) after ESWT on adipose tissue. DiscussionSummarizing we could show that ESWT on adipose tissue enhanced the cellular ATP content and modified the expression of single mesenchymal and vascular marker, and thus potentially provides a more regenerative cell population. Because the effectiveness of autologous cell therapy is dependent on the therapeutic potency of the patient's cells, this technology might raise the number of patients eligible for autologous cell transplantation.

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

PurposeGene 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 MethodsDiabetes 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.ResultsIn 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).ConclusionsElectromagnetic 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.

Low-energy versus middle-energy extracorporeal shockwave therapy for the treatment of snapping scapula bursitis.

Objective:Extracorporeal shockwave therapy (ESWT) has been used successfully in treatment of musculoskeletal disorders. Our objective was to assess the effectiveness of low versus middle-energy ESWT on snapping scapula bursitis.Methods:Thirty-five patients, divided into two groups, group (L), received low-energy ESWT, group (M) received middle-energy ESWT. Groups were evaluated at 1,3,6 and 12 months using the Visual Analogue Scale (VAS), the Constant-Murley scoring (CMS) and the Roles and Maudsley criteria.Results:In groups (L) and (M), VAS average values after 1,3,6 months and one year were (43±5.17, 38±4.33, 28±4.18 and 19±3.39) and (37±4.85, 26±4.74, 21±4.45 and 7±3.42) respectively. At six and twelve months, statistical difference was detected, P (0.034, 0.026) respectively. After one year of completing the treatment, the average values of CMS were (83.5±6.44 and 91±5.33) respectively, P=0.046. Roles and Maudsley criteria demonstrated that, patients in group (L), 6 (35%) excellent, 5 (29%) good, 4 (24%) acceptable and 2 (12%) had poor results. Whereas, patients in group (M), 11 (61%) excellent, 3 (17%) good, 3 (17%) acceptable and 1 (5%) had poor results.Conclusion:Although low-energy ESWT showed good early-term results, but middle-energy ESWT protocol demonstrated better early-term, Mid-term, and late-term results.

Effect of Low-Energy Linear Shockwave Therapy on Erectile Dysfunction—A Double-Blinded, Sham-Controlled, Randomized Clinical Trial

IntroductionPrevious studies have shown that focal low-energy extracorporeal shockwave therapy (Li-ESWT) can have a positive effect in men with erectile dysfunction (ED). Linear Li-ESWT (LLi-ESWT) for ED has not been previously assessed in a randomized trial. AimTo evaluate the treatment outcome of LLi-ESWT for ED. MethodsMen with ED (n = 126) and a score lower than 25 points on the International Index of Erectile Function erectile function domain (IIEF-EF) were included. Subjects were allocated to receive LLi-ESWT once a week for 5 weeks or sham treatment once a week for 5 weeks. After a 4-week break, the two groups received active treatment once a week for 5 weeks. Subjects completed the IIEF, Erection Hardness Scale (EHS), Sexual Quality of Life–Men, and the Erectile Dysfunction Inventory of Treatment Satisfaction at baseline, after 9 weeks, and after 18 weeks. Main Outcome MeasuresThe primary outcome measurement was an increase of at least five points on the IIEF-EF score. The secondary outcome measurement was an increased EHS score to at least 3 in men with a score no higher than 2 at baseline. Data were analyzed by linear and logistic regression. ResultsMean IIEF-EF scores were 11.5 at baseline (95% CI = 9.8–13.2), 13.0 after five sessions (95% CI = 11.0–15.0), and 12.6 after 10 sessions (95% CI = 11.0–14.2) in the sham group and correspondingly 10.9 (95% CI = 9.1–12.7), 13.1 (95% CI = 9.3–13.4), and 11.8 (95% CI = 10.1–13.4) in the ESWT group. Success rates based on IIEF-EF score were 38.3% in the sham group and 37.9% in the ESWT group (odds ratio = 0.95, 95% CI = 0.45–2.02, P = .902). Success rates based on EHS score were 6.7% in the sham group and 3.5% in the ESWT group (odds ratio = 0.44, 95% CI = 0.08–2.61, P = .369). A limitation of this study is that device settings (number of shockwaves and penetration depth) were estimated based on an existing trial on focused ESWT. ConclusionNo clinically relevant effect of LLi-ESWT on ED was found.

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.

Effect of low-energy extracorporeal shock wave on vascular regeneration after spinal cord injury and the recovery of motor function.

BackgroundLatest studies show that low-energy extracorporeal shock wave therapy (ESWT) can upregulate levels of vascular endothelial growth factor (VEGF). VEGF can ease nervous tissue harm after spinal cord injury (SCI). This study aims to explore whether low-energy ESWT can promote expression of VEGF, protect nervous tissue after SCI, and improve motor function.MethodsNinety adult female rats were divided into the following groups: Group A (simple laminectomy), Group B (laminectomy and low-energy ESWT), Group C (spinal cord injury), and Group D (spinal cord injury and low-energy ESWT). Impinger was used to cause thoracic spinal cord injury. Low-energy ESWT was applied as treatment after injury three times a week, for 3 weeks. After SCI, the Basso, Beattie, and Bresnahan (BBB) scale was used to evaluate motor function over a period of 42 days at different time points. Hematoxylin and eosin (HE) staining was used to evaluate nerve tissue injury. Neuronal nuclear antigen (NeuN) staining was also used to evaluate loss of neurons. Polymerase chain reaction was used to detect messenger RNA (mRNA) expression of VEGF and its receptor fms-like tyrosine kinase 1 (Flt-1). Immunostaining was used to evaluate VEGF protein expression level in myeloid tissue.ResultsBBB scores of Groups A and B showed no significant result related to dyskinesia. HE and NeuN staining indicated that only using low-energy ESWT could not cause damage of nervous tissue in Group B. Recovery of motor function at 7, 35, and 42 days after SCI in Group D was better than that in Group C (P<0.05). Compared with Group C, number of NeuN-positive cells at 42 days after SCI increased significantly (P<0.05). The mRNA levels of VEGF and Flt-1 and VEGF expression at 7 days after SCI in Group D were significantly higher than those in Group C (P<0.05).ConclusionLow-energy ESWT promotes expression of VEGF, decreases secondary damage of nerve tissue, and improves recovery of motor function. It can be regarded as one mode of clinical routine adjunctive therapy for spinal 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 extracorporeal shock wave therapy for promotion of vascular endothelial growth factor expression and angiogenesis and improvement of locomotor and sensory functions after spinal cord injury.

OBJECTIVE Extracorporeal shock wave therapy (ESWT) is widely used to treat various human diseases. Low-energy ESWT increases expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. The VEGF stimulates not only endothelial cells to promote angiogenesis but also neural cells to induce neuroprotective effects. A previous study by these authors demonstrated that low-energy ESWT promoted expression of VEGF in damaged neural tissue and improved locomotor function after spinal cord injury (SCI). However, the neuroprotective mechanisms in the injured spinal cord produced by low-energy ESWT are still unknown. In the present study, the authors investigated the cell specificity of VEGF expression in injured spinal cords and angiogenesis induced by low-energy ESWT. They also examined the neuroprotective effects of low-energy ESWT on cell death, axonal damage, and white matter sparing as well as the therapeutic effect for improvement of sensory function following SCI. METHODS Adult female Sprague-Dawley rats were divided into the SCI group (SCI only) and SCI-SW group (low-energy ESWT applied after SCI). Thoracic SCI was produced using a New York University Impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks after SCI. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan open-field locomotor score for 42 days after SCI. Mechanical and thermal allodynia in the hindpaw were evaluated for 42 days. Double staining for VEGF and various cell-type markers (NeuN, GFAP, and Olig2) was performed at Day 7; TUNEL staining was also performed at Day 7. Immunohistochemical staining for CD31, α-SMA, and 5-HT was performed on spinal cord sections taken 42 days after SCI. Luxol fast blue staining was performed at Day 42. RESULTS Low-energy ESWT significantly improved not only locomotion but also mechanical and thermal allodynia following SCI. In the double staining, expression of VEGF was observed in NeuN-, GFAP-, and Olig2-labeled cells. Low-energy ESWT significantly promoted CD31 and α-SMA expressions in the injured spinal cords. In addition, low-energy ESWT significantly reduced the TUNEL-positive cells in the injured spinal cords. Furthermore, the immunodensity of 5-HT-positive axons was significantly higher in the animals treated by low-energy ESWT. The areas of spared white matter were obviously larger in the SCI-SW group than in the SCI group, as indicated by Luxol fast blue staining. CONCLUSIONS The results of this study suggested that low-energy ESWT promotes VEGF expression in various neural cells and enhances angiogenesis in damaged neural tissue after SCI. Furthermore, the neuroprotective effect of VEGF induced by low-energy ESWT can suppress cell death and axonal damage and consequently improve locomotor and sensory functions after SCI. Thus, low-energy ESWT can be a novel therapeutic strategy for treatment of SCI.