The dynamic response of human lungs due to underwater shock wave exposure.

Since the 19th century, underwater explosions have posed a significant threat to service members. While there have been attempts to establish injury criteria for the most vulnerable organs, namely the lungs, existing criteria are highly variable due to insufficient human data and the corresponding inability to understand the underlying injury mechanisms. This study presents an experimental characterization of isolated human lung dynamics during simulated exposure to underwater shock waves. We found that the large acoustic impedance at the surface of the lung severely attenuated transmission of the shock wave into the lungs. However, the shock wave initiated large bulk pressure-volume cycles that are distinct from the response of the solid organs under similar loading. These pressure-volume cycles are due to compression of the contained gas, which we modeled with the Rayleigh-Plesset equation. The extent of these lung dynamics was dependent on physical confinement, which in real underwater blast conditions is influenced by factors such as rib cage properties and donned equipment. Findings demonstrate a potential causal mechanism for implosion injuries, which has significant implications for the understanding of primary blast lung injury due to underwater blast exposures.

Efficacy and safety of cardiac shock wave therapy for patients with severe coronary artery disease: A randomized, double-blind control study.

BACKGROUND: Previous studies proved the efficacy of cardiac shock wave therapy (CSWT) for coronary artery disease (CAD) patients who are not candidate for reperfusion therapy. Randomized control trials are limited. We try to explore the efficacy and safety of CSWT for patients with severe CAD. METHODS: Thirty patients with severe CAD who had obvious ischemia on myocardial perfusion imaging (MPI) were enrolled and randomly assigned to the CSWT group or the control group. They had received optimal medication treatment for at least three months. Nine sessions of shock wave therapy were conducted over 3 months. CSWT group received the real treatment, while the control group received the pseudo-treatment. Clinical symptom, imaging outcomes and safety parameters were compared between two groups. RESULTS: After treatment, regional stress score (P = .023), improvement rate (IR) of ischemic area (IA) stress (P < .001) and IR of IA difference (P < .001) were significantly favor CSWT group. The interaction of summed rest score (P < .001), summed stress score (P = .004), summed difference score (P = .036) were significantly improved in the CSWT group compared to the control group. Seattle angina questionnaire, quality of life (QOL) and the distance of six-minute walking test (6MWT) were improved in both groups without significant difference between them. Hemodynamic parameters were stable during procedure. Myocardial injury markers showed no changes in two groups. CONCLUSIONS: Our study demonstrated CSWT could effectively and safely improve myocardial perfusion in patients with severe CAD. Clinical symptom, QOL and 6MWT were all improved after treatment, but no significant difference between two groups.

Effect of shock wave power spectrum on the inner ear pathophysiology in blast-induced hearing loss.

Blast exposure can induce various types of hearing impairment, including permanent hearing loss, tinnitus, and hyperacusis. Herein, we conducted a detailed investigation of the cochlear pathophysiology in blast-induced hearing loss in mice using two blasts with different characteristics: a low-frequency dominant blast generated by a shock tube and a high-frequency dominant shock wave generated by laser irradiation (laser-induced shock wave). The pattern of sensorineural hearing loss (SNHL) was low-frequency- and high-frequency-dominant in response to the low- and high-frequency blasts, respectively. Pathological examination revealed that cochlear synaptopathy was the most frequent cochlear pathology after blast exposure, which involved synapse loss in the inner hair cells without hair cell loss, depending on the power spectrum of the blast. This pathological change completely reflected the physiological analysis of wave I amplitude using auditory brainstem responses. Stereociliary bundle disruption in the outer hair cells was also dependent on the blast's power spectrum. Therefore, we demonstrated that the dominant frequency of the blast power spectrum was the principal factor determining the region of cochlear damage. We believe that the presenting models would be valuable both in blast research and the investigation of various types of hearing loss whose pathogenesis involves cochlear synaptopathy.

The utilization of small non-mammals in traumatic brain injury research: A systematic review.

Traumatic brain injury (TBI) is the leading cause of death and disability worldwide and has complicated underlying pathophysiology. Numerous TBI animal models have been developed over the past decade to effectively mimic the human TBI pathophysiology. These models are of mostly mammalian origin including rodents and non-human primates. However, the mammalian models demanded higher costs and have lower throughput often limiting the progress in TBI research. Thus, this systematic review aims to discuss the potential benefits of non-mammalian TBI models in terms of their face validity in resembling human TBI. Three databases were searched as follows: PubMed, Scopus, and Embase, for original articles relating to non-mammalian TBI models, published between January 2010 and December 2019. A total of 29 articles were selected based on PRISMA model for critical appraisal. Zebrafish, both larvae and adult, was found to be the most utilized non-mammalian TBI model in the current literature, followed by the fruit fly and roundworm. In conclusion, non-mammalian TBI models have advantages over mammalian models especially for rapid, cost-effective, and reproducible screening of effective treatment strategies and provide an opportunity to expedite the advancement of TBI research.

Global gene expression profiling of blast lung injury of goats exposed to shock wave.

PURPOSE: Blast lung injury (BLI) is the most common damage resulted from explosion-derived shock wave in military, terrorism and industrial accidents. However, the molecular mechanisms underlying BLI induced by shock wave are still unclear. METHODS: In this study, a goat BLI model was established by a fuel air explosive power. The key genes involved in were identified. The goats of the experimental group were fixed on the edge of the explosion cloud, while the goats of the control group were 3 km far away from the explosive environment. After successful modeling for 24 h, all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to identify the main enriched biological functions of differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency of gene expression. RESULTS: Of the sampled goat lungs, 895 genes were identified to be significantly differentially expressed, and they were involved in 52 significantly enriched GO categories. KEGG analysis revealed that DEGs were highly enriched in 26 pathways, such as cytokine-cytokine receptor interaction, antifolate resistance, arachidonic acid metabolism, amoebiasis and bile secretion, JAK-STAT, and IL-17 signaling pathway. Furthermore, 15 key DEGs involved in the biological processes of BLI were confirmed by qRT-PCR, and the results were consistent with RNA sequencing. CONCLUSION: Gene expression profiling provide a better understanding of the molecular mechanisms of BLI, which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.

A numerical simulation method of natural fragment formation and injury to human thorax.

OBJECTIVE: Fragment injury is a type of blast injury that is becoming more and more common in military campaigns and terrorist attacks. Numerical simulation methods investigating the formation of natural fragments and injuries to biological targets are expected to be developed. METHODS: A cylindrical warhead model was established and the formation process of natural fragments was simulated using the approach of tied nodes with failure through the explicit finite element (FE) software of LS-DYNA. The interaction between the detonation product and the warhead shell was simulated using the fluid-structure interaction algorithm. A method to simulate the injury of natural fragments to a biological target was presented by transforming Lagrange elements into smooth particle hydrodynamics (SPH) particles after the natural fragments were successfully formed. A computational model of the human thorax was established to simulate the injury induced by natural fragments by the node-to-surface contact algorithm with erosion. RESULTS: The discontinuous velocities of the warhead shell at different locations resulted in the formation of natural fragments with different sizes. The velocities of natural fragments increased rapidly at the initial stage and slowly after the warhead shell fractured. The initial velocities of natural fragments at the central part of the warhead shell were the largest, whereas those at both ends of the warhead shell were the smallest. The natural fragments resulted in bullet holes that were of the same shape as that of the fragments but slightly larger in size than the fragments in the human thorax after they penetrated through. Stress waves propagated in the ribs and enhanced the injury to soft tissues; additionally, ballistic pressure waves ahead of the natural fragments were also an injury factor to the soft tissues. CONCLUSION: The proposed method is effective in simulating the formation of natural fragments and their injury to biological targets. Moreover, this method will be beneficial for simulating the combined injuries of natural fragments and shock waves to biological targets.

Safety and efficacy of direct Cardiac Shockwave Therapy in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (the CAST-HF trial): study protocol for a randomized controlled trial.

BACKGROUND: Coronary artery diseases (CAD) remains a severe socio-economic burden in the Western world. Coronary obstruction and subsequent myocardial ischemia result in progressive replacement of contractile myocardium with dysfunctional, fibrotic scar tissue. Post-infarctional remodeling is causal for the concomitant decline of left-ventricular function and the fatal syndrome of heart failure. Available neurohumoral treatment strategies aim at the improvement of symptoms. Despite extensive research, therapeutic options for myocardial regeneration, including (stem)-cell therapy, gene therapy, cellular reprogramming or tissue engineering, remain purely experimental. Thus, there is an urgent clinical need for novel treatment options for inducing myocardial regeneration and improving left-ventricular function in ischemic cardiomyopathy. Shockwave Therapy (SWT) is a well-established regenerative tool that is effective for the treatment of chronic tendonitis, long-bone non-union and wound-healing disorders. In preclinical trials, SWT regenerated ischemic myocardium via the induction of angiogenesis and the reduction of fibrotic scar tissue, resulting in improved left-ventricular function. METHODS/DESIGN: In this prospective, randomized controlled, single-blind, monocentric study, 80 patients with reduced left-ventricular ejection fraction (LVEF≤ 40%) are subjected to coronary-artery bypass-graft surgery (CABG) surgery and randomized in a 1:1 ratio to receive additional cardiac SWT (intervention group; 40 patients) or CABG surgery with sham treatment (control group; 40 patients). This study aims to evaluate (1) the safety and (2) the efficacy of cardiac SWT as adjunctive treatment during CABG surgery for the regeneration of ischemic myocardium. The primary endpoints of the study represent (1) major cardiac events and (2) changes in left-ventricular function 12 months after treatment. Secondary endpoints include 6-min Walk Test distance, improvement of symptoms and assessment of quality of life. DISCUSSION: This study aims to investigate the safety and efficacy of cardiac SWT during CABG surgery for myocardial regeneration. The induction of angiogenesis, decrease of fibrotic scar tissue formation and, thus, improvement of left-ventricular function could lead to improved quality of life and prognosis for patients with ischemic heart failure. Thus, it could become the first clinically available treatment strategy for the regeneration of ischemic myocardium alleviating the socio-economic burden of heart failure. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03859466. Registered on 1 March 2019.

A novel mouse model of mild traumatic brain injury using laser-induced shock waves.

Blast-induced mild traumatic brain injury (mild bTBI) has been a frequent battlefield injury in soldiers during the conflicts in Iraq and Afghanistan. Understanding the pathophysiology and determining effective treatments for mild bTBI has become an international problem in the field of neurotrauma research. Contributing to this problem is a lack of an experimental model that accurately mimics the characteristics of mild bTBI. To date, the "mild'' versions of common experimental models of TBI have simply been less severe degrees of traumatic injury; these animals do not necessarily exhibit the clinical characteristics of mild bTBI seen in humans. Therefore, our first objective was to develop a highly controlled mouse model of bTBI using laser-induced shockwaves (LISWs). We established the parameters necessary to cause a reproducible injury of very mild severity, the most important feature seen in clinical practice. We defined very mild bTBI as having no traumatic change on the head visible to the naked eye after the insult was applied using very mild shockwaves to the heads of mice. Our very mild bTBI mouse model exhibited neurobehavioral changes in the chronic phase, such as cognitive impairment and depression-like behavior. We also observed an increase in 5-bromo-2'-deoxyuridine-positive, proliferating cells in the dentate gyrus during the acute phase and a subsequent decrease during the chronic phase. This model appears to be an accurate representation of the damage occurring in actual mild bTBI patients. We also found that an increase in cell proliferation in the dentate gyrus during the acute phase is the most prominent feature after a TBI.

Instant analgesic effect of radial extracorporeal shock wave therapy on primary dysmenorrhoea according to functional magnetic resonance imaging: study protocol for a randomised placebo-controlled trial.

BACKGROUND: Primary dysmenorrhoea (PDM) is defined as a series of pain-dominated symptoms during and after menstruation without organic lesions. Nonsteroidal anti-inflammatory drugs and oral contraceptives are usually recommended as first-line therapy for the clinical treatment of PDM, but their widespread long-term application is controversial. Radial extracorporeal shock wave therapy (rESWT) has been widely applied in musculoskeletal rehabilitation because of its secure and noninvasive characteristics and its confirmed effect in improving pain symptoms. This research seeks to explore the efficacy of rESWT for PDM and the changes in brain function of patients with PDM. METHODS: This clinical research will be a randomised, blind, sham-controlled trial. Thirty-six patients with PDM will be randomly divided into the rESWT group (n = 18) and the sham rESWT group (n = 18). In the rESWT group, treatment will be applied once within 48 h of menstruation at six abdominal myofascial trigger points. The sham rESWT group will receive sham shockwave therapy on the same sites but without energy input. Other dysmenorrhoea-related treatments in both groups will be limited. The main indicators include the short form of the McGill Pain Questionnaire and the Cox Menstrual Symptom Scale. The secondary indicators include the Zung Self-rating Anxiety Scale and Self-rating Depression Scale and functional magnetic resonance imaging (fMRI) changes in brain regions. Results will be evaluated at the screening, at baseline, and before and after treatment, and adverse treatments will be examined. Inter- and intragroup analyses will be performed. DISCUSSION: This randomised controlled study is designed to explore the immediate efficacy of rESWT for PDM. After rESWT treatment, PDM symptom tests and pain tests, as well as fMRI data, will be investigated for the potential connections between immediate neuroanalgesic mechanisms, which are associated with pain and brain networks. The main results will be used to assess the efficacy of rESWT, and secondary results will focus on improving the neurobiological understanding of disease treatment. TRIAL REGISTRATION: China Clinical Trial Register, ChiCTR1900020678. Registered on 13 January 2019.

Radial shockwave therapy for male erectile rejuvenation in a dermatology and/or medical aesthetic practice.

INTRODUCTION: Erectile dysfunction is defined as the inability to achieve and maintain an erection to satisfactorily complete intercourse. Treatment depends on the cause and includes phosphodiesterase 5 inhibitor medications, penile pumps, implants, and surgery. Low-intensity shockwave therapy has been shown to be effective and safe for the treatment of erectile dysfunction. OBJECTIVE: We explored the role of low-intensity radial shockwave therapy for erectile dysfunction treatment in a dermatology and/or medical aesthetic practice setting. MATERIALS AND METHODS: A literature review was conducted on radial low-intensity shockwave technology in use for erectile rejuvenation to explore its positioning, safety, efficacy, tolerability, subject satisfaction, and usability in a dermatology and/or medical aesthetic setting. RESULTS: Low-intensity shockwave therapy was shown to be effective in subjects with organic erectile dysfunction, and the treatment effect was maintained for up to 2 years post-treatment. The treatment is reported to be safe and well-tolerated and have little downtime. Many dermatologists use low-intensity shockwave therapy for the treatment of cellulite and other conditions. This type of treatment is now available for erectile dysfunction and seems an attractive and safe option for subjects with organic vascular erectile dysfunction. CONCLUSIONS: Studies and clinical experience suggest that male erectile rejuvenation using low-intensity radial shockwave therapy seems an attractive option. The treatment can be safely, and effectively, delivered by trained staff as part of the total package that is available to men in a dermatology and/or medical aesthetic practice.

Survival of Extremotolerant Bacteria from the Mukundpura Meteorite Impact Crater.

Carbonaceous meteorites provide clues with regard to prebiotic chemistry and the origin of life. Geological Survey of India recorded a carbonaceous chondrite meteorite fall in Mukundpura, India, on June 6, 2017. We conducted a study to investigate the microbial community that survived the meteorite impact. 16S rRNA metagenomic sequencing indicates the presence of Actinobacteria, Proteobacteria, and Acidobacteria in meteorite impact soil. Comparative phylogenetic analysis revealed an intriguing abundance of class Bacilli in the impact soil. Bacillus thermocopriae IR-1, a moderately thermotolerant organism, was isolated from a rock, impacted by the Mukundpura meteorite. We investigated the resilience of B. thermocopriae IR-1 to environmental stresses and impact shock in a Reddy shock tube. Bacillus thermocopriae IR-1 survived (28.82% survival) the effect of shock waves at a peak shock pressure of 300 kPa, temperature 400 K, and Mach number of 1.47. This investigation presents the first report on the effect of impact shock on B. thermocopriae IR-1. The study is also the first report on studying the microbial diversity and isolation of bacteria from impact crater soil immediately after meteorite impact event.

Effective noninvasive body contouring by using a combination of cryolipolysis, injection lipolysis, and shock waves.

BACKGROUND: Cryolipolysis combined with shockwave therapy has been previously shown to have synergistic effects in body contouring results. OBJECTIVE: This open-label, prospective, multicenter, comparative study investigated the safety and efficacy of combined cryolipolysis, shockwave therapy with cryolipolysis, shockwave therapy, and injection polyenylphosphatidylcholine-based lipolysis. METHODS: Enrolled patients were treated in the abdominal or flank area with cryolipolysis, shockwave therapy and injection lipolysis (n = 10) or cryolipolysis and shockwave therapy (n = 4). All treatments were conducted the same day. Evaluations were conducted 3 months after treatment and included histological analysis, standardized photography, blinded-investigator efficacy, and safety ratings, as well as patient ratings of satisfaction and tolerance. RESULTS: Compared to baseline, the 3-month follow-up histological analysis revealed a more profound subcutaneous adipose tissue reaction with the triple combination therapy (cryolipolysis, injection lipolysis, radial shock wave) than with the double combination with regard to adipocyte damage and grade of inflammation. Waist circumference was significantly reduced in patients of both groups, but patients in the triple combination group were shown to have a significantly more pronounced reduction in subcutaneous fat. Factors that were shown to influence treatment outcome included baseline BMI and waist circumference. Age and gender had no effect. The abdominal area reacted better to the treatment compared to flanks. No significant side effects or adverse events were reported. The procedure was well-tolerated, and the majority of patients were satisfied with the treatment results. CONCLUSIONS: Combination of cryolipolysis, radial shockwave, and injection lipolysis is a safe, well-tolerated treatment for reduction in subcutaneous fat.

Marine Mammal Lung Dynamics when Exposed to Underwater Explosion Impulse.

Very little is known about marine mammal susceptibility to primary blast injury (PBI) except in rare cases of opportunistic studies. As a result, traditional analysis techniques relied on methods developed more than 30 years ago using terrestrial mammals as surrogates. Modeling tools available today have the computing power to vastly improve calculation of safe ranges and injury zones from underwater explosions (UNDEX) employing morphologically accurate proxies with material properties similar to marine mammal tissues. The Dynamic System Mechanics Advanced Simulation (DYSMAS) fluid-structure interaction (FSI) software is being used to simulate the complex phenomena of UNDEX, shock wave, and bubble pulse propagation through the water and transmission of energy to a cetacean focusing on the dynamic response of the thoracic cavity and air-filled lungs to a shock wave. The approach integrates fluid and structural analyses with the material properties of blubber, bone, and muscle using marine mammal morphometrics to eliminate unnecessary assumptions made during more traditional approaches to analysis developed before these types of data and computational power were available. DYSMAS analyses of a 1D gas bubble surrounded by water was found to closely match the classical bubble dynamics models. Further, DYSMAS models of a spherical gas bubble surrounded by tissue and rib structure demonstrate a global radial oscillation of the gas bubble, but also show significant local deflection and material strain in response to the UNDEX loading. The intended result of the investigation is an improved and scientifically defensible understanding of the effects of UNDEX on marine mammals. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 302:718-734, 2019. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Shock waves increase pulmonary vascular leakage, inflammation, oxidative stress, and apoptosis in a mouse model.

Severe lung damage is a major cause of death in blast victims, but the mechanisms of pulmonary blast injury are not well understood. Therefore, it is important to study the injury mechanism of pulmonary blast injury. A model of lung injury induced by blast exposure was established by using a simulation blast device. The effectiveness and reproducibility of the device were investigated. Eighty mice were randomly divided into eight groups: control group and 3 h, 6 h, 12 h, 24 h, 48 h, 7 days and 14 days post blast. The explosive device induced an explosion injury model of a single lung injury in mice. The success rate of the model was as high as 90%, and the degree of lung injury was basically the same under the same pressure. Under the same conditions, the thickness of the aluminum film can be from 0.8 mm to 1.6 mm, and the peak pressure could be from 95.85 ± 15.61 PSI to 423.32 ± 11.64 PSI. There is no statistical difference in intragroup comparison. A follow-up lung injury experiment using an aluminum film thickness of 1.4 mm showed a pressure of 337.46 ± 18.30 PSI induced a mortality rate of approximately 23.2%. Compared with the control group (372 ± 23 times/min, 85.9 ± 9.4 mmHg, 4.34 ± 0.09), blast exposed mice had decreased heart rate (283 ± 21 times/min) and blood pressure (73.6 ± 3.6 mmHg), and increased lung wet/dry weight ratio(2.67 ± 0.11), marked edematous lung tissue, ruptured blood vessels, infiltrating inflammatory cells, increased NF-κB (4.13 ± 0.01), TNF-α (4.13 ± 0.01), IL-1ß (2.43 ± 0.01) and IL-6 (4.65 ± 0.01) mRNA and protein, decreased IL-10(0.18 ± 0.02) mRNA and protein ( P < 0.05). The formation of ROS and the expression of MDA5 (4.46 ± 0.01) and IREα (3.43 ± 0.00) mRNA and protein were increased and the expression of SOD-1 (0.28 ± 0.02) mRNA and protein was decreased ( P < 0.05). Increased expression of Bax (3.54 ± 0.00) and caspase 3 (4.18 ± 0.01) mRNA and protein inhibited the expression of Bcl-2 (0.39 ± 0.02) mRNA and protein. The changes of pulmonary edema, inflammatory cell infiltration, and cell damage factor expression increased gradually with time, and reached the peak at 12-24 h after the outbreak, and returned to normal at 7-14 days. Detonation injury can lead to edema of lung tissue, pulmonary hemorrhage, rupture of pulmonary vessels, induction of early inflammatory responses accompanied by increased oxidative stress in lung tissue cells and increased apoptosis in mice experiencing blast injury. The above results are consistent with those reported in other literatures. It is showed that the mouse lung blast injury model is successfully modeled, and the device can be used for the study of pulmonary blast injury. Impact statement The number of patients with explosive injury has increased year by year, but there is no better treatment. However, the research on detonation injury is difficult to carry out. One of the factors is the difficulty in making the model of blast injury. The laboratory successfully developed and produced a simulation device of explosive knocking through a large amount of literature data and preliminary experiments, and verified the preparation of the simulation device through various experimental techniques. The results showed that the device could simulate the shock wave-induced acute lung injury generated, which was similar to the actual knocking injury. The experimental process was controlled. Under the same condition, there was no statistical difference between the groups. It is possible to realize miniaturization and precision of an explosive knocking simulation device, which is a good experimental tool for further research on the mechanism of organ damage caused by detonation and the development of protective drugs.

Hypothermia ameliorates blast-related lifespan reduction of C. elegans.

Blast-related mild traumatic brain injury induces significant long-term health issues, yet treatment procedures remain underdeveloped. Therapeutic hypothermia has been postulated as a potentially effective therapy. In a Caenorhabditis elegans model, we demonstrate a dose-dependent reduction in lifespan following exposure to blast-like shock waves. Using polyvinyl alcohol, we show that cavitation is a key injurious factor in the damaging shock wave component. Short and long lifespan C. elegans mutants demonstrated the interaction of genetic and environmental longevity-determining factors. Hypothermia reduced the long term effect of shock wave exposure. Thus, we present an effective C. elegans model of long term effects of blast-related mild traumatic brain injury, as well as evidence of the merit of therapeutic hypothermia as a therapy option following blast exposure.

A randomized, triple-blind trial of cardiac shock-wave therapy on exercise tolerance and symptoms in patients with stable angina pectoris.

BACKGROUND: Despite major advances in managing coronary artery disease and continuous research on alternative techniques to enhance myocardial perfusion and reduce symptoms, coronary artery disease is still one of the leading causes of adult disability worldwide. Cardiac shock-wave therapy (CSWT) has shown promising results in the amelioration of myocardial ischemia in experimental studies; however, clinical results are limited to single-center, mostly uncontrolled and underpowered trials. The current study aimed to evaluate whether CSWT can improve exercise tolerance and relieve angina symptoms in addition to optimal medical treatment in patients with stable angina. PARTICIPANTS AND METHODS: A prospective, randomized, triple blind, sham-procedure-controlled study was carried out. The primary endpoint was total exercise duration in the modified Bruce treadmill test at the 6-month follow-up. The secondary endpoints were changes in ST-segment depression during the treadmill test, angina symptoms during the treadmill test, number of angina attacks per week, number of sublingual nitroglycerin consumption per week, Canadian Cardiovascular Society angina functional class, and the Seattle Angina Questionnaire score at the 6-month follow-up. Patients were randomized at a 1 : 1 ratio to optimal medical plus cardiac shock-wave therapy (OMT+CSWT) and optimal medical therapy with sham procedure (OMT+placebo) groups. RESULTS: The mean exercise time improved in both study arms - CSWT and placebo treatment - at the 3- and 6-month follow-up, without a significant difference between groups. The magnitude and frequency of peak exercise ST-segment depression reduced significantly in the CSWT+OMT group compared with the OMT+placebo group at the 6-month follow-up (51.4 vs. 90.6%, P=0.001). Percentage of angina-free patients increased progressively in both groups throughout the study. The Seattle Angina Questionnaire scores improved significantly in both arms for four of five domains at the 3- and the 6-month follow-up. Numerically, although insignificant, the decrease in the number of angina episodes was more prominent in the OMT+CSWT group compared with the OMT+placebo group. CONCLUSION: The total exercise duration in the modified Bruce treadmill test at the 6-month follow-up did not differ significantly in patients treated with CSWT compared with optimal medical therapy alone. In addition, CSWT exerted a neutral effect on the quality of life and level of angina.

Effective testing of personal protective equipment in blast loading conditions in shock tube: Comparison of three different testing locations.

We exposed a headform instrumented with 10 pressure sensors mounted flush with the surface to a shock wave with three nominal intensities: 70, 140 and 210 kPa. The headform was mounted on a Hybrid III neck, in a rigid configuration to eliminate motion and associated pressure variations. We evaluated the effect of the test location by placing the headform inside, at the end and outside of the shock tube. The shock wave intensity gradually decreases the further it travels in the shock tube and the end effect degrades shock wave characteristics, which makes comparison of the results obtained at three locations a difficult task. To resolve these issues, we developed a simple strategy of data reduction: the respective pressure parameters recorded by headform sensors were divided by their equivalents associated with the incident shock wave. As a result, we obtained a comprehensive set of non-dimensional parameters. These non-dimensional parameters (or amplification factors) allow for direct comparison of pressure waveform characteristic parameters generated by a range of incident shock waves differing in intensity and for the headform located in different locations. Using this approach, we found a correlation function which allows prediction of the peak pressure on the headform that depends only on the peak pressure of the incident shock wave (for specific sensor location on the headform), and itis independent on the headform location. We also found a similar relationship for the rise time. However, for the duration and impulse, comparable correlation functions do not exist. These findings using a headform with simplified geometry are baseline values and address a need for the development of standardized parameters for the evaluation of personal protective equipment (PPE) under shock wave loading.

Intracochlear pressure measurements during acoustic shock wave exposure.

INTRODUCTION: Injuries to the peripheral auditory system are among the most common results of high intensity impulsive acoustic exposure. Prior studies of high intensity sound transmission by the ossicular chain have relied upon measurements in animal models, measurements at more moderate sound levels (i.e. < 130 dB SPL), and/or measured responses to steady-state noise. Here, we directly measure intracochlear pressure in human cadaveric temporal bones, with fiber optic pressure sensors placed in scala vestibuli (SV) and tympani (ST), during exposure to shock waves with peak positive pressures between ∼7 and 83 kPa. METHODS: Eight full-cephalic human cadaver heads were exposed, face-on, to acoustic shock waves in a 45 cm diameter shock tube. Specimens were exposed to impulses with nominal peak overpressures of 7, 28, 55, & 83 kPa (171, 183, 189, & 192 dB pSPL), measured in the free field adjacent to the forehead. Specimens were prepared bilaterally by mastoidectomy and extended facial recess to expose the ossicular chain. Ear canal (EAC), middle ear, and intracochlear sound pressure levels were measured with fiber-optic pressure sensors. Surface-mounted sensors measured SPL and skull strain near the opening of each EAC and at the forehead. RESULTS: Measurements on the forehead showed incident peak pressures approximately twice that measured by adjacent free-field and EAC entrance sensors, as expected based on the sensor orientation (normal vs tangential to the shock wave propagation). At 7 kPa, EAC pressure showed gain, calculated from the frequency spectra, consistent with the ear canal resonance, and gain in the intracochlear pressures (normalized to the EAC pressure) were consistent with (though somewhat lower than) previously reported middle ear transfer functions. Responses to higher intensity impulses tended to show lower intracochlear gain relative to EAC, suggesting sound transmission efficiency along the ossicular chain is reduced at high intensities. Tympanic membrane (TM) rupture was observed following nearly every exposure 55 kPa or higher. CONCLUSIONS: Intracochlear pressures reveal lower middle-ear transfer function magnitudes (i.e. reduced gain relative to the ear canal) for high sound pressure levels, thus revealing lower than expected cochlear exposure based on extrapolation from cochlear pressures measured at more moderate sound levels. These results are consistent with lowered transmissivity of the ossicular chain at high intensities, and are consistent with our prior report measuring middle ear transfer functions in human cadaveric temporal bones with high intensity tone pips.

Changes in [18F]Fluorodeoxyglucose Activities in a Shockwave-Induced Traumatic Brain Injury Model Using Lithotripsy.

We present a longitudinal study of cerebral metabolism using [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a rat model of shockwave-induced traumatic brain injury (SW-TBI). Anesthetized rats received 5 or 10 SW pulses to the right anterior lateral or dorsal frontal regions using SW lithotripsy. Animals were scanned for FDG uptake at baseline, 3 h post-injury, and 3 days post-injury, using a small animal PET/computed tomography (CT) scanner. FDG uptake at all time-points was quantified as the ratio of brain activity relative to peripheral activity in the left ventricle (LV) in the heart (Abrain/ALV) for the entire brain, each hemisphere, and four cortices (motor, cingulate, somatosensory, and retrosplenial). The mixed-designed models analysis of variance (ANOVA) for the hemispheric and global FDG uptake ratio showed a significant effect of the time-of-scan (p = 0.038) and measured region (p = 6.12e-09). We also observed a significant effect of the time-of-scan (p = 0.046) and measured region (p = 2.28e-09) for the FDG uptake ratio in four cortical regions. None of the measurements (global or local) showed a significant effect for the number of SW pulses (5 or 10) or SW location (lateral or dorsal frontal regions). Our data suggest that SW-TBI causes hypermetabolism on the impact side of the rat brain at 3 h post-injury compared with the baseline measurements. However, the increase in FDG uptake by day 3 post-injury was not significant. Further studies on post-TBI metabolic changes are needed to understand better the pathophysiology of the injury.

Impact of repeated extracorporeal shock wave lithotripsy on prepubertal rat kidney.

This study aimed to investigate the effects of repeated extracorporeal shock wave lithotripsy (ESWL) on the kidneys of prepubertal and adult rats. Thirty rats were used: 15 were prepubertal (3 weeks of age) with an average body weight of 72.3 ± 3.3 g, and 15 were adults with of 265 ± 11.3 g. The prepubertal and adult rats were separately and randomly allocated to three groups, each consisting of five rats. Following anesthetization, the left kidney of each rat in each group received shock waves in one, two, or three sessions separated by 72 h. The rats in each group were killed 72 h after the last ESWL session, and both kidneys were harvested; the right kidney was used as the control. Renal injury was examined with histological analysis, immunohistochemistry, and Western blot to detecting the expression of heat-shock protein-70, tumor necrosis factor-alpha-α, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 as markers of renal damage. All of these markers were similarly increased with increased ESWL sessions in both age groups. Histological analysis revealed more serious fibrosis and inflammation in the ESWL-treated kidneys in both groups than in the controls, with the damage increasing with increasing numbers of sessions. ESWL on the kidney increased renal damage according to the number of sessions in both age groups of rats, and the effects of ESWL on renal injury were similar in the two groups. However, there were generally no significant differences in the effects of ESWL on molecular indicators of renal injury between prepubertal and adult rats.