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The lymphatic pathway for microbubbles

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Costantino Balestra at HE2B - Haute Ecole Bruxelles-Brabant
Costantino Balestra
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Diving and Hyperbaric Medicine Volume 44 No. 1 March 2014 3
Editorials
The sites for formation of microbubbles that are routinely
detected precordially by Doppler after a decompression are
still a matter of debate. Firstly, microbubbles could form on
the endothelial wall of capillaries, at specifi c nanometric
sites, but the release mechanism of such small emerging
entities remains puzzling. They might also be formed from
pre-existing gas nuclei present in the blood when favorable
local hydrodynamic/supersaturation conditions generate
microcavitation and tribonucleation phenomena. Finally,
tissues could represent large pools for microbubble formation
and amplifi cation. Nevertheless, it remains unexplained as
to what the potential driving pathways might be.1
Knowing that the permeability of most of the blood capillary
network is quite low, an alternative is proposed for such
transport. The lymphatic system, which drains the interstitial
fl uid to guarantee the fl uid balance of tissues, could allow
the transfer of micrometric elements, like stabilized
microbubbles formed in tissues, over long distances. These
might then be reinjected into the bloodstream via the right
lymphatic and thoracic ducts. The characteristics of this slow
transport, activated by the muscular pump, could explain the
detection of vascular gas emboli (VGE) over long periods.
This hypothesis may give credence to a relatively old
empirical fi nding of combat and commercial divers: that
one should drive the boat fast to the dive site, but not on the
way back, to reduce the risk of decompression sickness.
These stories fi nally interested researchers enough to take a
scientifi c look at why this happens. It was confi rmed that 30
minutes of whole-body vibration before a dive (30 min, 30
msw) had preventive effects on post-dive bubble formation.2
As there was no observed change in fl ow-mediated dilatation
after vibration, the authors concluded that a nitrogen
monoxide-mediated mechanism was not involved; rather, a
mechanical dislodgement or enhanced lymphatic elimination
of gas nuclei was hypothesized.
There are several possible explanations for this effect. Firstly,
the vibrational force transmission to the whole-body should
interact with the blood fl ow as well as the endothelium in
order to eliminate the gas nuclei. In addition, vibrations
may increase the blood friction forces on the endothelium
favoring the detachment of gas micronuclei from the vascular
wall. Vibrations should induce, by force transmission, a
modification of endothelial spatial conformation. This
modifi cation should be responsible for a higher exposition
of gas nuclei to the blood fl ow drag forces. Finally, the
increase of lymphatic circulation, induced by vibration,
would allow the elimination of a part of intercellular tissue
micronuclei (Figure1).3
In conclusion, the effectiveness of vibration on VGE
elimination might be explained by the mechanical action
of vibration on the endovascular and tissue localization
of micronuclei. Other preconditioning situations showing
positive effects on the number of post-dive vascular gas
emboli also can be explained by increased lymphatic activity.
References
1 Hugon J, Barthelemy L, Rostain JC, Gardette B. The pathway
to drive decompression microbubbles from the tissues to the
blood and the lymphatic system as a part of this transfer.
Undersea Hyperb Med. 2009;36:223-36.
2 Germonpré P, Pontier JM, Gempp E, Blatteau JE, Deneweth S,
Lafère P, et al. Pre-dive vibration effect on bubble formation
after a 30-m dive requiring a decompression stop. Aviat Space
Environ Med. 2009;80:1044-8.
3 Leduc A, Lievens P, Dewald J. The infl uence of multidirectional
vibrations on wound healing and on regeneration of blood- and
lymph vessels. Lymphology. 1981;14:179-85.
Costantino Balestra, PhD
President, EUBS
Professor of Integrative Physiology, Haute Ecole Paul Henri-
Spaak, Brussels
E-mail: <costantino.balestra@eubs.org>
Key words
Doppler, bubbles, venous gas embolism, physiology
Figure 1
Accelerated peripheral elimination of radioactive tracer
during vibration (n = 5); Tc99-labelled albumin was injected
subcutaneously into the fi rst dorsal interosseous space; the gamma
camera was positioned over the axilla and the arm vibrated at 30Hz
using a physiotherapeutic vibrator.
The lymphatic pathway for
microbubbles
Costantino Balestra
... In divers, our mathematical derivation of the SMB stability considers the venous side of a tissue. However, it is admitted that SMB could form as well in the lymphatic vessels (Hugon et al., 2009;Balestra, 2014b) or the distal arterial tree (Arieli and Marmur, 2017). ...
Static Metabolic Bubbles as Precursors of Vascular Gas Emboli During Divers’ Decompression: A Hypothesis Explaining Bubbling Variability
Article
Full-text available
  • Jul 2019
Introduction: The risk for decompression sickness (DCS) after hyperbaric exposures (such as SCUBA diving) has been linked to the presence and quantity of vascular gas emboli (VGE) after surfacing from the dive. These VGE can be semi-quantified by ultrasound Doppler and quantified via precordial echocardiography. However, for an identical dive, VGE monitoring of divers shows variations related to individual susceptibility, and, for a same diver, dive-to-dive variations which may be influenced by pre-dive pre-conditioning. These variations are not explained by currently used algorithms. In this paper, we present a new hypothesis: individual metabolic processes, through the oxygen window (OW) or Inherent Unsaturation of tissues, modulate the presence and volume of static metabolic bubbles (SMB) that in turn act as precursors of circulating VGE after a dive. Methods: We derive a coherent system of assumptions to describe static gas bubbles, located on the vessel endothelium at hydrophobic sites, that would be activated during decompression and become the source of VGE. We first refer to the OW and show that it creates a local tissue unsaturation that can generate and stabilize static gas phases in the diver at the surface. We then use Non-extensive thermodynamics to derive an equilibrium equation that avoids any geometrical description. The final equation links the SMB volume directly to the metabolism. Results and discussion: Our model introduces a stable population of small gas pockets of an intermediate size between the nanobubbles nucleating on the active sites and the VGE detected in the venous blood. The resulting equation, when checked against our own previously published data and the relevant scientific literature, supports both individual variation and the induced differences observed in pre-conditioning experiments. It also explains the variability in VGE counts based on age, fitness, type and frequency of physical activities. Finally, it fits into the general scheme of the arterial bubble assumption for the description of the DCS risk. Conclusion: Metabolism characterization of the pre-dive SMB population opens new possibilities for decompression algorithms by considering the diver's individual susceptibility and recent history (life style, exercise) to predict the level of VGE during and after decompression.
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... Considering the involvement of many biological and physiological parameters such as endothelial function (Theunissen et al., 2013(Theunissen et al., , 2015, hydration (Gempp et al., 2009), vascular and lymphatic response (Hugon et al., 2009;Balestra, 2014), to mention only a few of the more recently studied variables, we believe that more research efforts are now necessary to further clarify these aspects of the complex pathophysiology of decompression. ...
Dive Risk Factors, Gas Bubble Formation, and Decompression Illness in Recreational SCUBA Diving: Analysis of DAN Europe DSL Data Base
Article
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  • Sep 2017
Introduction: The popularity of SCUBA diving is steadily increasing together with the number of dives and correlated diseases per year. The rules that govern correct decompression procedures are considered well known even if the majority of Decompression Sickness (DCS) cases are considered unexpected confirming a bias in the “mathematical ability” to predict DCS by the current algorithms. Furthermore, little is still known about diving risk factors and any individual predisposition to DCS. This study provides an in-depth epidemiological analysis of the diving community, to include additional risk factors correlated with the development of circulating bubbles and DCS. Materials and Methods: An originally developed database (DAN DB) including specific questionnaires for data collection allowed the statistical analysis of 39,099 electronically recorded open circuit dives made by 2,629 European divers (2,189 males 83.3%, 440 females 16.7%) over 5 years. The same dive parameters and risk factors were investigated also in 970 out of the 39,099 collected dives investigated for bubble formation, by 1-min precordial Doppler, and in 320 sea-level dives followed by DCS symptoms. Results: Mean depth and GF high of all the recorded dives were 27.1 m, and 0.66, respectively; the average ascent speed was lower than the currently recommended “safe” one (9–10 m/min). We found statistically significant relationships between higher bubble grades and BMI, fat mass, age, and diving exposure. Regarding incidence of DCS, we identified additional non-bubble related risk factors, which appear significantly related to a higher DCS incidence, namely: gender, strong current, heavy exercise, and workload during diving. We found that the majority of the recorded DCS cases were not predicted by the adopted decompression algorithm and would have therefore been defined as “undeserved.” Conclusion: The DAN DB analysis shows that most dives were made in a “safe zone,” even if data show an evident “gray area” in the “mathematical” ability to predict DCS by the current algorithms. Some other risk factors seem to influence the possibility to develop DCS, irrespective of their effect on bubble formation, thus suggesting the existence of some factors influencing or enhancing the effects of bubbles.
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... Indeed, vibrations could induce, by force transmission, a modification of endothelial spatial conformation. Secondly, the increase in lymphatic circulation induced by vibration (Leduc et al., 1981;Balestra, 2014) would allow the elimination of inter-cellular tissue-located micronuclei. ...
Pre-dive Whole-Body Vibration Better Reduces Decompression-Induced Vascular Gas Emboli than Oxygenation or a Combination of Both
Article
Full-text available
  • Nov 2016
Purpose: Since non-provocative dive profiles are no guarantor of protection against decompression sickness, novel means including pre-dive “preconditioning” interventions, are proposed for its prevention. This study investigated and compared the effect of pre-dive oxygenation, pre-dive whole body vibration or a combination of both on post-dive bubble formation. Methods: Six healthy volunteers performed 6 no-decompression dives each, to a depth of 33 mfw for 20 min (3 control dives without preconditioning and 1 of each preconditioning protocol) with a minimum interval of 1 week between each dive. Post-dive bubbles were counted in the precordium by two-dimensional echocardiography, 30 and 90 min after the dive, with and without knee flexing. Each diver served as his own control. Results: Vascular gas emboli (VGE) were systematically observed before and after knee flexing at each post-dive measurement. Compared to the control dives, we observed a decrease in VGE count of 23.8 ± 7.4% after oxygen breathing (p < 0.05), 84.1 ± 5.6% after vibration (p < 0.001), and 55.1 ± 9.6% after vibration combined with oxygen (p < 0.001). The difference between all preconditioning methods was statistically significant. Conclusions: The precise mechanism that induces the decrease in post-dive VGE and thus makes the diver more resistant to decompression stress is still not known. However, it seems that a pre-dive mechanical reduction of existing gas nuclei might best explain the beneficial effects of this strategy. The apparent non-synergic effect of oxygen and vibration has probably to be understood because of different mechanisms involved.
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... Aus Sicht der Autoren der Leitlinie ergibt sich unabhängig von der aktuellen wissenschaftlichen Diskussion über die pathophysiologischen Zusammenhänge der Dekompressionserkrankung [15][16][17] eine Empfehlung für die Ruhiglagerung des Opfers eines schweren Tauchunfalls. Bewegungen des Patienten sowie Vibrationen und Erschütterungen können die Menge intravaskulärer Gasblasen erhöhen ( [18], . ...
Diagnosis and treatment of diving accidents: New German guidelines for diving accidents 2014-2017
Article
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  • ANAESTHESIST
In 2015 the German Society for Diving and Hyperbaric Medicine (GTÜM) and the Swiss Underwater and Hyperbaric Medical Society (SUHMS) published the updated guidelines on diving accidents 2014-2017. These multidisciplinary guidelines were developed within a structured consensus process by members of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), the Sports Divers Association (VDST), the Naval Medical Institute (SchiffMedInst), the Social Accident Insurance Institution for the Building Trade (BG BAU), the Association of Hyperbaric Treatment Centers (VDD) and the Society of Occupational and Environmental Medicine (DGAUM). This consensus-based guidelines project (development grade S2k) with a representative group of developers was conducted by the Association of Scientific Medical Societies in Germany. It provides information and instructions according to up to date evidence to all divers and other lay persons for first aid recommendations to physician first responders and emergency physicians as well as paramedics and all physicians at therapeutic hyperbaric chambers for the diagnostics and treatment of diving accidents. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose and the following key action statements: on-site 100 % oxygen first aid treatment, still patient positioning and fluid administration are recommended. Hyperbaric oxygen (HBO) recompression remains unchanged the established treatment in severe cases with no therapeutic alternatives. The basic treatment scheme recommended for diving accidents is hyperbaric oxygenation at 280 kPa. For quality management purposes there is a need in the future for a nationwide register of hyperbaric therapy.
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Diving physiopathology: the end of certainties? Food for thought
Article
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Our understanding of decompression physiopathology has slowly improved during this last decade and some uncertainties have disappeared. A better understanding of anatomy and functional aspects of patent foramen ovale (PFO) have slowly resulted in a more liberal approach toward the medical fitness to dive for those bearing a PFO. Circulating vascular gas emboli (VGE) are considered the key actors in development of decompression sickness and can be considered as markers of decompression stress indicating induction of pathophysiological processes not necessarily leading to occurrence of disease symptoms. During the last decade, it has appeared possible to influence post-dive VGE by a so-called "preconditioning" as a pre-dive denitrogenation, exercise or some pharmacological agents. In the text we have deeply examined all the scientific evidence about this complicated but challenging theme. Finally, the role of the "normobaric oxygen paradox" has been clarified and it is not surprising that it could be involved in neuroprotection and cardioprotection. However, the best level of inspired oxygen and the exact time frame to achieve optimal effect is still not known. The aim of this paper was to reflect upon the most actual uncertainties and distil out of them a coherent, balanced advice towards the researchers involved in gas-bubbles-related pathologies.
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Preconditioning to Reduce Decompression Stress in Scuba Divers
Article
Full-text available
  • Feb 2017
Background: Using ultrasound imaging, vascular gas emboli (VGE) are observed after asymptomatic scuba dives and are considered a key element in the potential development of decompression sickness (DCS). Diving is also accompanied with vascular dysfunction, as measured by flow-mediated dilation (FMD). Previous studies showed significant intersubject variability to VGE for the same diving exposure and demonstrated that VGE can be reduced with even a single pre-dive intervention. Several preconditioning methods have been reported recently, seemingly acting either on VGE quantity or on endothelial inflammatory markers. Methods: Nine male divers who consistently showed VGE postdive performed a standardized deep pool dive (33 m/108 ft, 20 min in 33°C water temperature) to investigate the effect of three different preconditioning interventions: heat exposure (a 30-min session of dry infrared sauna), whole-body vibration (a 30-min session on a vibration mattress), and dark chocolate ingestion (30 g of chocolate containing 86% cocoa). Dives were made one day per week and interventions were administered in a randomized order. Results: These interventions were shown to selectively reduce VGE, FMD, or both compared to control dives. Vibration had an effect on VGE (39.54%, SEM 16.3%) but not on FMD postdive. Sauna had effects on both parameters (VGE: 26.64%, SEM 10.4%; FMD: 102.7%, SEM 2.1%), whereas chocolate only improved FMD (102.5%, SEM 1.7%). Discussion: This experiment, which had the same subjects perform all control and preconditioning dives in wet but completely standardized diving conditions, demonstrates that endothelial dysfunction appears to not be solely related to VGE.Germonpré P, Balestra C. Preconditioning to reduce decompression stress in scuba divers. Aerosp Med Hum Perform. 2017; 88(2):114-120.
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The pathway to drive decompression microbubbles from the tissues to the blood and the lymphatic system as a part of this transfer
Article
Full-text available
  • Jul 2009
  • UNDERSEA HYPERBAR M
The formation sites of the microbubbles that are routinely detected in the bloodstream at precordial level by Doppler after a decompression are reviewed and discussed here. First, microbubbles could form on the endothelium lumen wall of the capillaries, at specific nanometric sites, but the release mechanism of such small emerging entities remains puzzling. They could be also formed from pre-existing gas nuclei present in the blood when favorable local hydrodynamic/supersaturation conditions generate microcavitation and tribonucleation phenomena. Finally, tissues could represent large pools for microbubble formation and amplification. Nevertheless, it remains to explain what the potential pathways are to drive them to the blood. Knowing that the permeability of most of the blood capillary network is quite low, an alternative is proposed for such transport. The lymphatic system, which drains the interstitial fluid to guarantee the fluid balance of tissues, could allow the transfer of micrometric elements like stabilized microbubbles formed in tissues on long distances. A final rejection in the bloodstream at the termination of both right lymphatic and thoracic ducts can be expected. The characteristics of this slow transport, activated by the muscular pump, could explain the detection on long periods of massive venous gas emboli.
View
Pre-Dive Vibration Effect on Bubble Formation After a 30-m Dive Requiring a Decompression Stop
Article
Full-text available
  • Dec 2009
  • AVIAT SPACE ENVIR MD
The preconditioning of divers to reduce post-dive decompression sickness (DCS) has gained increased interest in diving medical research over the last few years. The beneficial effects of physical exercise, oxygen breathing, hyperbaric exposure, heat exposure, hyperhydration, or nitroglycerin administration before the dive are only a few examples of ongoing research. In this work, we investigated the effects of pre-dive whole-body vibration on post-dive bubble formation. Following French Navy standard dive procedures, 14 healthy male military divers performed 2 identical dives 1 wk apart to 30 m of seawater (msw) for 30 min. One of the dives was randomly preceded by a 30-min whole-body vibration session (frequencies 35-40 Hz) 1 h before the dive. Post-dive bubbles were measured precordially 30, 60, and 90 min after the dive and were graded according to the Kissman Integrated Severity Score (KISS) protocol, with and without knee flexing. Arterial endothelial function was measured before and after vibration using flow mediated dilation (FMD) measurement. A significant reduction in bubble scores was observed after the "vibration" dive. As there was no observed change in FMD after vibration, we do not believe a nitric oxide mediated mechanism is involved; rather, a mechanical dislodgement or enhanced lymphatic elimination of gas nuclei is hypothesized.
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The influence of multidirectional vibrations on wound healing and on regeneration of blood- and lymphvessels
Article
  • Jan 1982
Experiments show that the multidirectional vibration therapy is not an aggressive technique: when applied to the newly-formed lymph-vessels in the scar, we observed that they were not damaged by this technique whereas we had found in earlier studies that a gentle effleurage destructed the newly formed lymph network in the scar. When using this treatment, little or no adhesion of the scar to the underlying tissues is observed. There is a significant decrease of the local edema when compared to a standard group of wound-healing without multidirectional vibrations. There is also a significant decrease of general and local congestion and no increase in the permeability of veins and lymph vessels is present. The application of the local multidirectional vibration therapy accelerates the regeneration of the severed vein and lymph vessel.
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