The flat endothelial cells line all the mammal’s vessels (including lymph vessels) as its largest organ. Responsible for the entire transport of energy- and substrate metabolism as well as for many vital functions, they have a very large surface area (approx. six football fields in adults) [1] . The endothelial cell corresponds in its structure to a somatic cell and is specified for its diverse tasks, whereby the respective vessel (capillary vessel, artery) as well as the type of tissue (splanchnic area, kidney, brain) is responsible for its further specification [2] . It differs in shape, expression and surface as well as its staffing of receptors of the adrenergic system. According to their ultrastructure, endothelial cells are differentiated, depending on their organ-specific substructure, into various types of continuously, fenestrated and discontinuous endothelium. The circulatory system is self-contained in a combination of vessels, connected in series and in parallel, in which, in accordance with Ohm’s law, the total resistance decreases with each additional parallel connection [2] . By regulating the resistance via the upstream arterioles, we physiologically find laminar flows with uniform velocity, strictly bound to the vessel size, in the capillary network. This is a crucial precondition for the diverse and vital tasks of the microcirculation [2] [3] . In contrast, we find chronic oscillatory stress, a strong causal factor for atherosclerosis, at vascular branches and stronger curves of medium and larger vessels. One of the main tasks of microcirculation is to adapt vascular blood flow to current needs [1] [4] . The functional vessel density (FVD) in resting muscle is about 25% of the total vessel density (TVD). Conversely, this also means that blood flow can be increased by a multiple [5] . The compensatory capacity of the capillary network is thus many times higher than that of the “macrocirculation”. Under physical strain, a so-called capillary recruitment according Moore and Fraser 2015 [6] , begins by lowering the vascular resistance of upstream arterioles, resulting in a significant increase in the nutrient exchange surface and a decrease in the distance between two capillaries with a consequently reduced diffusion distance for oxygen and nutrients. The regulation of local blood flow (so-called vasomotor function) is extremely complex and “orchestrated” [4] . It is controlled by intrinsic and extrinsic factors (e.g., autonomic nerve system and vasoactive hormones, e.g., adrenaline, vasopressin, angiotensin, serotonin) which modulate intrinsic activity [1] , dependent also on vessel size and the distribution of adrenergic receptors to a given organ.

One basis for intrinsic regulation is formed by the Bayliss effect [7] . Blood flow is kept constant: If blood flow increases, vasoconstriction occurs, if blood flow falls, vasodilation occurs. A second basis is metabolite factors according to the classical theory, in which local hypoxia leads to an increased release of vasodilatory active substances (e.g., NO, ATP, prostaglandins), causing an increase in local blood flow. Accumulating metabolites such as lactate, hydrogen ions, potassium and adenosine maintain this effect [1] . One of the most important and mainly responsible prerequisites for the NO bioavailability is the classical laminar shear stress response due to mechanical forces according Chien 2007 [8] . NO is triggered in the classical way by blood flow causing a mechanical change at the endothelial cell membrane and formed from its precursor L-arginine via NO-synthetase (NOS). NO mediates vascular relaxation by activation of the soluble guanylyl cyclase (sGC) which catalyses the conversion of guanosine triphosphate (GTP) into 3’-5’-cyclic guanosine monophosphate (cGMP).

The latter is extraordinarily typical for the microcirculation, but one of the least explained phenomena: vasomotion.

Vasomotion was first observed in the classical example of a bat vein and described as a rhythmic contractility that accelerates blood flow forward via fine and synchronised pulsations [9] . The causes and control of which have not yet been fully elucidated. Current state of knowledge is that vasomotion depends on the integrity of the endothelium and apparently serve to optimise the nutrient support [10] . Vasomotion can be directly observed in vivo in SDF-video microscopy. Quote from Aalkjaer C. Mulvany MJ 2020) [10] in cap. 1.3 page 7: “Perhaps the only feature related to vasomotion which is agreed by everybody is that an oscillation of the smooth muscle cell membrane potential is the background for the oscillation of the individual smooth muscle cell tone and also for the synchronization of the smooth muscle cells […] This strongly suggests that [Ca²⁺] in the smooth muscle cells is also oscillating in a synchronized manner—and this is indeed the case. […]”. There is deeper insight in the original article [10] .

The extent of endothelial involvement in clinical syndromes is immense, as are the potential factors that can influence microcirculation in both positive and negative ways. The most important potential influences arise from vital functions such as oxygen and nutrition supply, growth, embryogenesis, blood coagulation, immune regulation, etc. The main causes of dysfunction are those that can disrupt the integrity of the endothelium, in particular an excess of oxidative and oscillatory stress.

Crucial for both, a synchronised blood flow regulation and the maintenance of vascular health, is the adequate release of NO with the right amount, right quantity, at the right place and to the right time [11] . As strong antioxidant, it plays a decisive role in the homeostasis of the entire redox metabolism with interruption of lipid peroxidation and therefore decrease of aggressive free oxygen radicals (ROS) ( [11] [12] Table 1). As free radical (in a gaseous state), it can diffuse freely through the membranes. The vascular effects of NO are presented as vascular protective, regulatory or as deleterious [11] [13] . How the reaction really turns out, depends according to Laurindo F. et al. [11] on several factors. According to these authors, the unfavourable properties usually are associated with an excessive NO production, the protective NO effects are attributed to a steady and for the specific situation adequate NO production. Not only NO, but also its three isoenzymes of endothelial NO-Synthetase are involved in redox signalling pathways. Depending the kind of isoenzyme and surrounding conditions, they have likewise either protective effects or such that are deleterious as shown in Table 1.

As a result, the dependence of an adequate NO-provision on physical forces leads to a sensivity to external stressors that would be capable of leading to irregular mechano-transduction, possibly leading to an increased and inadequate NO supply. More details to the whole theme in articles from [11] [12] [13] [14] .

After Original source [13] FIG 1 in WINK AA. MITCHELL J (1998) CHEMICAL BIOLOGY OF NITRIC OXIDE: INSIGHTS INTO REGULATORY, CYTOTOXIC, AND CYTOPROTECTIVE MECHANISMS OF NITRIC OXIDE, Radiation Biology Branch, National Cancer Institute, Bethesda, MD, USA from Book Free Radical Biology & Medicine, Vol. 25, Nos. 4/5, pp. 434-456, 1998. Published by Elsevier Science Inc. 0891-5849/98 $0.00 1.00 reference FIG 1 Page 435.

In the area of the microcirculation, further vasodilating substances play a decisive role. Vascular segments in arterioles respond to endothelial autacoids such as angiotensin, serotonin, eicosanoids [2] and to agonists such as acetylcholine, bradykinin, or substance P as well as to transmural pressure changes. They do this not as isolated entities, but in a coordinated manner. This is attributed to the Endothelium-derived-hyperpolarising-factor (EDHF) [11] . EDHF has a long-distance effect, as its locally triggered formation can also trigger a rectified vascular response up- and downstream. The calcium-dependent activation of potassium efflux by EDHF is followed by hyperpolarisation with transmission of electron transfer within the vessel wall via the gap junctions and without loss of time [15] . The transmission reaction is comparable to a school of fish, very fast and synchronised [5] . The possibilities of microtactile stimulation compared to triggering via acetylcholine, were experimentally tested and confirmed [5] .

All sequential series of reactions here depend on the integrity of the endothelium and involve the endothelial cytoskeleton. Since it is a vital endothelial function, the complex process of inflammation can be disrupted at any level according to Suthahar [16] . In line with its high relevance to the topic of our work, we present a more detailed description to show how sensible the whole process, e.g., for mechanic stress, is: An inflammatory response is essential as a physiological defence mechanism against, e.g., bacteria, viruses, injuries. Point of no return is the diapedesis of leucocytes. The further course leads in the favourable case to a restitutio ad integrum, in the unfavourable to a chronic inflammation with fibrosis, defect healing and possible organ damage.

Important works on the state of the science come from Ley et al. (2007) [17] and Serhan et al. (2007) [18] , related work in particular from Nussbaum and Sperando (2011) [19] and [1] [20] . According to Ley [17] , the orderly process in all phases is crucial for its outcome. Here is presented the undisturbed course:

The circulating leukocytes move passively in the blood stream. In the postcapillary venules, local changes near sites of inflammation in the hemodynamics lead to a reduced blood flow rate. This increases the likelihood of leukocytes coming into contact with endothelia. The endothelium is in an activated state for a few hours and expresses adhesion molecules that lead to leukocyte binding. The “slow rolling” of leukocytes is also made possible by another inducible endothelial E-Selectin, which is based on a partial activation of Integrins on the leukocytes [17] (compare Figure 1). The actin cytoskeleton is as well actively involved in this process. Further chemokines, partly from the endothelium and partly from the extracellular space (ECR), activate tight binding and then amoeboid passage of leukocytes into the ECR. Selective changes in permeability (gate-keeper-function of the endothelial cell) allow cellular components such as neutrophils and monocytes, to move from the intravascular space to the ECR. More details to the sequences in leucocytes diapedesis are presented in standard works [1] [19] . There is an intensive interplay between endothelial secreted mediators

(cytokines) and such of the ECR [1] [16] . Anti-inflammatory signals such as corticosterone mitigate the severity and limit the duration of the early phase [16] .

In summary, the process of inflammation is a complex interplay between a temporally and spatially defined process of mutual influence and activation between factors of the intra- and extra-vascular space. At the centre of the process is the adequate gate-keeper-function of an endothelium in an integrity state. After diapedesis of the leucocytes, an orderly process depends on the absence of increased oscillatory and oxidative stress, in order to lead to a restitutio ad integrum. In the other case, defect healing can occur due to a shift of the equilibrium in the direction to chronic inflammation and fibrosis. In the clinical medicine shifts to a chronic inflammation and the prevention of themselves play a big role [15] .

The standard works by Buckley et al. (2014) [21] and Serhan et al. (2007) [18] describe the sequences after the leukocyte diapedesis: Appropriate “checkpoints” and “stop signals” prevent further leukocyte entry. Lipoxins, resolvins and prostaglandins act in an active pro-resolving process. This paves the way for the migration and differentiation of monocytes to phagocytosis, for the chemokine gradient normalisation (which allows the leukocytes to undergo apoptosis) and for exiting the tissue via the draining lymphatic vessels. Failure of such regulatory mechanisms can lead to a state of chronic inflammation, causing continuous tissue damage and progressive fibrosis. A classic example is the chronic heart failure by “remodelling” of heart [16] .

At heart, immunocompetent myofibroblasts and factors of the ECR actively modulate the development of initially perivascular and later progressive fibrosis. Starting points can be the development of myocarditis into a chronic form, state after myocardial infarction and/or chronic mechanic pressure load on the heart (systemic high pressure or pulmonary hypertension). The consequence is the increase in diffusion distance, the decrease in capillary density, an impaired electroconductive system with cardiac arrhythmia, disruption of angiogenesis, leading again to a deteriorated substrate and oxygen supply with a self-reinforcing process: a vicious circle [16] .

Physiologically physical forces constantly act on the organism, e.g., gravidity, pressure, shear stress, vibration. The major ones are tangential forces (e.g., laminar shear stress) or stretching forces (e.g., pulsatile distention) from the blood according to Fernandes, C.D. et al. (2018) [3] and Mazzag et al. (2014) [22] . As described above, internal oscillatory stressors are physiologically limited by the vessel size which is a critical factor in maintaining vital functions [3] . The regulation of several vital cellular processes via mechano-transduction and signalling networks including growth, differentiation, migration, angiogenesis and apoptosis, is essential [1] [3] . During morphogenesis shear stress directs the formation of the vascular tree according Hahn and Schwartz (2009) [23] . Changes in shear stress determine instantaneous vasomotor changes which are regulated on a “beat-to-beat” basis [3] in order to maintain a constant laminar stress and optimize the conductance artery flow distributive function. At the same time, it is important to rely on sufficient NO release [3] . An overview of the different effects of shear stress is given in Figure 2.

The viscoelastic structure of the endothelial “tensegrity”-structure offers the foundation for mechano-transduction of forces. The term “tensegrity” was coined by R. Buckminster Fuller (1975) [24] , architect of the geodesic dome, where discontinuous compression and continuous tension were used to achieve the highest possible stability combined with lightness. Additional anchorage points are used to transfer mechanical forces to the individual compression and tension elements [25] . The equivalents at the endothelial cell level are the three intercommunicating networks of protein filaments and their anchor points.

Actin filaments as the elastic part, serve to maintain the cell shape by forming a ring under the cell membrane [25] with a communication network to flow sensors (mechano-sensors) and membrane focal adhesion points (FAS)—the “anchor points in the tensegrity model”—as well as the intercellular gap junctions (CCAP) [25] . According to Dudek et al. [26] , over 80 actin-binding proteins are critical participants in the generation of tensile forces. The original article [25] provides a deeper insight into this complex topic. In response to contractile stimuli, actin- and myosin filaments form membrane-bound, parallel organised units, called “stress fibres” that stimulate the sliding of myosin along

the actin filaments. This leads to an increase in intracellular tension and thus cell contraction according Wang et al. (2009) [27] and Lee et al. (2003) [28] . The closing and opening of the paracellular gaps in response to inflammation, ischemia and invading substances (gate-keeper-function) is essential according to Patrick Belvitch et al. (2018) [29] . Actin filaments also make up the so-called microvilli. These contain a central bundle of actin filaments, also anchored to the cytoskeleton. Microvilli are found in various organs (e.g. intestine) where they have resorptive properties.

Microtubules constitute the compression element with pressure-resistant hollow rods, consisting of α- and β-tubulin [25] . They are connected to the ECR by integrins (transmembrane proteins) and support the cellular structure in communication with actin filaments and intermediate filaments as well as the formation of spindles for mitosis.

The observation that many processes obviously take place much faster than the mechano-chemical pathway via gene expression and protein synthesis would allow (namely minimum some seconds), led to an intensive research in the “tensegrity” structure and to the definition of the “biophysical pathway”. This relies on direct physical links between specific mechano-sensors of the endothelial surface and cytoskeleton elements. It allows cells to transfer mechanical stimuli over long distances and very important, a spatially heterogenic excitation to transform information in a desired reaction [27] . Crucial work with important relevance to our work, is the research on the dynamics and distribution of transmission in response to “noisy flow” from Bori Mazzag et al. 2010 [30] and Mazzag B, Gouget C, Hwan Y, Barakat AI 2014 [22] . By “noisy” flow, the authors mean an “oscillating or turbulent flow under conditions with random fluctuations in the flow properties of pressure and velocity”, Quote Mazzag, Barakat 2010 page 912 [30] .

Predecessors in the exploration of the “biophysical pathway” in the early 2000’s were Wang et al. [8] and Davies et al. (2005) [31] . Significant works have been contributed in this context by Helmke et al. [32] , Hsu, H. J., Lee, C.F, Locke, A. et al. (2010) [33] ; Hwang, Y., Gouget, C. L. M and Barakat, A. I. (2012) [34] .

To better understand the dynamics of force transmission via cytoskeletal filaments, a number of mathematical models have been developed. The authors Mazzag and Barakat present an overview (possibilities and limitations) in [22] .

The Temporal Network Model, as presented in (2010) [30] and (2014) [22] is based on a viscoelastic structure of a tensegrity model, in order to develop insight of “noisy” flow transmission and to define which transmission structures are sensible to “noisy” flow. This model is shown in Figure 3.

The results show that the amplitude of the oscillations in the “noisy” flow will be answered more strongly than its duration. Another significant implication is that FAS (Focal adhesion points - equal anchoring points to ECR), due to their high sensivity to noise, are prime candidates for acting as cellular “Noise detectors” [30] .

A summary assessment follows in Mazzag 2014 [22] with further developments of models, e.g., for the spatial distribution of mechanical forces during transmission such as the Spatial temporal network Model; according to the authors [22] , there were important contributions from the original articles from [34] and Mazzag and Barakat (2011) as well as Mazzag et al. (2003).

In summary, the results provide the strong frequency dependence of force transmission with definition of a threshold value for actin filaments (more sensible) and microtubules.

Another issue for the authors was the saturation behaviour when the signal persists and an explanation, as to why the natural frequencies, generated by organs of the organism itself, do not lead to a long propagation of transmission. We cite the authors Mazzag and Barakat 2014 p. 107 [22] :

“In the case of oscillatory forcing, the deformation-related stress as in the case of constant forcing, exhibits an initial transient before it eventually saturates to a time-periodic steady state response. Importantly the saturation amplitude of the deformation-related stress at the nucleus is found to be strongly dependent on the forcing frequency. Figures 3D and E illustrate the saturation amplitude of deformation-related stress at the nucleus as a function of forcing frequency for transverse and axial forcing, respectively. In both the axial and transverse directions, a low-frequency (<0.1 Hz) mechanical stimulus is transmitted to the nucleus without decay in its amplitude, whereas a high-frequency mechanical stimulus undergoes significant decay in amplitude. This implies that individual stress fibres act as low-pass filters of mechanical forcing. Interestingly, transverse motion exhibits a much broader filter width than axial motion: the filter width for transverse motion extends to f ~ 1000 Hz whereas the one for axial motion extends to only f ~ 1 Hz” […] (Remarks: citation italic letters).

Second important quote page 101 [22] :

“As already described, oscillatory flow has been reported to induce EC dysfunction and to correlate with the development of early atherosclerotic lesions. Therefore, we also investigated the response of the simple networks described in the previous paragraph to oscillatory flow. The results revealed that the peak deformation (defined as the largest deformation within a period after the asymptotic time-periodic behaviour is attained) of each of the structures in the network (mechano-sensor, actin stress fibres, microtubules and nucleus) is strongly frequency-dependent. At sufficiently low oscillatory frequencies, the peak deformations match those for constant forcing; however, above a threshold frequency, the peak deformations drop significantly. The analysis demonstrated that this threshold frequency is in the range of 10⁻⁵ - 10⁻⁴ Hz for microtubules and 10⁻³ - 10⁻² Hz for actin stress fibres, suggesting that stress fibres can effectively transmit force over a wider frequency range.” “[…].” [Remarks: Italic letters from me]

Experimental researches by Na et al. (2008) [35] were experimentally comparing the velocity of mechano-transduction via the bio-physical and via the mechano-chemical pathway (growth factor and gene expression). The authors used comparable physical exposures for Infrasound (0.3 Hz), duration 30 s, sound pressure 1.8 Pa (studies with 1.8 Pa up to about 20 Pa). The most important results were the confirmation that the speed was 40 times faster than by mechanical-chemical means (confirming the above results), namely 300 ms (milliseconds). Beyond this, the findings were that the “Stress-Induced Src Activation depends on Integrin Activation, Substrate Stiffness, Prestress and F-Actin Integrity” [35] , quote from Na et al. page 1. Remarks: in italic letters (from me) [35] .

According to [3] the cytoskeleton itself is a mechano-sensor. On the side facing the vessel (luminal), mechano-sensors are especially the glycocalyx, integrins, cell-cell junctions (CCAP), caveolae, lipid rafts, G-protein coupled receptors and ion channels. They are activated according to their location via shear stress [3] (Figure 4). According to the author [3] , endothelial mechano-sensors are altered in their microenvironment by shear stress and can activate intracellular signalling pathways in this new formation. The fluidity of microdomains in the plasma membrane is altered [3] . This leads according to [3] to a spatial rearrangement of various proteins and thus to the activation of signalling pathways. The transmission of forces takes place via the three intercommunicating networks of the cytoskeleton to the basal region of cytoskeleton (e.g., Integrins) [3] [22] [30] .

One of the most important mechano-sensors is the glycocalyx ( [1] [3] Figure 4). In critically ill patients the extent of the glycocalyx damage (so called shedding) correlates with the severity of disease and mortality [1] [36] [37] .

Like identified to date, mechano-sensors are presented in Figure 4 (status 2019).

Additional recently defined endothelial mechano-sensors, the PIEZO-1 channels, have been clearly established as a sensory system of internal organs by the receptors for pressure and vibration in all vessels. Due to the great importance of their breakdown, Ardem Patapoutian received the Nobel Prize in Medicine 2021. According to Rode et al. (2017) [38] , Piezo-1 is responsible for flow-sensitive, non-inactivating, non-selective cationic channels which depolarize the membrane potential: Ca²⁺ permeable Piezo-1 channels are activated by physical force on the cell membrane (compare Figure 5). PIEZO-1 sense whole body’s physical activity to reset cardiovascular homeostasis and enhance performance. They are critical for lymphogenesis and homeostasis and are important shear stress mechano-sensors [39] . PIEZO-channels are crucial in all multicellular organisms, i.e., also invertebrates such as flies and vertebrates (fish) [40] . A schematic representation of an embedded PIEZO-1 channel is shown in Figure 5.

The existing epidemiological studies almost exclusively consider the audio-vestibular organ, respectively the involvement of individual brain structures [49] , as organs, possibly affected by exposure to noise in low-frequency ranges. In comparison with electromagnetic fields, everybody accepts that impacts on organism are not depending on a perception. Why not here? This question has already been asked in 2007 [50] . Many health disorders or manifest clinical symptoms cannot be explained with purely audio-vestibular impact. Since around 2015, the author noticed many complaints worldwide by the residential situation. They are corresponding to functional microcirculatory disorders according to a reduced and uncoordinated NO-bioavailability.

These are, e.g., dizziness, school performance disorder, fatigue, tinnitus, muscular weakness and headaches as signs of a disturbed and inadequate support with nutrients and O₂. With chronic exposure, symptoms occur such as increased blood pressure, cardiac arrhythmia, breathing disorders, immune deficiencies, late-onset epilepsy [50] . In a second step a working hypothesis was developed that tested the prerequisites for a direct stressor effect on both, the endothelial cell level and the technical side. The results, available to date from epidemiological studies, experimental and animal experimental studies, were included in the considerations.

In a third step the currently available literature on molecular endothelial physiology and pathophysiology was reviewed with regard to the possibility of mechano-transmission of mechanic forces if outgoing from an extern acting stressor. The identification of PIEZO-1-channels 2021 as important mechano-sensors for sound and vibration strengthened the evidence for our hypothesis. Extensive literature on pathohistological findings in occupational exposure to infrasound from the 1980s [50] , later from the 2000s on exposure of residents to wind turbines [51] and the reassessment of these findings were included.

Due to the audio-acoustic approach, the changed conditions for sound propagation in the viscoelastic organism did not have been considered in the past. We do now. For the same reason, it makes the so-called perception threshold irrelevant as this only refers to audible sound and air transmission.

➢ Noise is a mechanical force, therefore subject to physical laws;

➢ The existence of numerous mechano-sensors for sound and vibration at the membrane/endothelial level with newly identified, in particular endothelial PIEZO-1-channels, is state of the science;

➢ Mechano-transduction of mechanical forces is crucial for many vital vascular regulations;

➢ The mechanical transmission of forces via the structures of the endothelial cytoskeleton is state of the science;

➢ Proven microtactile excitability of endothelial cells with rapidly propagated conduction up- and downstream.

➢ Noise, when it affects organisms, is under certain conditions in frequency, sound pressure, effect/time profile, duration, able to change the physiological laminar flow situation in the capillary bed in the sense of an oscillatory environment. In this case, the transition of mechanical forces might take place in an uncontrolled manner;

➢ In consequence vasomotor functions and in particular vasomotion could be disturbed;

➢ The expected effects of chronic impact could lead to a chronic inadequate nutrient supply and therefore to a shift of equilibria to disequilibria, especially for the redox systems and for the responses to inflammation processes.

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] . Empiric data’s in experimental studies show clear indications that exposure to IFLN leads to an ROS-increase [56] . Positive evidence also indicates the study of Chaban et al. [57] and very noteworthy, the direct cell effect is shown in Effect of infrasound on the growth of colorectal carcinoma in mouse [58] . In clinical medicine, there are currently considerations about the possible benefits of infrasound in the therapy of human colon carcinoma. High evidence for a direct cell and membrane effect are the results of the review of Roos, W and Vahl, CF (2021) [45] which focus on the evidence for interaction of cellular structures, resp. sensible membrane structures, in a stress reaction. A possible disturbance of microcirculation is discussed. A positive evaluation in this direction is also the metanalysis Dumbrille, A et al. (2021) [59] : This evaluation results in the causality of adverse health effects (ADH’s) and the stressor in all “Bradford Hill criteria”. Reported were adverse effects on animals which revealed not only stress reactions but also negative effects on fertility, development and reproduction [60] . With regard to the Bradford-Hill criterion dose response, analyses showed a demonstrable deterioration in mental performance from residents, living within 1.4 km of wind turbine(s) to those living outside this radius [61] . Increased complaints raised when the frequencies approach deeper ones (in the mentioned example 0.2 Hz) [62] .

Positive evidence for the frequent occurrence of atrial fibrillation is presented in the “nurse cohort study” [63] . My statement here: The development of atrial fibrillation in the absence of hypoxemia corresponds with structural changes and therefore conditions for disturbances of the electromechanics.

Research [50] on the symptomatology of occupationally with IFLN confronted groups in the 1980s showed wall thickening of vessels. According to the authors animal studies showed abnormal amount of fibrosis/collagen in trachea, lungs and pleura; damaged (sheared) tracheal and bronchial cilia; fused actin-based microvilli of tracheal and bronchial brush cells. Thickening of the pericardial wall has been observed in occupationally exposed persons to ILFN [50] and in persons living in the vicinity of large IWT plants [51] as a specific alteration. Figure 7 shows pericardial wall thickening in chronic occupationally exposed persons in the eighties (so called Vibroacoustic Syndrome “VAD-syndrome”) in comparison to non-exposed.

Figure 8 is the presentation of a non-exposed bronchial epithelium of a rat in comparison to an exposed one in Figure 9. The figures are showing the changes in the microvilli (actin) before and after exposure. The interpretation of these findings suggests a shift in the homeostasis of the redox system towards chronic inflammation and fibrosis.

The choice of sound pressure levels (SPL) in dB in experimental studies, is often higher than expected from IWT’s installations.

Objection:

a) The SPL in dB(A) can only map airborne noise in the frequency part of hearing ( compare cap. 2).

b) The effect of the steady drip when living nearby emissions must be considered as strong factor [64] , the exposure time in reality often can be (also for sensitive groups) 24/7 hours/a day. In contrast, the time in animal experimental studies is limited for practical reasons. Similar applies to the higher sound pressures in the context of occupational exposure: Here, the times of exposure are limited; sensitive groups have no access.

However, the decisive factor is that the frequency of Noise was not recognised in its significance (e.g., use of 8 Hz in Chaban et al. [57] ). Added to this: The behaviour of sound propagation in the viscoelastic organisms differs in that way, that a decodable information about the lowpass filters becomes conceivable (compare cap. 2) [22] [30] [35] .

Exemplum Poulsen-Study [65] : As result, he found no statistically significant association between exposure to infrasound and the incidence for cardiovascular diseases. A relativization of the study took place by the author himself (e.g., study on relatively little IWT’s).

Important parts of the statements from Mazzag and Barakat 2010 [30] and 2014 Mazzag et al. [22] are based on computational models. As already mentioned, the authors themselves refer to possible limitations and results.

Quote from authors [22] Page 96: “Therefore, it is essential for models to be validated to the extent possible against experimental data. It is only after such validation is performed that mathematical models can potentially fulfil their promise of providing powerful and predictive tools for studying the dynamics and spatiotemporal organization of mechanically-induced responses in cells”.

My statement: Several predecessors [27] [33] [34] [35] have done essential preparatory work over years with high evidence; the whole process of mechano-transmission is highly dynamic with numerous pathways interlocking. Computational models are necessary to achieve the best possible approximation of dynamic processes to improve understanding of cellular mechano-transduction. The further work from Na (2008) [35] as an experimental study is one of the required experimental studies, which confirms the mathematical models. Studies in this direction have not taken place on infrasound emitting technical sources.

The influence of the extrinsic part on vasomotor function via the autonomic nervous system is the variable part that strongly depends on the individual abilities to compensate for stress factors. It is an additional influencing factor that is probably the reason why people in the same environment do not react in the same way in their symptomatology. The following can be expected when comparing a short-term stressor load with a permanent one: After an individual period of time, the compensation possibilities of biological systems are exhausted.

For further confirmation, we propose an experimental design with a determined number of infrasound exposed probands in comparison to non-exposed subjects. The positive group is exposed to a defined infrasound stressor in frequency, sound pressure p in (Pa), time/effect profile (impulsiveness) and duration. The design is double-blinded, in on/off design under SDF-video-microscopy technique, examining the sensible vasomotion via oral mucosa. Corresponding animal experiments are conceivable with regard to the assessment of direct vasomotor changes under infrasound (e.g. in hamsters via the cheek). The indications of changes in animal behaviour as well as reproductive behaviour in vertebrates and non-vertebrates would be a meaningful addition and extension of further scientific clarification.

Vascular health is strictly combined with NO bioavailability. Of great importance for its maintaining, is the classification of possible damaging environmental factors. The particularly sensitive population groups must be the bench. Our hypothesis can help to define sensitive stages for mechano-transmission of deep frequencies of “Noise”.