Peter Germonpré

Predive Sauna and Venous Gas Bubbles Upon Decompression from 400 kPa

INTRODUCTION This study investigated the influence of a far infrared-ray dry sauna-induced heat exposure before a simulated dive on bubble formation, and examined the concomitant adjustments in hemodynamic parameters. METHODS There were 16 divers who were compressed in a hyperbaric chamber to 400 kPa (30 msw) for 25 min and decompressed at 100 kPa x min(-1) with a 4-min stop at 130 kPa. Each diver performed two dives 5 d apart, one with and one without a predive sauna session for 30 min at 65 degrees C ending 1 h prior to the dive. Circulating venous bubbles were detected with a precordial Doppler 20, 40, and 60 min after surfacing, at rest, and after flexions. Brachial artery flow mediated dilation (FMD), blood pressure, and bodyweight measurements were taken before and after the sauna session along with blood samples for analysis of plasma volume (PV), protein concentrations, plasma osmolality, and plasma HSP70. RESULTS A single session of sauna ending 1 h prior to a simulated dive significantly reduced bubble formation [-27.2% (at rest) to 35.4% (after flexions)]. The sauna session led to an extracellular dehydration, resulting in hypovolemia (-2.7% PV) and -0.6% bodyweight loss. A significant rise of FMD and a reduction in systolic blood pressure and pulse pressure were observed. Plasma HSP70 significantly increased 2 h after sauna completion. CONCLUSION A single predive sauna session significantly decreases circulating bubbles after a chamber dive. This may reduce the risk of decompression sickness. Sweat dehydration, HSP, and the NO pathway could be involved in this protective effect.

Long term effects of recreational SCUBA diving on higher cognitive function.

We investigated long‐term effects of SCUBA diving on cognitive function using a battery of neuropsychometric tests: the Simple Reaction Time (REA), Symbol Digit Substitution (SDS), Digit Span Backwards (DSB), and Hand‐Eye Coordination tests (EYE). A group (n = 44) of experienced SCUBA divers with no history of decompression sickness was compared to non‐diving control subjects (n = 37), as well as to professional boxers (n = 24), who are considered at higher risk of long term neurological damage. The REA was significantly shorter in SCUBA divers compared to the control subjects, and also more stable over the time course of the test. In contrast, the number of digits correctly memorized and reordered (DSB) was significantly lower for SCUBA divers compared to the control group. The results also showed that boxers performed significantly worse than the control group in three out of four tests (REA, DSB, EYE). While it may be concluded that accident‐free SCUBA diving may have some long‐term adverse effects on short‐term memory, there is however, no evidence of general higher cognitive function deficiency.

Correlation between Patent Foramen Ovale, Cerebral “Lesions” and Neuropsychometric Testing in Experienced Sports Divers: Does Diving Damage the Brain?

SCUBA diving exposes divers to decompression sickness (DCS). There has been considerable debate whether divers with a Patent Foramen Ovale of the heart have a higher risk of DCS because of the possible right-to-left shunt of venous decompression bubbles into the arterial circulation. Symptomatic neurological DCS has been shown to cause permanent damage to brain and spinal cord tissue; it has been suggested that divers with PFO may be at higher risk of developing subclinical brain lesions because of repeated asymptomatic embolization of decompression-induced nitrogen bubbles. These studies however suffer from several methodological flaws, including self-selection bias. We recruited 200 volunteer divers from a recreational diving population who had never suffered from DCS; we then randomly selected 50 of those for further investigation. The selected divers underwent brain Magnetic Resonance Imaging to detect asymptomatic brain lesions, contrast trans-oesophageal echocardiography for PFO, and extensive neuro-psychometric testing. Neuro-psychometry results were compared with a control group of normal subjects and a separate control group for subjects exposed to neurotoxic solvents. Forty two divers underwent all the tests and are included in this report. Grade 2 Patent Foramen Ovale was found in 16 (38%) of the divers; brain Unidentified Bright Objects (UBOs) were found in 5 (11.9%). There was no association between PFO and the presence of UBOs (P = 0.693) or their size (p = 0.5) in divers. Neuropsychometric testing in divers was significantly worse from controls in two tests, Digit Span Backwards (DSB; p < 0.05) and Symbol-Digit-Substitution (SDS; p < 0.01). Compared to subjects exposed to neurotoxic solvents, divers scored similar on DSB and SDS tests, but significantly better on the Simple Reaction Time (REA) and Hand-Eye Coordination (EYE) tests. There was no correlation between PFO, number of UBOs and any of the neuro-psychometric tests. We conclude that for uneventful recreational diving, PFO does not appear to influence the presence of UBOs. Diving by itself seems to cause some decrease of short-term memory and higher cognitive function, including visual-motor skills; this resembles some of the effects of nitrogen narcosis and we suggest that this may be a prolonged effect of diving.

Passive flooding of paranasal sinuses and middle ears as a method of equalisation in extreme breath-hold diving

Breath-hold diving is both a recreational activity, performed by thousands of enthusiasts in Europe, and a high-performance competitive sport. Several ‘disciplines’ exist, of which the ‘no-limits’ category is the most spectacular: using a specially designed heavy ‘sled,’ divers descend to extreme depths on a cable, and then reascend using an inflatable balloon, on a single breath. The current world record for un-assisted descent stands at more than 200 m of depth. Equalising air pressure in the paranasal sinuses and middle-ear cavities is a necessity during descent to avoid barotraumas. However, this requires active insufflations of precious air, which is thus unavailable in the pulmonary system. The authors describe a diver who, by training, is capable of allowing passive flooding of the sinuses and middle ear with (sea) water during descent, by suppressing protective (parasympathetic) reflexes during this process. Using this technique, he performed a series of extreme-depth breath-hold dives in June 2005, descending to 209 m of sea water on one breath of air.

EPO and doping.

It is with great interest that we read exchanges on intermittent hypoxic (Boning 2009; Ferretti 2009) exposure as a potential doping procedure. Erythropoietin (EPO) does introduce potential concerns in terms of doping, both due to its eVects and side eVects. An earlier publication on exogenous EPO (Noakes 2008) clearly showed an increase of sub-maximal performance with a signiWcant increase of time to exhaustion after prolonged rHuEPO administration. It is clear that in healthy subjects, at sub-maximal eVort levels, cardiac output is suYcient to maintain adequate oxygen delivery to active muscles. Accordingly, it appears that EPO achieves more than increasing blood oxygen carrying capacity alone. Being both a hormone and a cytokine, the actual actions of EPO are complex: EPO is neuroprotective and even neuroregenerative in both the peripheral and central nervous system. Moreover, EPO also has antiapoptotic eVects that may be coupled to antioxidant activity. Exercise-induced plasma volume contraction is linked to EPO production (Roberts et al. 2000), whereas the hormone itself appears to alter plasma volume as well. Any of these known actions of EPO could explain a possible increase in exercise capacity. The traditional view of EPO as a haemopoietic agent, therefore, needs to be expanded to incorporate these additional eVects and studies on the eVects of EPO should be designed in such a way that these may be considered more carefully. Urine testing for exogenous EPO has been available for several years. It has been used in international cycling events. However, this does not exclude the possibility of endogenous EPO induction. Intermittent hypoxia (SanchisGomar et al. 2009) is the natural trigger for EPO production, and is widely used by (endurance) athletes since many years. We have recently described the use of intermittent hyperoxia to stimulate EPO production (Balestra et al. 2006). This has subsequently been shown to be capable of increasing haemoglobin levels in a chronically anaemic patient (Burk 2007). The mechanism proposed to explain this “normobaric oxygen paradox” involves a complex play of oxygen-free radicals (OFRs) presence and their “scavenging” enzymes in the cell. In the presence of OFR, the continuously produced hypoxia-inducible factor alpha (HIF-1 ) is instantly linked to the (tumour suppressing) Von Hippel Lindau Protein (VHLp). This complex is subsequently ubiquitinized in the prolyl-oxidase pathway and Wnally recycled in the proteasome. In a hypoxic state, the absence of OFR prevents HIF-1 from linking to VHLp, and allows it to be dimerized with the HIF-1 dimer. This hybrid HIF complex can then start a cascade of EPO gene expression and subsequently, de novo EPO synthesis. In a hyperoxic situation, the presence of OFR will trigger an upregulation of OFR scavenging systems; notably, the activity of the glutathione synthetase enzyme is increased, resulting in an increased availability of glutathione. When now the cell resumes its “normoxic” state, the increased glutathione will scavenge all OFRs present, “mimicking” a hypoxic situation, and allowing the HIF dimers to bind and start the EPO gene expression. In our experience, this mechanism has allowed a clinically valuable increase in haemoglobin in patients with anaemia due to a variety of causes, including bone marrow Communicated by Susan Ward.

Pre-dive Whole-Body Vibration Better Reduces Decompression-Induced Vascular Gas Emboli than Oxygenation or a Combination of Both

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.

Preconditioning to Reduce Decompression Stress in Scuba Divers

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.

Hypoxia, a multifaceted phenomenon: the example of the “Normobaric Oxygen Paradox”

Janus, a double-faced Roman god, was the god of beginnings and ends, and has given his name to the Wrst month of the year. The state of “hypoxia” as a trigger for EPO seems “to fool Janus” since, as an actual and ongoing debate shows, both the degree and duration of the “hypoxic” stimulus as well as correlated physiological reactions and states can make or break the eVect—a more than double-faceted phenomenon (Lippi et al. 2011). When considering the recent and ongoing research into the eVects and mechanisms of the “Normobaric Oxygen Paradox” (NOP), Wrst described by our group in 2006 (Balestra et al. 2006) as being capable of inducing endogenous Erythropoietin (EPO) production, the following statements can now be made: First, the sequence: a steady-state hypoxic condition seems to be less eVective in triggering EPO production than an intermittent stimulus mode. For instance, to trigger EPO during a stay at altitude, one needs an exposure of several days (Christoulas et al. 2011) whereas an intermittent stimulus apparently needs just 36–48 h (Balestra et al. 2006; Brugniaux et al. 2011; Theunissen et al. 2011). The time needed to increase reticulocyte count and thus hematocrit can be signiWcantly decreased by “live high, train low” procedures (Martinez-Bello et al. 2011). It appears that hypoxia-induced physiological reactions are more likely dependent on “changes in oxygen levels” than on the mere hypoxic state itself. Second, the dose: the absolute level of hypoxia seems not to be mandatory to achieve an eVect. In fact, our Wrst paper proposed that the return of a hyperoxic state back to normoxia can be understood as a “hypoxic stimulus” in humans (Balestra et al. 2006). A period of moderate hyperoxia will induce up-regulation of glutathione synthetase, resulting in a more eYcient disposal of Reactive Oxygen Species (ROS) when normoxia is restored (Dekerle et al. 2011). This eVect causes ROS levels to decrease, similar to a state of “true hypoxia”. However, in our initial results we have demonstrated that hyperbaric oxygen at 2.5 atmospheres absolute did not produce the same increase in EPO as normobaric oxygen, but on the contrary caused a suppression (hence the term “Normobaric Oxygen Paradox”). In our proposed mechanism, this could be explained by a depletion of reduced glutathione when faced with too high an increase of ROS. Our group (De Bels et al. 2011) has also shown that normobaric oxygen, given too often (Theunissen et al. 2011), is not as eVective in increasing EPO or hemoglobin levels. The minimal concentration of inspired oxygen seems to lie around 50 % (Ciccarella et al. 2011), increasing the inspired oxygen fraction to 100 % giving variable and less consistent results. Further investigations to determine the optimal “dose” are clearly needed, and the recent publications by Keramides and Mekjavic (Keramidas et al. 2011a, b) conWrm the fact that giving 100 % oxygen is not optimal. Furthermore, increasing the diVerence in oxygenation (by moving from normobaric hyperoxia to nomobaric hypoxia) seems to be likewise suppressive of EPO (Debevec et al. 2011). Our recent Wndings on HUVEC cells (Human umbilical vein endothelial cells) (unpublished results) show a decrease of HIF-1 alpha expression after 2 h of hyperoxia (32 % oxygen) to 0.59 % of control, followed 4 and 6 h after return to normoxia by increases of 119.1 and 176.6 %, respectively. Communicated by Susan A. Ward.

Increasing EPO using the normobaric oxygen paradox: a 'not so simple' task.

Since the first report presenting the possibility to increase erythropoietin (EPO) with a single nonhypoxic stimulus (Balestra et al. 2006), its clinical utility has been postulated in neuroprotection and cardioprotection as a pre-operative treatment, as well as in the treatment of sepsis patients (Calzia et al. 2010). The repetition of this simple stimulus has been used to increase haemoglobin and reticulocytes in anaemic patients (Burk 2007, Balestra et al. 2010). The possible ‘doping-like’ effect of such a method has also been recently discussed (Balestra & Germonpre 2010). Although the normobaric oxygen paradox (NOP) mechanism seems to be proved, our experience demonstrates that to effectively show a significant increase in EPO after one single exposure to normobaric oxygen is not so easy. Several concomitant mechanisms are involved here. The individual circadian rhythm of erythropoietin production: Hormonal variations depend on circadian as well as seasonal rhythms (Keramidas et al. 2011). To show an increase at a specific moment of the day we found that a simple correction for baseline levels matching was not sufficient and an individual matching of the circadian rhythm was needed (Balestra et al. 2006). The modest acute increase in EPO was shown to be effective to increase haemoglobin when repeated for several days (Burk 2007). The effective amount and activity of glutathione of the subjects: In some cases, we could not find a clear increase of EPO in some individuals, usually subjects who were older or physically inactive. This may be related to a decreased intracellular glutathione content. It has recently been shown that repletion of glutathione intracellular reserve can be effective on EPO production (Zembron-Lacny et al. 2010): supplementing N-acetyll-cysteine (NAC) was useful in young healthy subjects to increase EPO after 8 days of treatment, without oxygen sessions. This approach has also been shown to be effective, a single oxygen session with concomitant supplementation of NAC being able to increase EPO production. In hyperbaric oxygen sessions, NAC has been used to reduce ‘toxic oxygen effects’ and is still used for hyperbaric oxygen (HBO) preconditioning (Pelaia et al. 1995). As an upregulation of glutathione synthetase is induced by repetitive exposures to higher oxygen levels, the repetitive short normobaric oxygen sessions could well increase glutathione activity or available amount. This needs to be considered when interpreting acute EPO production, as an increase in haemoglobin levels has been shown using the NOP in non-healthy subjects, considered at a less than maximal efficiency or availability of glutathione. The dose of oxygen given: Since the beginning we understood that a too high dose of oxygen given was responsible for a decrease in EPO (our initial results showed that hyperbaric oxygen therapy was suppressing EPO in a very significant way) and of course this can be explained by the glutathione activity depletion when faced with a drastic increase in reactive oxygen species. This phenomenon, when adequately used, has been postulated to be beneficial for cancer (De Bels et al. 2011). We have also experienced that normobaric oxygen, given at too high concentrations or even too often, was not as effective to increase EPO or haemoglobin. The minimal concentration of oxygen to trigger the NOP seems to lay around 40%, raising the inspired oxygen fraction too close to 100% shows very variable results. We do not know the optimal dose or the optimal frequency but we still encourage investigations on that topic. In conclusion, we want to draw the readers’ attention to the rather fine-tuning that seems to underlie the appropriate use of the normobaric oxygen paradox, in particular to be able to show a significant increase in EPO at a specific moment after one single oxygen exposure. Reticulocytes and consequent haemoglobin increase needs several exposures at specific time frames. The optimal inspired fraction and the optimal session schedule is not known at the moment; NAC supplementation seems to be of benefit. The optimal way of using the NOP lies certainly in a combination of all of the above-mentioned factors. Jumping too fast to conclusions when reporting mitigated results (possibly when applying less than optimal stimuli) could wrongly refrain us from using a simple, inexpensive, safe and greatly beneficial phenomenon in the clinical setting.

Pulmonary barotrauma in divers during emergency free ascent training: review of 124 cases.

INTRODUCTION Experience from treating diving accidents indicates that a large proportion of divers suffering from pulmonary barotraumas (PBT) or arterial gas embolism (AGE) were engaged in training dives, specifically emergency free ascent (EFA). We tried to verify this relationship and to calculate, if possible, the risk associated with normal recreational dives, training dives, and EFA training dives. METHODS All diving accidents treated at the Centre for Hyperbaric Oxygen Therapy (Brussels, Belgium) from January 1995 until October 2005 were reviewed. Data on the average number of dives performed and the proportion of in-water skills training dives were obtained from the major Belgian dive associations. RESULTS A total of 124 divers were treated, of whom 34 (27.4%) were diagnosed with PBT. Of those, 20 divers (58.8%) had symptoms of AGE. In 16 of those, EFA training exercise was deemed responsible for the injury. The association between EFA training and PBT proved to be very significant, with an odds ratio of 11.33 (95% confidence interval: 2.186 to 58.758). It was possible to calculate that a training dive (0.456 to 1.36/10,000) carries a 100 to 400 times higher risk, and an ascent training dive (1.82 to 5.46/10,000 dives) a 500 to 1500 times higher risk for PBT than a non-training dive (0.0041 to 0.0043/10,000 dives). DISCUSSION This study confirms a significant association between EFA training dives and the occurrence of PBT.