Blood Adenosine Increase During Apnea in Spearfishermen Reinforces the Efficiency of the Cardiovascular Component of the Diving Reflex.

The physiopathology consequences of hypoxia during breath-hold diving are a matter of debate. Adenosine (AD), an ATP derivative, is suspected to be implicated in the adaptive cardiovascular response to apnea, because of its vasodilating and bradycardic properties, two clinical manifestations observed during voluntary apnea. The aim of this study was to evaluate the adenosine response to apnea-induced hypoxia in trained spearfishermen (SFM) who are used to perform repetitive dives for 4-5 h. Twelve SFM (11 men and 1 woman, mean age 41 ± 3 years, apnea experience: 18 ± 9 years) and 10 control (CTL) subjects (age 44 ± 7 years) were enrolled in the study. Subjects were asked to main a dry static apnea and stopped it when they began the struggle phase (average duration: SFM 120 ± 78 s, CTL 78 ± 12 s). Capillary blood samples were collected at baseline and immediately after the apnea and analyzed for standard parameters and adenosine blood concentration ([AD]b). Heart rate (HR), systolic (SBP), and diastolic (DBP) blood pressures were also recorded continuously during the apnea. During the apnea, an increase in SBP and DBP and a decrease in HR were observed in both SFM and CTL. At baseline, [AD]b was higher in SFM compared with CTL (1.05 ± 0.2 vs. 0.73 ± 0.11 µM, p < 0.01). [AD]b increased significantly at the end of the apnea in both groups, but the increase was significantly greater in SFM than in controls (+90.4 vs. +12%, p < 0.01). Importantly, in SFM, we also observed significant correlations between [AD]b and HR (R = -0.8, p = 0.02), SpO2 (R = -0.69, p = 0.01), SBP (R = -0.89, p = 0.02), and DBP (R = -0.68, p = 0.03). Such associations were absent in CTL. The adenosine release during apnea was associated with blood O2 saturation and cardiovascular parameters in trained divers but not in controls. These data therefore suggest that adenosine may play a major role in the adaptive cardiovascular response to apnea and could reflect the level of training.

Underwater and Surface Swimming Parameters Reflect Performance Level in Elite Swimmers.

Although the role of underwater phases is well-known, no study has taken an interest in describing and quantifying the distance and time spent in apnea as a condition for optimal performance. This study aimed to investigate the impact of time and distance spent underwater and surface parameters on the swimming performance of elite swimmers. The performances of 79 swimmers in 100-m freestyle were analyzed (short-course). The underwater and spatiotemporal parameters of three groups have been recorded: finalists of the 2018 World Swimming Championships (WORLD), French swimmers who reached a 100 m performance time under 50 s at the 2018 French National Championships (UND50), and those who reached a 100 m performance time above 50 s (UP50). The WORLD group spent more distance underwater (37.50 ± 4.92 m) in comparison with UND50 (31.90 ± 4.88 m, p < 0.05) and UP50 (31.94 ± 4.93 m, p < 0.01) groups. The total percentage of non-swimming time was higher for WORLD (39.11 ± 4.73%) vs. UND50 (34.21 ± 4.55%, p < 0.05) and UP50 (33.94 ± 5.00%, p < 0.01). In addition, underwater speed was higher for WORLD (2.54 ± 0.05 m/s) compared with UND50 (2.46 ± 0.09 m/s, p < 0.05) and UP50 (2.38 ± 0.11 m/s, p < 0.01). Three parameters among the underwater phases (i.e. distance underwater, speed underwater, and total percentage of non-swimming time) determine the 100-m freestyle short course performance. These data suggest an appropriate focus on specific apnea training to improve underwater skills during short-course swimming performances.

Exponential Relationship Between Maximal Apnea Duration and Exercise Intensity in Non-apnea Trained Individuals.

It is well known that the duration of apnea is longer in static than in dynamic conditions, but the impact of exercise intensity on the apnea duration needs to be investigated. The aim of this study was to determine the relationship between apnea duration and exercise intensity, and the associated metabolic parameters. Ten healthy active young non-apnea trained (NAT) men participated in this study. During the first visit, they carried out a maximum static apnea (SA) and a maximal progressive cycle exercise to evaluate the power output achieved at peak oxygen uptake (PVO2peak). During the second visit, they performed four randomized dynamic apneas (DAs) at 20, 30, 40, and 50% of PVO2peak (P20, P30, P40, and P50) preceded by 4 min of exercise without apnea. Duration of apnea, heart rate (HR), arterial oxygen saturation (SpO2), blood lactate concentration [La], rating of perceived exertion (RPE), and subjective feeling were recorded. Apnea duration was significantly higher during SA (68.1 ± 23.6 s) compared with DA. Apnea duration at P20 (35.6 ± 11.7 s) was higher compared with P30 (25.6 ± 6.3 s), P40 (19.2 ± 6.7 s), and P50 (16.9 ± 2.5 s). The relationship between apnea duration and exercise intensity followed an exponential function (y = 56.388e-0.025 x ). SA as DA performed at P20 and P30 induces a bradycardia. Apnea induces an SpO2 decrease which is higher during DA (-10%) compared with SA (-4.4%). The decreases of SPO2 recorded during DA do not differ despite the increase in exercise intensity. An increase of [La] was observed in P30 and P40 conditions. RPE and subjective feeling remained unchanged whatever the apnea conditions might be. These results suggest that the DA performed at 30% of VO2peak could be the best compromise between apnea duration and exercise intensity. Then, DA training at low intensity could be added to aerobic training since, despite the moderate hypoxia, it is sufficient to induce and increase [La] generally observed during high-intensity training.

Physiological stress markers during breath-hold diving and SCUBA diving.

This study investigated the sources of physiological stress in diving by comparing SCUBA dives (stressors: hydrostatic pressure, cold, and hyperoxia), apneic dives (hydrostatic pressure, cold, physical activity, hypoxia), and dry static apnea (hypoxia only). We hypothesized that despite the hypoxia induces by a long static apnea, it would be less stressful than SCUBA dive or apneic dives since the latter combined high pressure, physical activity, and cold exposure. Blood samples were collected from 12SCUBA and 12 apnea divers before and after dives. On a different occasion, samples were collected from the apneic group before and after a maximal static dry apnea. We measured changes in levels of the stress hormones cortisol and copeptin in each situation. To identify localized effects of the stress, we measured levels of the cardiac injury markers troponin (cTnI) and brain natriuretic peptide (BNP), the muscular stress markers myoglobin and lactate), and the hypoxemia marker ischemia-modified albumin (IMA). Copeptin, cortisol, and IMA levels increased for the apneic dive and the static dry apnea, whereas they decreased for the SCUBA dive. Troponin, BNP, and myoglobin levels increased for the apneic dive, but were unchanged for the SCUBA dive and the static dry apnea. We conclude that hypoxia induced by apnea is the dominant trigger for the release of stress hormones and cardiac injury markers, whereas cold or and hyperbaric exposures play a minor role. These results indicate that subjects should be screened carefully for pre-existing cardiac diseases before undertaking significant apneic maneuvers.

Troponins in scuba divers with immersion pulmonary edema.

Immersion pulmonary edema (IPE) is a serious complication of water immersion during scuba diving. Myocardial ischemia can occur during IPE that worsens outcome. Because myocardial injury impacts the therapeutic management, we aim to evaluate the profile of cardiac markers (creatine phosphokinase (CPK), brain natriuretic peptide (BNP), highly sensitive troponin T (TnT-hs) and ultrasensitive troponin I (TnI-us) of divers with IPE. Twelve male scuba divers admitted for suspected IPE were included. The collection of blood samples was performed at hospital entrance (T0) and 6 h later (T0 + 6 h). Diagnosis was confirmed by echocardiography or computed-tomography scan. Mean ± S.D. BNP (pg/ml) was 348 ± 324 at T0 and 223 ± 177 at T0 + 6 h (P<0.01), while mean CPK (international units (IUs)), and mean TnT-hs (pg/ml) increased in the same times 238 ± 200 compared with 545 ± 39, (P=0.008) and 128 ± 42 compared with 269 ± 210, (P=0.01), respectively; no significant change was observed concerning TnI-us (pg/ml): 110 ± 34 compared with 330 ± 77, P=0.12. At T0 + 6 h, three patients had high TnI-us, while six patients had high TnT-hs. Mean CPK was correlated with TnT-hs but not with TnI-us. Coronary angiographies were normal. The increase in TnT during IPE may be secondary to the release of troponin from non-cardiac origin. The measurement of TnI in place of TnT permits in some cases to avoid additional examinations, especially unnecessary invasive investigations.

The oxygen-conserving potential of the diving response: A kinetic-based analysis.

We investigated the oxygen-conserving potential of the human diving response by comparing trained breath-hold divers (BHDs) to non-divers (NDs) during simulated dynamic breath-holding (BH). Changes in haemodynamics [heart rate (HR), stroke volume (SV), cardiac output (CO)] and peripheral muscle oxygenation [oxyhaemoglobin ([HbO2]), deoxyhaemoglobin ([HHb]), total haemoglobin ([tHb]), tissue saturation index (TSI)] and peripheral oxygen saturation (SpO2) were continuously recorded during simulated dynamic BH. BHDs showed a breaking point in HR kinetics at mid-BH immediately preceding a more pronounced drop in HR (-0.86 bpm.%-1) while HR kinetics in NDs steadily decreased throughout BH (-0.47 bpm.%-1). By contrast, SV remained unchanged during BH in both groups (all P > 0.05). Near-infrared spectroscopy (NIRS) results (mean ± SD) expressed as percentage changes from the initial values showed a lower [HHb] increase for BHDs than for NDs at the cessation of BH (+24.0 ± 10.1 vs. +39.2 ± 9.6%, respectively; P < 0.05). As a result, BHDs showed a [tHb] drop that NDs did not at the end of BH (-7.3 ± 3.2 vs. -3.0 ± 4.7%, respectively; P < 0.05). The most striking finding of the present study was that BHDs presented an increase in oxygen-conserving efficiency due to substantial shifts in both cardiac and peripheral haemodynamics during simulated BH. In addition, the kinetic-based approach we used provides further credence to the concept of an "oxygen-conserving breaking point" in the human diving response.

Hyperoxia Improves Hemodynamic Status During Head-up Tilt Testing in Healthy Volunteers: A Randomized Study.

Head-up tilt test is useful for exploring neurally mediated syncope. Adenosine is an ATP derivative implicated in cardiovascular disturbances that occur during head-up tilt test. The aim of the present study was to investigate the impact of hyperoxia on adenosine plasma level and on hemodynamic changes induced by head-up tilt testing.Seventeen healthy male volunteers (mean age 35 ±â€Š11 years) were included in the study. The experiment consisted of 2 head-up tilt tests, 1 session with subjects breathing, through a mask, medical air (FiO2 = 21%) and 1 session with administration of pure oxygen (FiO2 = 100%) in double-blind manner. Investigations included continuous monitoring of hemodynamic data and measurement of plasma adenosine levels.No presyncope or syncope was found in 15 of the 17 volunteers. In these subjects, a slight decrease in systolic blood pressure was recorded during orthostatic stress performed under medical air exposure. In contrast, hyperoxia led to increased systolic blood pressure during orthostatic stress when compared with medical air. Furthermore, mean adenosine plasma levels decreased during hyperoxic exposure before (0.31 ±â€Š0.08 µM) and during head-up tilt test (0.33 ±â€Š0.09 µM) when compared with baseline (0.6 ±â€Š0.1 µM). Adenosine plasma level was unchanged during medical air exposure at rest (0.6 ±â€Š0.1 µM), and slightly decreased during orthostatic stress. In 2 volunteers, the head-up tilt test induced a loss of consciousness when breathing air. In these subjects, adenosine plasma level increased during orthostatic stress. In contrast, during hyperoxic exposure, the head-up tilt test did not induce presyncope or syncope. In these 2 volunteers, biological study demonstrated a decrease in adenosine plasma level at both baseline and during orthostatic stress for hyperoxic exposure compared with medical air.These results suggest that hyperoxia was able to increase blood pressure during head-up tilt test via a decrease in plasma adenosine concentration. Our results also suggest that adenosine receptor antagonists are worth trying in neurocardiogenic syncope.

Activation of human inspiratory muscles in an upside-down posture.

During quiet breathing, activation of obligatory inspiratory muscles differs in timing and magnitude. To test the hypothesis that this coordinated activation can be modified, we determined the effect of the upside-down posture compared with standing and lying supine. Subjects (n=14) breathed through a pneumotachometer with calibrated inductance bands around the chest wall and abdomen. Surface electromyographic activity (EMG) was recorded from the scalene muscles. Crural diaphragmatic EMG and oesophageal and gastric pressures were measured in a subset of six subjects. Quiet breathing and standard lung function manoeuvres were performed. The upside-down posture reduced end-expiratory lung volume. During quiet breathing, for the same inspiratory airflow and tidal volume, ribcage contribution decreased, abdominal contribution increased and transdiaphragmatic pressure swing doubled in the upside-down posture compared to standing (p<0.05). Despite this, crural diaphragm EMG was unchanged, whereas scalene muscle EMG was reduced by ∼half (p<0.05). Thus, the mechanical effect of an upside-down posture differentially affects inspiratory muscle activation.

Endogenous adenosine release is involved in the control of heart rate in rats.

Intravenous (i.v.) injections of adenosine exert marked effects on heart rate (HR) and arterial blood pressure (BP), but the role of an endogenous adenosine release by vagal stimulation has not been evaluated. In anaesthetized rats, we examined HR and BP changes induced by 1 min electrical vagal stimulation in the control condition, and then after i.v. injections of (i) atropine, (ii) propranolol, (iii) caffeine, (iv) 8 cyclopentyl-1,3-dipropylxanthine (DPCPX), or (v) dipyridamole to increase the plasma concentration of adenosine (APC). APC was measured by chromatography in the arterial blood before and at the end of vagal stimulation. The decrease in HR in the controls during vagal stimulation was markedly attenuated, but persisted after i.v. injections of atropine and propranolol. When first administered, DPCPX modestly but significantly reduced the HR response to vagal stimulation, but this disappeared after i.v. caffeine administration. Both the HR and BP responses were significantly accentuated after i.v. injection of dipyridamole. Vagal stimulation induced a significant increase in APC, proportional to the magnitude of HR decrease. Our data suggest that the inhibitory effects of electrical vagal stimulations on HR and BP were partly mediated through the activation of A1 and A2 receptors by an endogenous adenosine release. Our experimental data could help to understand the effects of ischemic preconditioning, which are partially mediated by adenosine.

Ischaemia-modified albumin during experimental apnoea.

Ischaemia-modified albumin (IMA) is a marker of the release of reactive oxygen species (ROS) during hypoxaemia. In elite divers, breath-hold induces ROS production. Our aim was to evaluate the kinetics of IMA serum levels during apnea. Twenty breath-hold divers were instructed to perform a submaximal static breath-hold. Twenty non-diver subjects served as controls. Blood samples were collected at rest, every minute, at the end of breath-hold, and 10 min after recovery. The IMA level increased after 1 min of breath-hold (p < 0.003) and remained high until recovery. Divers were separated into 2 groups: subjects who held their breath for less than 4 min (G-4) and those who held it for more than 4 min (G+4). After 3 min of apnoea, the increase of IMA was higher in the G-4 group than in the G+4 group (p < 0.008). However, at the end of apnoea, the IMA level did not differ between groups. If IMA level was globally correlated with the apnoea duration, it is interesting to note that the higher IMA level was not found in the best divers. Similarly, if arterial blood oxygen saturation (SpO2) was globally inversely correlated with apnoea duration, the lowest SpO2 at the end of breath-hold was not found in the divers that performed the best apnoea. We concluded that these divers save their oxygen. The IMA level provides a useful measure of resistance to hypoxaemia.

Modeling the diving bradycardia: Toward an "oxygen-conserving breaking point"?

PURPOSE: Although it has been demonstrated that the exponential decay model fits the heart rate (HR) kinetics in short static breath holding (BH), this model might be inaccurate when BH is maintained for several minutes. The aim of this study was to build a new meaningful model to quantify HR kinetics during prolonged static BH. METHODS: Nonlinear regression analysis was used to build a model able to quantify the beat-to-beat HR reduction kinetics observed in prolonged static BH performed both in air and in immersed condition by 11 trained breath-hold divers. Dynamic changes in cardiac autonomic regulation through heart rate variability indices [root mean square of successive difference of R-R intervals (RMSSD); short-term fractal scaling exponent: (DFAα1)] and peripheral oxygen saturation (SpO2) were also analyzed to strengthen the model. RESULTS: The tri-phasic model showed a sharp exponential drop in HR immediately followed by a slight linear rise up until a breaking point preceding a linear drop in HR. The breaking points had similar level of SpO2 whether in air or in immersed condition (95.1 ± 2.1 vs. 95.2 ± 3.0 %, respectively; P = 0.49), and the subsequent linear drop in HR was concomitant with a shift in cardiac autonomic regulation in air (RMSSD: +109.0 ± 47.8 %; P < 0.001; DFAα1: -18.0 ± 17.4 %; P < 0.05) and in immersion (RMSSD: +112.6 ± 55.8 %; P < 0.001; DFAα1: -26.0 ± 12 %; P < 0.001). CONCLUSION: In addition to accurately fitting the HR kinetics, the most striking finding is an "oxygen-conserving breaking point" highlighted by the model, which might be interpreted as unique adaptive feature against hypoxic damages in the human diving bradycardia.

Apnea: a new training method in sport?

The physiological responses to apnea training exhibited by elite breath-hold divers may contribute to improving sports performance. Breath-hold divers have shown reduced blood acidosis, oxidative stress and basal metabolic rate, and increased hematocrit, erythropoietin concentration, hemoglobin mass and lung volumes. We hypothesise that these adaptations contributed to long apnea durations and improve performance. These results suggest that apnea training may be an effective alternative to hypobaric or normobaric hypoxia to increase aerobic and/or anaerobic performance.

Circulatory effects of apnoea in elite breath-hold divers.

AIM: Voluntary apnoea induces several physiological adaptations, including bradycardia, arterial hypertension and redistribution of regional blood flows. Elite breath-hold divers (BHDs) are able to maintain very long apnoea, inducing severe hypoxaemia without brain injury or black-out. It has thus been hypothesized that they develop protection mechanisms against hypoxia, as well as a decrease in overall oxygen uptake. METHODS: To test this hypothesis, the apnoea response was studied in BHDs and non-divers (NDs) during static and dynamic apnoeas (SA, DA). Heart rate, arterial oxygen saturation (SaO(2)), and popliteal artery blood flow were recorded to investigate the oxygen-conserving effect of apnoea response, and the internal carotid artery blood flow was used to examine the mechanisms of cerebral protection. RESULTS: The bradycardia and peripheral vasoconstriction were accentuated in BHDs compared with NDs (P < 0.01), in association with a smaller SaO(2) decrease (-2.7% vs. -4.9% during SA, P < 0.01 and -6% vs. -11.3% during DA, P < 0.01). Greater increase in carotid artery blood flow was also measured during apnoea in BHDs than in controls. CONCLUSION: These results confirm that elite divers present a potentiation of the well-known apnoea response in both SA and DA conditions. This response is associated with higher brain perfusion which may partly explain the high levels of world apnoea records.

Static apnea effect on heart rate and its variability in elite breath-hold divers.

BACKGROUND: The diving response includes cardiovascular adjustments known to decrease oxygen uptake and thus prolong apnea duration. As this diving response is in part characterized by a pronounced decrease in heart rate (HR), it is thought to be vagally mediated. METHODS: In five professional breath-hold divers (BHDs) and five less-trained controls (CTL), we investigated whether the diving response is in fact associated with an increase in the root mean square successive difference of the R-R intervals (RMSSD), a time-domain heart rate variability (HRV) index. HR behavior and arterial oxygen saturation (SaO2) were continuously recorded during one maximal apnea. Short-term changes in SaO2, HR, and RMSSD were calculated over the complete apnea duration. RESULTS: BHDs presented bi-phasic HR kinetics, with two HR decreases (32 +/- 17% and 20 +/- 10% of initial HR). The second HR decrease, which was concomitant to the pronounced SaO2 decrease, was also simultaneous to a marked increase in RMSSD. CTL showed only one HR decrease (50 +/- 10% of initial HR), which appeared before the concomitant SaO2 and RMSSD changes. When all subject data were combined, arterial desaturation was positively correlated with total apnea time (r = 0.87, P < 0.01). CONCLUSION: This study indicates that baroreflex stimulation and hypoxia may be involved in the bi-phasic HR response of BHDs and thus in their longer apnea duration.

Apnea-induced changes in time estimation and its relation to bradycardia.

INTRODUCTION: Both exercise and hypoxia affect human ability to estimate time, an alteration thought to be induced by changes in subjects' level of arousal. Apnea induces cardiovascular changes and a decrease in oxygen uptake that indicate changes in physiological arousal. We tested time estimation (TE) during brief periods of voluntary apnea. We hypothesized that there would be a relationship between TE and heart rate (HR), a physiological indicator of arousal. METHODS: Subjects were two different groups of seven triathletes. To measure TE, the target time interval (20 or 30 s) was demonstrated and the subject was then asked to reproduce it under various conditions. Experiment 1 required 1 min of breath-holding while immersed in a pool at 31 degrees C. Experiment 2 was performed seated on a cycle ergometer in a laboratory and involved short periods of apnea at rest and during exercise. RESULTS: TE during apnea was significantly greater than baseline during both immersion and at rest on the cycle (+27% and +17% compared with their respective baselines). A significant linear negative correlation was demonstrated between TE and HR. Training in apnea during exercise had no effect on TE. DISCUSSION: Although this study revealed a relationship between TE and HR, our results should be interpreted with caution. Further studies are needed to confirm the relationship between HR and TE. A misperception of elapsed time may be a contributing factor in diving accidents which involve inexperienced breath-hold divers.