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Infrasound induces coronary perivascular fibrosis in rats
Abstract
Background
Chronic exposure to industrial noise is known to affect biological systems, namely, by inducing fibrosis in the absence of inflammatory cells. In rat hearts exposed to this environmental hazard, we have previously found myocardial and perivascular fibrosis. The acoustic spectrum of industrial environments is particularly rich in high-intensity infrasound (<20 Hz), whose effects on the heart are unknown. We evaluated the morphological changes induced by IFS in rat coronaries in the presence and absence of dexamethasone.
Methods
Adult Wistar rats were divided into three groups: group A (GA)—IFS (<20 Hz, 120 dB)-exposed rats for 28 days treated with dexamethasone; group B (GB)—IFS-exposed rats; group C (GC)—age-matched controls. The midventricle was prepared for observation with an optical microscope using 100× magnification. Thirty-one arterial vessels were selected (GA 8, GB 10, GC 13). The vessel caliber, thickness of the wall, and perivascular dimensions were quantified using image J software. Mann–Whitney and Kruskal–Wallis tests were used to compare the groups for lumen-to-vessel wall (L/W) and vessel wall-to-perivascular tissue (W/P) ratios.
Results
IFS-exposed rats exhibited a prominent perivascular tissue. The median L/W and median W/P ratios were 0.54 and 0.48, 0.66 and 0.49, and 0.71 and 0.68, respectively, in GA, GB, and GC. The W/P ratio was significantly higher in GC compared with IFS-exposed animals (P=.001). The difference was significant between GC and GB (P=.008) but not between GC and GA.
Conclusion
IFS induces coronary perivascular fibrosis that differs under treatment with corticosteroid.
... 15 Furthermore, it has been demonstrated that infrasound (2À20 Hz, 114 dB) causes perivascular coronary sclerosis in rats by induction of inflammation. 16 This effect might be triggered via inactivation of the PPARy (peroxisome proliferator-activated receptor-gamma) signaling pathway. 17 Infrasound/low-frequency noise (13À30 Hz, 14 dB) has been shown to impair the integrity of erythrocytes of rats due to increased membrane permeability. ...
... Nevertheless, it is known that infrasound can harm healthy cells by causing cell stress, inflammation, apoptosis, and damaging the cells' ultrastructure. 15,16,17,19,20,21,22,À23 Therefore, it becomes apparent that infrasound can take effect on malignant cells as well. All currently accessible studies involving the direct use of infrasound in cancer studies are presented and discussed below. ...
... 1,31,32 Nonetheless, it has been shown several times that infrasound can cause changes in cells' ultrastructure with functional consequences, inflammation, fibrosis, and maybe even cell death. 15,16,20,21,24,28,29,33 It is of great interest, whether these harmful effects of infrasound may also offer a new perspective in cancer treatment. There is only a small number of studies investigating the influence of infrasound on cancer cells. ...
Background
: Researchers take different positions when describing the effects of infrasound on the human body. Although several studies investigated the likely harmful effects of infrasound exposure from wind turbines a significant connection has not been found yet. There is evidence that infrasound interacts with cell metabolism and may disrupt cell membrane integrity.
Objectives
: The suggested impairment of the cells’ ultrastructure by infrasound leads to the question of whether infrasound can be therapeutically used, for instance in cancer therapy. This review provides the current state of the literature.
Method
: Current literature on infrasound in cancer therapy including all studies with the search terms ‘cancer’ and ‘infrasound’ were identified and reviewed until the year 2020.
Results
: The present state of research reveals promising effects of targeted infrasound in cancer therapy. Infrasound directly affects the tumor cells’ ultrastructure and seems to sensitize several types of cancer to chemotherapy, presumably due to membrane permeabilization. The application of infrasound on tumor cells without other therapeutic agents demonstrates different effects that probably depend on the type of cells, the applied frequency and sound pressure level as well as the time of exposure.
Conclusions
: The mechanism of infrasound on cancer cells is not completely understood yet, hence, further studies have to be conducted to clarify the ultrastructural and metabolic changes inside the tumor cells. The development of suitable infrasound generators for the application in a clinical setting would be an important course of action.
... The evidence for this is supported by the responsiveness of endothelial mechano-sensors for external influences such as gravity, pressure, swelling, noise [1] [3] [22] [30] as well as the microtactile excitability of endothelial cells [5]. There is also evidence that infrasound interacts with cell metabolism and leads to perivascular fibrosis in Infrasound induces coronary perivascular fibrosis in rats according to Lousinha (2018) [52]. Similar findings are presented in [53] [54] [55]. ...
... Das Myokard der Tiere wies darüber hinaus im Vergleich zu nichtexponierten Tieren eine höhere Zahl apoptotischer Zellen auf [45,46]. Außerdem wurde eine Zunahme perivaskulärer Koronarsklerose nach Exposition von Ratten gegenüber Infraschall mit einem Schalldruckpegel von 120 dB nachgewiesen [47]. Infraschallexposition kann weiteren Studien zufolge zur Destabilisierung von Zellwänden führen. ...
Infrasound describes ubiquitous, low-frequency sound (< 20 Hz) in the environment with a long wavelength below the median hearing threshold, which can nevertheless be heard and tactilely perceived, depending on the sound pressure level and frequency spectrum. In nature, infrasound emissions usually occur only in the low-threshold range. Nevertheless, after strong and chronic exposure to usually artificially generated infrasound emissions, various effects on the ear and the body, sometimes questionably critical to health, can be observed. Correct measurement and assessment of infrasound sources is complex and controversial. Established guidelines are scarce. Innovative research areas include infrasound monitoring for evaluation of natural events and infrasound applications in medicine. In the future, it is hoped that new insights will be gained from infrasound research and that a more extensive classification in occupational medicine will be possible.
... Introduction: Recent data has shown a significant association between noise exposure and atrial fibrillation (AF) in a large cohort [1] but the pathophysiology remains unclear. The acoustic spectrum of industrial environments is particularly rich in high-intensity infrasound (IFS), which we have previously found to induce coronary perivascular fibrosis in rat hearts [2][3][4]. The role of atrial fibrosis in AF is well documented and remains the cornerstone of atrial pathology in patients with this arrhythmia [5]. ...
Introduction Recent data has shown a significant association between noise exposure and atrial fibrillation (AF) in a large cohort [1] but the pathophysiology remains unclear. The acoustic spectrum of industrial environments is particularly rich in high-intensity infrasound (IFS), which we have previously found to induce coronary perivascular fibrosis in rat hearts [2–4]. The role of atrial fibrosis in AF is well documented and remains the cornerstone of atrial pathology in patients with this arrhythmia [5]. The aim of this study was to evaluate and measure the atrial interstitial fibrosis in rats exposed to high-intensity IFS.Material and methods Twelve Wistar rats exposed to high-intensity IFS (110 dB
... High-intensity infrasound exposure. High-intensity infrasound exposure was performed as previously published 52 . In short, pseudo-random waveform in the 2 to 20 Hz decade band was designed with Matlab based on a bandpass-filtered 30-s maximum length sequence segment. ...
Recent focus has been given on the effects of high-intensity infrasound (HII) exposure, and whether it induces changes in pancreatic morphology and glucose metabolism is still unknown. As such, we have studied the impact of HII exposure on glucose tolerance, insulin sensitivity, pancreatic islet morphology, muscle GLUT4 and plasma insulin and corticosterone levels. Normal and glucose intolerant wild-type Wistar rats were randomly divided in two groups: one group not exposed to HII and the other continuously exposed to HII. Animals were sacrificed at three timepoints of exposure (1, 6 or 12 weeks). An intraperitoneal glucose tolerance test was performed, blood samples were collected and the pancreas and the quadriceps femoris muscle were excised. Circulating insulin and corticosterone levels were determined and pancreatic and muscular tissue were routinely processed for histochemistry and immunohistochemistry with an anti-GLUT4 antibody. Animals exposed to HII had higher corticosterone levels than animals not exposed. No differences were found on insulin concerning HII exposure or glucose intolerance. Glucose intolerant animals had pancreatic islet fibrosis and no differences were found in GLUT4 ratio concerning HII exposure. In conclusion, we found that continuous exposure to HII increases stress hormone levels without inducing glucose intolerance in rats.
... Another underlying mechanism for the damage induced by infrasound is the oxidative stress, which was also investigated by the same team, who found the expression of CAT, GPx, SOD1 and SOD2 and their activities in rat cardiomyocytes in infrasound exposure groups were significantly decreased compared to controls, along with significantly higher levels of O 2 and H 2 O 2 . [27] Further, Lousinha et al. [28] showed that exposure to 90 to 145dB infrasound induces coronary perivascular fibrosis in rats. It is worth mentioning here that Pei et al. used very high level of Infrasound (130 dB) in their experiments to induce these effects. ...
Background:
Human exposure to infrasound is increasing due to man-made factors, such as occupational conditions, wind farms and transportation. The concern among the public regarding the safety of infrasound exposure is growing.
Aims:
To evaluate whether exposure to infrasound interferes directly with human cardiac function and contributes to pathological processes.
Setting:
The University Hospital of Mainz, Germany.
Methods:
Human myocardial tissues, obtained from patients undergoing cardiac surgery, were prepared in small muscle samples and stimulated electrically in-vitro for a period of almost two hours under physiological conditions to induce continuous pulsatile contractions and simulating a working human heart. Two samples were obtained from each donor: one was subjected to infrasound for 60 min and the other served as a control. Their contraction forces (CF) and durations (CD) were measured before and after each testing period and their relative changes (CF% and CD%) were calculated and introduced in a multilinear regression model. The following three infrasound levels of exposure were used in this study: 100, 110 and 120 dBz.
Results:
The measured CF% corresponded negatively with the infrasound level measured in dBz (R2 = 0.631; P = 0.018). The decrease measured almost -11% at 110 dBz and -18% at 120 dBz, after correction for control. The CD on the other hand remained unchanged.
Conclusions:
Exposure to high levels of infrasound (more than 100 dBz) interferes with cardiac muscle contractile ability, as early as one hour after exposure. There are numerous additional studies which support this conclusion. These results should be taken into account when considering environmental regulations.
... There is evidence from high-intensity infrasound exposure studies in laboratory animals that chronic exposure results in proliferation of the connective tissue matrix and collagen fibers in animals; this fibrotic response has been documented in several organs, such as the heart, lung and glands of rats chronically exposed to industrial-type noise [27,28,29,30]. Oliveira et al. [31] documented the same alterations in the liver connective tissue, on centrolobular regions without disruption of the organ architecture, as a result of the exposure to high-intensity infrasound. ...
Previous experimental studies show that exposure to noise with high and audible frequencies causes multiple metabolic alterations, such as increased liver glycogen and triglycerides. However, the effect of exposure to sound with lower frequencies, such as high-intensity infrasound (frequency <20 Hz and sound pressure level >90 dB), on the liver lipid content is still unclear. As such, we aimed to study the effect of exposure to high-intensity infrasound of both normal and glucose intolerant rats on the liver lipid content. For this study, 79 wild-type male Wistar rats were randomly divided into two groups: G1, no treatment, and G2, induced glucose intolerance. Each of these two groups was randomly divided in two subgroups: s (animals kept in silence) and i (animals continuously exposed to high-intensity infrasound noise). At three noise-exposure time-points (1, 6 and 12 weeks) the rats were sacrificed, the liver was excised and hepatic lipids extracted. Data analysis was performed using a two-way ANOVA (p = 0.05). No significant effects due to interactions between the several factors exist on the liver lipid content (p=0.077). Moreover, no significant effects due to infrasound exposure (p=0.407) or glucose tolerance status (p=0.938) were observed. Our study shows that continuous exposure to high-intensity infrasound has no influence on the lipid content of the liver of both normal and glucose intolerant animals. This finding reinforces the need for further experimental studies on the physiological effects of infrasound due to its possible hazardous effects on human health.
... No changes were observed in the lumen-to-wall ratio. With dexamethasone treatment and exposure, no differences were observed in the wall-to-perivascular-space ratio, as compared to controls, suggesting an underlying inflammatory mechanism [46]. ...
Within the context of noise-induced health effects, the impact of airborne acoustical phenomena on biological tissues, particularly within the lower frequency ranges, is very poorly understood. Although the human body is a viscoelastic-composite material, it is generally modeled as Hooke elastic. This implies that acoustical coupling is considered to be nonexistent at acoustical frequencies outside of the human auditory threshold. Researching the acoustical properties of mam-malian tissue raises many problems. When tissue samples are investigated as to their pure mechanical properties, stimuli are not usually in the form of airborne pressure waves. Moreover, since the response of biological tissue is dependent on frequency, amplitude, and time profile, precision laboratory equipment and relevant physiological endpoints are mandatory requirements that are oftentimes difficult to achieve. Drawing upon the viscoelastic nature of biological tissue and the tensegrity model of cellular architecture, this chapter will visit what is known to date on the biological response to a variety of different acoustic stimuli at very low frequencies.
... Another underlying mechanism for the damage induced by infrasound is the oxidative stress, which was also investigated by the same team, who found the expression of CAT, GPx, SOD1 and SOD2 and their activities in rat cardiomyocytes in infrasound exposure groups were significantly decreased compared to controls, along with significantly higher levels of O 2 and H 2 O 2 . [27] Further, Lousinha et al. [28] showed that exposure to 90 to 145dB infrasound induces coronary perivascular fibrosis in rats. It is worth mentioning here that Pei et al. used very high level of Infrasound (130 dB) in their experiments to induce these effects. ...
The zoo soundscape has a number of important implications for animal welfare, management, and conservation. However, despite its importance, the zoo soundscape is yet to be examined in depth using multiple measures. Consistent human presence can influence the zoo soundscape. However, it is difficult to determine the specific impact of human presence, as visitors are usually present during the day when animals are active. The COVID-19 lockdown in 2020 provided a unique opportunity to study zoo soundscapes in the absence of visitors. We compared the sound environment during the 2020 closure period to a comparable open period in 2019 across three zoo aviaries, examining broad band frequency measures of sound pressure levels, sound pressure levels in defined frequency bands, and acoustic indices (Acoustic Complexity Index and Normalized Difference Soundscape Index) to describe the zoo soundscape. Acoustic indices have not, to our knowledge, previously been used in the zoo setting, although they may provide a useful metric to assess sound disturbance. Therefore, we also used this natural experiment to explore how successful these measures may be in assessing disturbances in captive environments. We found a significant effect of human presence on the sound environment; aviaries were generally quieter with less low frequency noise and with a greater proportion of biotic sound during the 2020 zoo closure period. We argue that NDSI could be a useful index for determining anthropogenic disturbance in zoos, although further information on how it is influenced by additional factors, such as human speech, would be beneficial. The use of multiple measures to assess the sound environment in zoos can provide additional information beyond 'loudness', such as frequencies where sound energy is concentrated and characteristics of the soundscape, which could be used to better target management and mitigation.
Morphological changes induced by industrial noise have been experimentally observed in several organs. This study aims to characterize the effect of industrial noise on the pulp cell density of Wistar rats from a histological point of view, through qualitative and quantitative analysis. The histologic sections were observed over the optical microscope and photographed using 10x and 40x magnifications and analyzed using an image processing software. They refer to a group of animals exposed to industrial noise for 3 months and for 7 months (EG) and another group of animals kept in silence for control (CG) during the same periods. There was a significant decrease in pulp cell density in teeth of the animals exposed for 3 months when compared to control teeth group (p = 0.01). However, in the group exposed for 7 months, no statistically significant differences were found (p = 0.66). Even so, we found an evident relationship between exposure to industrial noise and teeth morphological changes. The observed changes are similar to the modifications found on aged teeth. Therefore, this study places industrial noise as an aggressive stimulus that can cause a reaction of the pulp-dentin complex with morphological changes compatible with premature aging of the tooth.
Environmental exposures represent a significant health hazard, which cumulatively may be
responsible for up to 2/3 of all chronic non-communicable disease and associated
mortality (Global Burden of Disease Study and The Lancet Commission on Pollution
and Health), which has given rise to a new concept of the exposome: the sum of
environmental factors in every individual’s experience. Noise is part of the exposome
and is increasingly being investigated as a health risk factor impacting neurological,
cardiometabolic, endocrine, and immune health. Beyond the well-characterized effects
of high-intensity noise on cochlear damage, noise is relatively well-studied in the
cardiovascular field, where evidence is emerging from both human and translational
experiments that noise from traffic-related sources could represent a risk factor for
hypertension, ischemic heart disease, diabetes, and atherosclerosis. In the present
review, we comprehensively discuss the current state of knowledge in the field of
noise research. We give a brief survey of the literature documenting experiments in
noise exposure in both humans and animals with a focus on cardiovascular disease.
We also discuss the mechanisms that have been uncovered in recent years that describe
how exposure to noise affects physiological homeostasis, leading to aberrant redox
signaling resulting in metabolic and immune consequences, both of which have
considerable impact on cardiovascular health. Additionally, we discuss the molecular
pathways of redox involvement in the stress responses to noise and how they manifest in
disruptions of the circadian rhythm, inflammatory signaling, gut microbiome composition,
epigenetic landscape and vessel function.
Introduction
An anatomical observational, retrospective and cross-sectional study of the Venotomographies performed at CIMED was carried out from January 2014 to the present, with 105 studies of patients of both sexes. The study methodology was multislice computed venotomography, which allowed to achieve a live anatomical study in several observational planes and making virtual dissections. The aim is demonstrating by means of virtual anatomy how the reticular hypodermic venous system (RHVS) connects the main superficial venous trunks to each other, to the perforating venous system and through them to the deep venous system.
Materials and methods
The scanner used was a 64-detector Phillips multislice tomograph and the program chosen was Phillips' IntelliSpace Portal. To determine the characteristics of RHVS, it was divided the studied population into three groups: 1- without venous pathology, 2- with venous hypertension due to obstruction or compression, 3- in varicose recurrence.
Results
The procedure used allowed to demonstrate that the RHVS produces a true integration of the entire superficial venous system, perforating venous system and through this to the deep venous system as well. Discussion and conclusions: The MCVT has proven to be a versatile and effective method of observing the entire superficial venous system in detail. The RHVS integrates both truncal venous systems, saphenous vein magna, saphenous vein parva and its main tributaries. It integrates all perforating veins with the reticular venous system. And it links the superficial venous system and the perforator with the deep venous system. This conclude affirming that the entire superficial venous system is a single anatomical unit integrated by the RHVS.
Epidemiological studies have found that transportation noise increases the risk of cardiovascular morbidity and mortality, with high-quality evidence for ischaemic heart disease. According to the WHO, ≥1.6 million healthy life-years are lost annually from traffic-related noise in Western Europe. Traffic noise at night causes fragmentation and shortening of sleep, elevation of stress hormone levels, and increased oxidative stress in the vasculature and the brain. These factors can promote vascular dysfunction, inflammation and hypertension, thereby elevating the risk of cardiovascular disease. In this Review, we focus on the indirect, non-auditory cardiovascular health effects of transportation noise. We provide an updated overview of epidemiological research on the effects of transportation noise on cardiovascular risk factors and disease, discuss the mechanistic insights from the latest clinical and experimental studies, and propose new risk markers to address noise-induced cardiovascular effects in the general population. We also explain, in detail, the potential effects of noise on alterations of gene networks, epigenetic pathways, gut microbiota, circadian rhythm, signal transduction along the neuronal–cardiovascular axis, oxidative stress, inflammation and metabolism. Lastly, we describe current and future noise-mitigation strategies and evaluate the status of the existing evidence on noise as a cardiovascular risk factor.
Background:
Noise is an important environmental risk factor. Industrial environments are rich in high-intensity infrasound (hi-IFS), which we have found to induce myocardial and coronary perivascular fibrosis in rats. The effects of exposure to IFS on the ventricles have been studied, but not on the atria. We hypothesized that rats exposed to hi-IFS develop atrial remodeling involving fibrosis and connexin 43, which we sought to evaluate.
Material and methods:
Seventy-two Wistar rats, half exposed to hi-IFS (120 dB, <20 Hz) during a maximum period of 12 weeks and half age-matched controls, were studied. Atrial fibrosis was analyzed by Chromotrope-aniline blue staining. The immunohistochemical evaluation of Cx43 was performed using the polyclonal antibody connexin-43 m diluted 1:1000 at 4 °C overnight. Digitized images were obtained with an optical microscope using 400× magnifications. The measurements were performed using image J software. A two-way ANOVA model was used to compare the groups.
Results:
The mean values of the ratio "atrial fibrosis / cardiomyocytes" increased to a maximum of 0.1095 ± 0,04 and 0.5408 ± 0,01, and of the ratio "CX43 / cardiomyocytes" decreased to 0.0834 ± 0,03 and 0.0966 ± 0,03, respectively in IFS-exposed rats and controls. IFS-exposed rats exhibited a significantly higher ratio of fibrosis (p < .001) and lower ratio of Cx43 (p = .009).
Conclusion:
High-intensity infrasound exposure leads to an increase in atrial interstitial fibrosis and a decrease in connexin 43 in rat hearts. This finding reinforces the need for further experimental and clinical studies concerning the effects of exposure to infrasound.
Cardiac fibroblasts are activated by mechanical stress, but the underlying mechanisms involved remain poorly understood. In this study, we investigated whether focal adhesion kinase (FAK) plays a role in the activation of cardiac fibroblasts in response to cyclic stretch.
Neonatal (NF-P3/80--third passage, 80% confluence) and adult (AF-P1/80--first passage, 80% confluence) rat cardiac fibroblasts were exposed to cyclic stretch (biaxial, 1 Hz), which enhanced FAK phosphorylation at Tyr397. Proliferation (anti-5-bromo-2'-deoxyuridine and anti-Ki67 nuclear labelling), differentiation into myofibroblasts (expression of alpha-smooth muscle actin--alpha-SMA), and the activity of matrix metalloproteinase-2 were equally enhanced in stretched NF-P3/80 and AF-P1/80. Treatment with the integrin inhibitor RGD peptide impaired FAK phosphorylation and increased apoptosis (TUNEL) in non-stretched and stretched NF-P3/80, whereas FAK silencing induced by small interfering RNA modestly enhanced apoptosis only in stretched cells. RGD peptide or FAK silencing suppressed the activation of NF-P3/80 invoked by cyclic stretch. In addition, NF-P3/80 depleted of FAK were defective in AKT Ser473, TSC-2 Thr1462, and S6 kinase Thr389 phosphorylation induced by cyclic stretch. The activation of NF-P3/80 invoked by cyclic stretch was prevented by pre-treatment with the mammalian target of rapamycin (mTOR) inhibitor rapamycin, whereas supplementation with the amino acid, leucine, activated S6K and rescued the stretch-induced activation of NF-P3/80 depleted of FAK.
These findings demonstrate a critical role for the mTOR complex, downstream from FAK, in mediating the activation of cardiac fibroblasts in response to mechanical stress.
The cardiac fibroblast is the most abundant cell type present in the myocardium and is mainly responsible for the deposition of extracellular matrix (ECM). Important components of cardiac ECM include structural and adhesive proteins such as collagen and fibronectin. Excess deposition of cardiac ECM (fibrosis) has been associated with the pathophysiological mechanical overload of the heart. Therefore, the role of cardiac fibroblasts in "sensing", "integrating" and "responding" to mechanical stimuli is of great interest. The development of in vitro strain apparatuses has allowed scientists to investigate the effects of mechanical stimuli on cardiac fibroblast function. Cardiac fibroblasts express ECM receptors (integrins) which couple mechanical stimuli to functional responses. Mechanical stimulation of cardiac fibroblasts has been shown to result in activation of various signal transduction pathways. The application of defined mechanical stimuli to cultured cardiac fibroblasts has been associated with ECM gene expression, growth factor production, release and/or bioactivity as well as collagenase activity. Ultimately, for fibrosis to develop the overproduction of ECM must overcome any associated increases in collagenase activity. Mechanically induced upregulation of ECM production may follow direct or indirect pathways through the autocrine or paracrine action of growth factors. Given the complex nature of the interstitial milieu of the working heart, additional research is needed to further our understanding of the roles that mechanical stimuli play in excess deposition of myocardial ECM.