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270 Schirato et al. | Journal of Clinical and Translational Research 2024; 10(5): 269-282
occurrence are likely to be associated, based on individual of decompression, is sufficient to increase the production
responses. of MPs carrying interleukin-1β [15], a cytokine involved in
The present study was designed to observe if different inflammatory responses. The mechanism behind MP formation
decompression techniques would result in significantly different has been linked to high inert gas pressure, which induces singlet
outcomes, measured through different physiological stress oxygen formation. This toxic free radical is generated through
indicators, even in the absence of decompression sickness a cycle involving actin S-nitrosylation, nitric oxide (NO)
symptoms. For decades, there has been an ongoing debate about synthase-2, and nicotinamide adenine dinucleotide phosphate
how ambient pressure reduction should be conducted in non- (NADPH) oxidase activation [16]. NADPH oxidase, activated
saturation dives [4], i.e., whether the reduction of the ambient by neutrophils, generates reactive oxygen species (ROS)
pressure should start earlier or later in the decompression phase. through its heme enzyme, myeloperoxidase (MPO) [17]. ROS
Dissolved gas models, based on John S. Haldane’s tables [1] production by activated granulocytes and potentially by other
and later developed by many others, were, over time, partially cells is part of an orchestrated physiological first response of the
replaced by decompression algorithms based on the control immune system to potential aggressors. Therefore, it is expected
of bubble formation and growth, including, among others, the that higher expressions of MPO are linked to the generation of
varying permeability model developed by Yount [5], causing ROS, leading to MP production.
the speed in ambient pressure reduction, to start earlier in the Another expected physiological alteration related to
decompression phase of the dive, i.e., requiring divers to start decompression is heart rate variability (HRV). Recently published
decompression stops deeper in the water column. studies reported changes in HRV after exposure to hyperbaric
Given the low overall incidence of decompression sickness, environments [18,19]. HRV is defined as the undirected changes
there are little scientific data available to support or reject any in the interval between successive normal-to-normal heartbeats
decompression algorithm. However, there is a widespread (triggered by the sinus node, excluding extrasystoles) [20],
belief that including deeper stops in decompression schedules which results from the balanced action of the sympathetic and
reduces the physiological stress during ascent and the risk of the parasympathetic branches of the autonomic nervous system
decompression sickness. Conversely, some studies suggest that (ANS) [20] as well as other non-neural sources of variation.
slower ascents are related to higher counts of bubbles upon HRV is commonly studied in the time and frequency
surfacing [6]. Nevertheless, whether these counts translate domains, and occasionally through the application of non-linear
to a higher probability of decompression sickness remains methods [20]. Different HRV indicators have been associated
debated [7]. In one of the largest studies comparing the with sympathetic or parasympathetic activity. For many
incidence of decompression sickness in bubble-based models years, it was believed that the low frequency (LF) bandwidth
versus dissolved gas-based models (derived from Haldane’s of the HRV spectrogram (a frequency domain indicator) was
work), the United States Navy Experimental Diving Unit [4] associated with sympathetic activity, while the high frequency
concluded that decompression schedules with deep stops had (HF) band was related to the parasympathetic branch of the
a higher incidence of decompression sickness than those with ANS [20]. In reality, the association between a given bandwidth
shallower decompression stops. and one specific branch of the ANS is not so well-defined, and
These findings could be attributed to the different there are probably other factors contributing to the process.
supersaturation observed in the tissues with slower gas kinetics HF is highly impacted by respiratory pattern [20], with a
upon surfacing [4]. During deeper decompression stops, these response time akin to the parasympathetic response time of the
tissues are not yet saturated and continue to absorb gas from sinoatrial node. The LF band is associated with blood pressure
the blood [8]. This opposes the purposes of these stops and may control loops, supporting an association with sympathetic
aggravate the stress caused by decompression [4]. activity [20]. However, experimental evidence indicates that
Besides the well-documented appearance of bubbles, both branches of the ANS play a role in both LF and HF power.
activation of the immune system and small particle (microparticles A reduction in HRV has been reported in several cardiological
[MPs] or microvesicles) formation have been suggested to play and non-cardiological diseases, ranging from diabetes to
an important role in decompression sickness [9-11]. Hence, renal failure [21]. A reduction in HRV, when analyzed in the
decompression sickness is not merely a physical or mechanical frequency domain, has also been associated with inflammatory
problem, but instead the result of a complex biochemical processes in multiple studies [21,22].
process. MPs, shed by different cells in a regulated manner Given the clear role of inflammatory processes and immune
and carrying various nuclear components of their originating responses in compression and subsequent decompression
cells, such as RNA and DNA, are involved in cell signaling processes, studying HRV in this context could provide
and communication [12]. Different studies have identified important insights into the underlying physiological processes
them as markers of inflammatory diseases [12], and variations and potential outcomes of hyperbaric exposure. As different
in their levels and their cells of origin have been linked to a decompression protocols alter the dynamics of gas absorption
range of diseases and inflammatory processes [13,14]. During and release by tissues and, consequently, the physiological
decompression, or probably even earlier, immune system stress sustained by divers, we hypothesized that profiles with
activation and oxidative stress occur. A recent study found that deep stops and those with shallow stops would result in distinct
exposure to high-pressure environments, even in the absence changes in HRV.

DOI: https://doi.org/10.36922/jctr.24.00021