Alves-Pereira et al. Vibroacoustic Disease, Response of Biological Tissue to Low Frequency Noise
Mariana Alves-Pereira, Joao Joanaz de Melo, Maria Cristina Marques, Nuno A.A. Castelo Branco
11th International Meeting on Low Frequency Noise & Vibration and Its Control, Maastricht The Netherlands, 30 Augus to 1 September 20o4
BACKGROUND: Vibroacoustic disease (VAD) is a systemic pathology caused by excessive exposure to low frequency noise (LFN). Until 1987, it was thought that the pathological effects of excessive LFN exposure were limited to the realm of cognitive and neurological disturbances. After the autopsy findings in a deceased VAD patient, it became clear that LFN impinges on the entire body, particularly the cardio-respiratory systems. In 1992, rodents were exposed to LFN, and the respiratory tract was studied through scanning and transmission electron microscopy. Pericardial, tracheal and lung fragments, removed with informed consent from VAD patients, have also been studied with light and electron microscopy. This report summarizes what is known to date on the tissue and cellular response to LFN exposure.
- TUBULIN-BASED STRUCTURES: Cilia are tubulin-based and exist in normal pericardia as well as in the respiratory tract. In VAD patients, pericardial cilia cease to exist, while tracheal and bronchial cilia are distributed in abnormal arrangements. In LFN-exposed rodents, respiratory tract cilia appear sheared, clipped or shaggy.
- ACTIN-BASED STRUCTURES: Cochlear cilia are actin-based structures, as are brush-cell microvilli that protrude into the respiratory tract airway. In LFN-exposed rodents, both structures appear fused. Actin filaments are also a fundamental element of the cellular cytoskeleton. In VAD patients’ pericardia, cytoskeletal deformations may be a consequence of LFN-induced changes of the actin filaments.
- BIOTENSEGRITY HYPOTHESIS: One of the most consistent findings in almost all human and rodent tissue fragments is the abnormal proliferation of collagen and elastin. It is hypothesized that the principles of biotensegrity structures may contribute to the explanation of tissue and cellular responses to LFN exposure.
For the past 24 years, the effects of low frequency noise (LFN) (<500 Hz, including infrasound) exposure have been the object of intense scientific inquiry. Vibroacoustic disease (VAD) is a whole-body pathology caused by excessive exposure to LFN, either due to occupational sources or environmental sources. The response of biological tissue to LFN has drawn great interest, particularly given the significant structural, or morphological, changes of the exposed organs, tissues and cells.
In 1987, an autopsy was performed on a deceased VAD patient, as specifically bequeathed by the patient in his will. Until then, it was thought that LFN-induced pathology was restricted to the realm of neuropathophysiology. Autopsy findings disclosed, among several other extraordinary features, widespread thickening of blood vessel walls, and abnormally thickened cardiac structures, namely valves and pericardium. Fibrosis (collagen proliferation) was also identified in the lungs.
In 1992, Wistar rats began to be used as animal models for VAD. Rodents were exposed to LFN, and fragments of different sections of the respiratory tract were studied with electron microscopy. In 1996, the first pericardial fragments were taken from fully informed VAD patients who were undergoing cardiac surgery (for other reasons). Since then, 12 VAD patients have provided pericardial fragments for our study. Similarly, several other VAD patients have provided fragments of respiratory tract tissue (epithelia) through biopsy (conducted for other reasons). All these tissue samples were examined with electron microscopy.
The goal of this report is to contribute to the characterisation of the biomechanical response of tissue to the presence of excessive LFN, drawing upon the data collected from the microscopy studies. …
LFN induces tissue reorganization and neo-formation. One of the underlying purposes may be the need to maintain structural integrity in a viscoelastic environment undergoing LFN-induced vibratory propagation.
Actin-based structures seem to have a tendency to fuse. Indeed, microvilli fusion (as seen in the brush cell) will alter the kinetic properties of the structure. Cochlear cilia, for example, are supposed to vibrate freely against the upper tectorial membrane, when an acoustical pressure wave is transduced along the basal membrane. This movement is what relays the acoustical signal to the brain. However, in LFN-exposed rats, cilia are fused together, as well as with the upper tectorial membrane. Hence, when the basal membrane attempts to transduce the acoustical signal, instead of freely vibrating, cochlear cilia, now a non-vibrating structure, will be pulled. If something similar occurs in the cochlear cilia of LFN-exposed humans, then perhaps discomfort might be felt. Discomfort that may be closely associated with the concept of annoyance.
The destruction of ciliary fields is dramatic, and might be related to its structural specificities. The cilium is anchored to the cellular cortex through an actin-based network located within the cytoskeleton directly under the plasma membrane. Given the response of other actin-based structures, namely brush cell microvilli as well as cochlear stereocilia, it is not unreasonable to hypothesize that perhaps the actin filaments that compose the cytoskeleton might also be reacting to LFN exposure. Corroborating this notion are transmission electron microscopy images showing intact internal ciliary structures. Yet, strands of apparently sheared cilia appear lying horizontally on the epithelial surface, and ciliary fields are depleted.
The response of the pericardium to LFN certainly appears to be an adaptation response. This does not exclude the loss of functional capabilities, for example, not a single cilium was found in mesothelial cells. Despite the dramatic alterations of the pericardia, heart function is normal and no diastolic dysfunction exists in VAD patients. It would seem that this newly formed loose tissue layer, rich in vessels and adipose tissue, with numerous elastic components, plays a very important role, possibly of a pneumatic and logistic nature, in maintaining normal function of the heart in these patients.
The ruptured cellular membranes seen in the pericardial mesothelial layer are very unusual. Cellular debris is seen in all layers of the pericardium. This sort of cellular death is not related to the normal, programmed, or apoptotic, cellular death. In VAD patients’ pericardia, cellular death seems to be associated with mechanical processes and stresses. The fact that the cellular debris is being spewed into the pericardial sac may be a contributing factor to the development of auto-immune diseases in VAD patients.
It would seem that in the presence of LFN, living tissue responds by reinforcing its structural integrity. This is strongly suggested by the thickening observed in blood vessel walls, as well as in alveoli walls.
In conclusion, while biochemical and molecular signalling play fundamental roles in tissue re-organization, given the nature of the mechanical insult perpetrated by LFN, mechanically-induced signalling must also be greatly implicated.
Mariana Alves-Pereira João Joanaz de Melo New University of Lisbon, DCEA-FCT, Caparica (mariana.pereira/oninet.pt) Maria Cristina Marques Dept. Physiology, School of Pharmacology, University of Lisbon, Portugal Nuno A. A. Castelo Branco Center for Human Performance, Alverca, Portugal (n.cbranco/netcabo.pt)