Objectives: The Sherpa ethnic group living at altitude in Nepal may have experienced natural selection in response to chronic hypoxia. We have previously shown that Sherpa in Kathmandu (1400 m) possess larger spleens and a greater apnea-induced splenic contraction compared to lowland Nepalis. This may be significant for exercise capacity at altitude as the human spleen responds to stress-induced catecholamine secretion by an immediate contraction, which results in transiently elevated hemoglobin concentration ([Hb]). Methods: To investigate splenic contraction in response to exercise at high-altitude (4300 m; Pb = ~450 Torr), we recruited 63 acclimatized Sherpa (29F) and 14 Nepali non-Sherpa (7F). Spleen volume was measured before and after maximal exercise on a cycle ergometer by ultrasonography, along with [Hb] and oxygen saturation (SpO2). Results: Resting spleen volume was larger in the Sherpa compared with Nepali non-Sherpa (237 ± 62 vs. 165 ± 34 mL, p <.001), as was the exercise-induced splenic contraction (Δspleen volume, 91 ± 40 vs. 38 ± 32 mL, p <.001). From rest to exercise, [Hb] increased (1.2 to 1.4 g.dl−1), SpO2 decreased (~9%) and calculated arterial oxygen content (CaO2) remained stable, but there were no significant differences between groups. In Sherpa, both resting spleen volume and the Δspleen volume were modest positive predictors of the change (Δ) in [Hb] and CaO2 with exercise (p-values from.026 to.037 and R2 values from 0.059 to 0.067 for the predictor variable). Conclusions: Larger spleens and greater splenic contraction may be an adaptive characteristic of Nepali Sherpa to increase CaO2 during exercise at altitude, but the direct link between spleen size/function and hypoxia tolerance remains unclear. 

Bergsbestigare - precis som fridykare - utsätts för syrebrist. Vid fridykning leder dykresponsen till minskad syreförbrukning, och mjältkontraktion ökar koncentrationen av cirkulerande hemoglobin (Hb), vilket försvarar kroppen mot syrebrist. Det är okänt om dessa försvarsreaktioner relaterar till de reaktioner som framkallas på hög höjd och vilken roll mjälten har på hög höjd. Min avhandling syftade till att undersöka om det finns något samband mellan dessa apné-inducerade reaktioner och tolerans mot hög höjd. I fem studier undersökte jag dykresponsen och mjältkontraktionen vid apné (anhållning), i olika grupper, inklusive fritidsvandrare, elitklättrare, inhemska sherpa (uppdelat mellan de som bor högt och de som bor lågt) och uthållighetsidrottare, på låg höjd och på hög höjd. Mitt primära fynd var slående: dykresponsen och mjältstorleken var associerade med tolerans mot syrebrist på hög höjd; lågländare med stark dykrespons och stor mjälte visade mindre symtom på akut hög höjdsjuka på hög höjd. Jag fann också att grupper som ofta exponeras för hög höjd har större mjälte jämfört med grupper som bor på havsnivå. Intressant nog hade Sherpa som bodde på hög höjd större mjältar jämfört med Sherpa som har migrerat till låg höjd. Ett annat viktigt fynd var att mjälten minskar i storlek med ~14% per 1000 m stigning hos lågländare, vilket var associerat med vilo- Hb. Jag fann också att uthållighetsidrottare, som är beroende av effektiv syretillförsel, har större mjältar jämfört med otränade individer. Jag drar slutsatsen att en stark dykrespons och en stor mjälte kan vara egenskaper hos höghöjdstoleranta lågländare som möjligen kan användas för att förutsäga höghöjdskänslighet. Studier 1–4 visade att mjälten är fördelaktig för att tolerera syrebrist på hög höjd i en rad olika grupper på hög höjd, troligen genom dess förmåga att reglera cirkulerande Hb. Sherpa hade större mjältar jämfört med lågländare, vilket tyder på att genetiska faktorer påverkar mjältstorleken, medan upptäckten att Sherpa som lever högt hade större mjältar än sherpa som lever lågt visar att mjältstorleken även bestäms av miljömässiga faktorer. Studie 4 visade en tonisk mjältkontraktion hos lågländare på hög höjd, vilket tyder på att den Hb-reglerande funktionen kan vara viktig innan EPO-inducerad ökning av röda blodkroppar sker, vilket kan bidra till individuell acklimatisering.

Voluntary apnea causes splenic contraction and reductions in heart rate (HR; bradycardia), and subsequent transient increases in hemoglobin concentration ([Hb]). Ascent to high altitude (HA) induces systemic hypoxia and reductions in oxygen saturation (SpO2 ), which may cause tonic splenic contraction, which may contribute to hematological acclimatization associated with HA ascent. We measured resting cardiorespiratory variables (HR, SpO2 , [Hb]) and resting splenic volume (via ultrasound) during incremental ascent from 1400 m (day 0), to 3440 m (day 3), 4240 m (day 7), and 5160 m (day 10) in non-acclimatized native lowlanders during assent to HA in the Nepal Himalaya. In addition, apnea-induced responses in HR, SpO2 and splenic volume were measured before and after two separate voluntary maximal apneas (A1-A2) at 1400 m, 3440 m and 4240 m. Resting spleen volume decreased -14.3% (-15.2 mL)/1000 m with ascent, from 140±41 mL (1400 m), to 108±28 mL (3440 m; P > 0.99), 94±22 mL (4240 m; P = 0.009) and 84±28 mL (5160 m; P = 0.029), with concomitant increases in [Hb] from 125±18.3 g/L (1400 m) to 128±10.4 g/L (3440 m), 138.8±12.7 g/L (4240 m) and 157.5±8 g/L (5160 m; P = 0.021). Apnea-induced splenic contraction was 50±15 mL (1400 m), 44±17 mL (3440 m; P > 0.99) and 26±8 mL (4240 m; P = 0.002), but was not consistently associated with increases in [Hb]. The apnea-induced bradycardia was more pronounced at 3440 m (A1:P = 0.04; A2:P = 0.094) and at 4240 m (A1:P = 0.037 A2:P = 0.006) compared to values at 1400 m. We conclude that hypoxia-induced splenic contraction at rest (a) may contribute to restoring arterial oxygen content through its [Hb]-enhancing contractile function and (b) eliminates further apnea-induced [Hb] increases in hypoxia. We suggest that tonic splenic contraction may contribute to hematological acclimatization early in HA ascent in humans.

The human spleen contracts in response to stress-induced catecholamine secretion, resulting in a temporary rise in haemoglobin concentration ([Hb]). Recent findings highlighted enhanced splenic response to exercise at high altitude in Sherpa, possibly due to a blunted splenic response to hypoxia. To explore the potential blunted splenic contraction in Sherpas at high altitude, we examined changes in spleen volume during hyperoxic breathing, comparing acclimatized Sherpa with acclimatized individuals of lowland ancestry. Our study included 14 non-Sherpa (7 female) residing at altitude for a mean continuous duration of 3 months and 46 Sherpa (24 female) with an average of 4 years altitude exposure. Participants underwent a hyperoxic breathing test at altitude (4300 m; barrometric pressure = ∼430 torr; (Formula presented.) = ∼90 torr). Throughout the test, we measured spleen volume using ultrasonography and monitored oxygen saturation ((Formula presented.)). During rest, Sherpa exhibited larger spleens (226 ± 70 mL) compared to non-Sherpa (165 ± 34 mL; P < 0.001; effect size (ES) = 0.95, 95% CI: 0.3–1.6). In response to hyperoxia, non-Sherpa demonstrated 22 ± 12% increase in spleen size (35 ± 17 mL, 95% CI: 20.7–48.9; P < 0.001; ES = 1.8, 95% CI: 0.93–2.66), while spleen size remained unchanged in Sherpa (−2 ± 13 mL, 95% CI: −2.4 to 7.3; P = 0.640; ES = 0.18, 95% CI: −0.10 to 0.47). Our findings suggest that Sherpa and non-Sherpas of lowland ancestry exhibit distinct variations in spleen volume during hyperoxia at high altitude, potentially indicating two distinct splenic functions. In Sherpa, this phenomenon may signify a diminished splenic response to altitude-related hypoxia at rest, potentially contributing to enhanced splenic contractions during physical stress. Conversely, non-Sherpa experienced a transient increase in spleen size during hyperoxia, indicating an active tonic contraction, which may influence early altitude acclimatization in lowlanders by raising [Hb]. 

Splenic contraction, which leads to ejection of stored erythrocytes, is greater in athletes involved in regular freediving or high-altitude activities. As this response facilitates oxygen-carrying capacity, similar characteristics may be expected of elite endurance athletes. Therefore, our aims were to compare resting and apnea-induced splenic volume in endurance athletes and untrained individuals, and to assess the athletes' exercise-induced splenic volume. Twelve elite biathletes (7 women) and 12 controls (6 women) performed a maximal effort apnea in a seated position. In addition, the biathletes completed a maximal roller-skiing time trial. Splenic dimensions were measured by ultrasonic imaging for subsequent volume calculations, whereas Hb was analyzed from capillary blood samples and cardiorespiratory variables were monitored continuously. Baseline splenic volume was larger in the biathletes (214 +/- 56 mL) compared with controls (157 +/- 39 mL, P = 0.008) and apnea-induced splenic contraction was also greater in the biathletes (46 +/- 20 mL vs. 30 +/- 16 mL, P = 0.035). Hb increased immediately after apnea in the biathletes (4.5 +/- 4.8%, P = 0.029) but not in the controls (-0.7 +/- 3.1%, P = 0.999). Increases in exercise-induced splenic contraction (P = 0.008) and Hb (P = 0.001) were greater compared with the apnea-induced responses among the athletes. Baseline splenic volume tended to be correlated with <(V)over dot>o(2max) (r= 0.584, P = 0.059). We conclude that elite biathletes have greater splenic volume with a greater ability to contract and elevate Hb compared with untrained individuals. These characteristics may transiently enhance O-2-carrying capacity and possibly increase O-2 uptake, thereby helping biathletes to cope with high intermittent O-2 demands and severe O-2 deficits that occur during biathlon training and competition. NEW & NOTEWORTHY This study demonstrates that elite biathletes have larger splenic volume, apnea-induced splenic contraction, and Hb elevation compared with untrained individuals, which is likely functional to cope with high O-2 demands and substantial O-2 deficits. We believe that enhanced splenic contraction may be of importance during competitions involving crosscountry skiing, to regulate circulating Hb and enhance O-2-carrying capacity, which may protect Ca-O2, and increase O-2 uptake.

Acute mountain sickness (AMS) is a potentially life-threatening illness that may develop during exposure to hypoxia at high altitude (HA). Susceptibility to AMS is highly individual, and the ability to predict it is limited. Apneic diving also induces hypoxia, and we aimed to investigate whether protective physiological responses, i.e., the cardiovascular diving response and spleen contraction, induced during apnea at low-altitude could predict individual susceptibility to AMS. Eighteen participants (eight females) performed three static apneas in air, the first at a fixed limit of 60 s (A1) and two of maximal duration (A2-A3), spaced by 2 min, while SaO(2), heart rate (HR) and spleen volume were measured continuously. Tests were conducted in Kathmandu (1470 m) before a 14 day trek to mount Everest Base Camp (5360 m). During the trek, participants reported AMS symptoms daily using the Lake Louise Questionnaire (LLQ). The apnea-induced HR-reduction (diving bradycardia) was negatively correlated with the accumulated LLQ score in A1 (r(s) = -0.628, p= 0.005) and A3 (r(s) = -0.488, p = 0.040) and positively correlated with SaO(2) at 4410 m (A1: r = 0.655, p = 0.003; A2: r = 0.471, p = 0.049; A3: r = 0.635, p = 0.005). Baseline spleen volume correlated negatively with LLQ score (r(s) = -0.479, p = 0.044), but no correlation was found between apnea-induced spleen volume reduction with LLQ score (r(s) = 0.350, p = 0.155). The association between the diving bradycardia and spleen size with AMS symptoms suggests links between physiological responses to HA and apnea. Measuring individual responses to apnea at sea-level could provide means to predict AMS susceptibility prior to ascent.

High-altitude (HA) natives have evolved some beneficial responses leading to superior work capacity at HA compared to native lowlanders. Our aim was to study two responses potentially protective against hypoxia: the spleen contraction elevating hemoglobin concentration (Hb) and the cardiovascular diving response in Sherpa highlanders, compared to lowlanders. Male participants were recruited from three groups: (1) 21 Sherpa living at HA (SH); (2) seven Sherpa living at low altitude (SL); and (3) ten native Nepalese lowlanders (NL). They performed three apneas spaced by a two-min rest at low altitude (1370 m). Their peripheral oxygen saturation (SpO(2)), heart rate (HR), and spleen volume were measured across the apnea protocol. Spleen volume at rest was 198 +/- 56 mL in SH and 159 +/- 35 mL in SL (p= 0.047). The spleen was larger in Sherpa groups compared to the 129 +/- 22 mL in NL (p< 0.001 compared to SH;p= 0.046 compared to SL). Spleen contraction occurred in all groups during apnea, but it was greater in Sherpa groups compared to NL (p< 0.001). HR was lower in Sherpa groups compared to NL both during rest (SL:p< 0.001; SH:p= 0.003) and during maximal apneas (SL:p< 0.001; SH:p= 0.06). The apnea-induced HR reduction was 8 +/- 8% in SH, 10 +/- 4% in SL (NS), and 18 +/- 6% in NL (SH:p= 0.005; SL:p= 0.021 compared to NL). Resting SpO(2)was similar in all groups. The progressively decreasing baseline spleen size across SH, SL, and NL suggests a role of the spleen at HA and further that both genetic predisposition and environmental exposure determine human spleen size. The similar HR responses of SH and SL suggest that a genetic component is involved in determining the cardiovascular diving response.

While MRI and CT are the gold standards for assessments of splenic size in clinical settings, ultrasonography is particularly suited due to its portability, cost efficiency and easy utilization. However, ultrasonography is associated with subjective assessment, potentially resulting in increased variation. We used a test–retest design aiming to determine the reliability of splenic measurements assessed by ultrasonography during apnea. In addition, we compared reliability between different equations for volume calculations: Koga, Prolate ellipsoid and Pilström. Twelve healthy participants (6 women) performed two tests separated by 15 min, comprising a maximal voluntary apnea in a seated position. Splenic dimensions were measured via ultrasonography for 5 min before and immediately following apnea. Resting splenic volume displayed high test–retest reliability between tests (Pilström: 157 ± 39 mL vs 156 ± 34 mL, p = .651, ICC = .970, p < .001, CV = 2.98 ± 0.1%; Prolate ellipsoid: 154 ± 37 mL vs 144 ± 43 mL, p = .122, ICC = .942, p < .001, CV = 5.47 ± 0.3%; Koga: 142 ± 37 mL vs 140 ± 59 mL, p = .845, ICC = .859, p < .001, CV = 9.72 ± 1.4%). Apnea-induced volumes displayed similar reliability (127 ± 29 mL vs 129 ± 28 mL, p = .359, ICC = .967, p < .001, CV = 3.14 ± 3.1%). Reliability was also high between equations (Pilström vs Prolate ellipsoid: ICC = .818, p < .001, CV = 7.33 ± 0.3%, bias =  − 3.1 mL, LoA =  − 46.9 to 40.7 mL; Pilström vs Koga: ICC = .618, p < .01, CV = 11.83 ± 1.1%, bias =  − 14.8 mL, LoA =  − 76.9 to 47.3 mL). We conclude that splenic ultrasonographic measurements have practical applications during laboratory and field-based research as a reliable method detecting splenic volume change consistently between repeated tests. The Pilström equation displayed similar reliability compared to the prolate ellipsoid formula and slightly higher compared to the Koga formula and may be particularly useful to account for individual differences in splenic dimensions.

The human spleen acts as a reservoir for red blood cells, which is mobilized into the systemic circulation during various conditions such as hypoxia and physical exertion. Cross-country (XC) skiers, renowned for their exceptional aerobic capacity, are regularly exposed to high-intensity exercise and local oxygen deficits. We investigated a putative dose-dependent relationship between splenic contraction and concomitant hemoglobin concentration ([Hb]) elevation across four exercise intensities in well-trained XC skiers. Fourteen male XC skiers voluntarily participated in a 2-day protocol, encompassing a serial apnea test and a VO2max test (day 1), followed by three submaximal exercise intensities on a roller skiing treadmill corresponding to 55, 70, and 85% of VO2max (day 2). Spleen volume was measured via ultrasonic imaging, and venous blood samples were used to determine [Hb] levels. Baseline spleen volume was similar (266(35) mL) for all conditions (NS). Notably, all conditions induced significant splenic contractions and transient [Hb] elevations. The VO2max test exhibited the most pronounced splenic contraction (35.8%, p < 0.001) and a [Hb] increase of 8.1%, while the 85% exercise intensity led to 27.1% contraction and the greatest [Hb] increase (8.3%, < 0.001) compared to baseline. The apnea test induced relatively smaller responses (splenic contraction: 20.4%, [Hb] = 3.3%, p < 0.001), akin to the response observed at the 70% exercise intensity (splenic contraction = 23%, [Hb] = 6.4%, p < 0,001) and 55% (splenic contraction = 20.0%, [Hb] = 4.8%, p < 0.001). This study shows a discernible dose-dependent relationship between splenic contraction and [Hb] increase with levels of exercise, effectively distinguishing between submaximal and maximal exercise intensity.

Purpose: Splenic contraction increases circulating hemoglobin (Hb) with advantages during hypoxia. As both hypoxia and exercise have been shown to be important separate triggers of splenic contraction we aimed to investigate if the spleen response to simulated high altitude (HA) is enhanced by superimposing exercise. Method: Fourteen healthy volunteers (seven females) performed the following protocol in a normobaric environment sitting on an ergometer cycle: 20 min rest in normoxia; 20 min rest while breathing hypoxic gas simulating an altitude of 3500 m; 10 min exercise at an individually set intensity while breathing the hypoxic gas; 20 min rest in hypoxia; and finally 20 min rest in normoxia. Spleen measurements were collected by ultrasonic imaging and venous Hb measured at the end of each intervention. Result: Mean ± SD baseline spleen volume during normoxic rest was 280 ± 107 mL, the volume was reduced by 22% during rest in hypoxia to 217 ± 92 mL (p < 0.001) and by 33% during exercise in hypoxia (189 mL; p < 0.001). Hb was 140.7 ± 7.0 g/L during normoxic rest and 141.3 ± 7.4 g/L during hypoxic rest (NS), but increased by 5.3% during hypoxic exercise (148.6 ± 6.3 g/L; p < 0.001). Spleen volume and Hb were stepwise changed back to baseline at cessation of exercise and return to normoxia. Conclusion: Splenic contraction is induced by hypoxia and further enhanced by superimposing exercise, and reduced when exercise ceases, in a step-wise manner, showing that the tonic but partial contraction observed in long-term field expeditions to HA may occur also in the short term. This “graded response” may be beneficial during acclimatization to HA, to cope with moderate chronic hypoxia during rest while allowing additional enhancement of oxygen carrying capacity to overcome short bouts of extreme hypoxia caused by exercise. 

BACKGROUND: Apnea training enhances bradycardia and improves competitive apnea performance, and has been proposed as a training method for other sports, such as swimming. We evaluated the effects of apneic underwater swimming, i.e. dynamic apnea (DYN), in 9 competitive swimmers (TR) who completed ten DYN sessions over 2 weeks.

METHODS: TR performed pre- and post-training tests including a static apnea test with continuous heart rate (HR) and peripheral oxygen saturation measurements, all-out 50m and 100m freestyle tests and an all-out DYN test. Control groups were competitive swimmers (SC; n=10) that trained swimming without DYN, and a non-swimmer group (AC; n=10) performing only static apnea tests.

RESULTS: Post-training, TR mean±SD time for 50m freestyle improved from 25.51±2.01s to 24.64±2.02s (p<0.01) and for 100m from 55.5±4.2s to 54.1±4.4s (p<0.05). SC also improved their 100m time from 56.7±3.3s to 56.0±3.1s (p<0.01; p=0.07 between groups). Only TR performed DYN tests; DYN distance increased from 62.1±11.5m to 70.9±18.9m (p<0.05) while DYN speed decreased from 0.74±0.14m/s to 0.64±0.18m/s (p<0.01). Static apnea duration did not change in any of the groups, but HR-reduction was enhanced posttraining only in TR (24.8±14.8% to 31.1±10.9%, p<0.01; p<0.001 between groups).

CONCLUSIONS: We conclude that 2 weeks of DYN training enhanced DYN performance, which may be caused by the enhanced apnea-induced diving bradycardia. Further research is required to determine whether DYN training enhances short distance freestyle swimming performance.

Purpose

Hyperventilation is considered a major risk factor for hypoxic blackout during breath-hold diving, as it delays the apnea breaking point. However, little is known about how it affects oxygenation, the diving response, and spleen contraction during serial breath-holding.

Methods

18 volunteers with little or no experience in freediving performed two series of 5 apneas with cold facial immersion to maximal duration at 2-min intervals. In one series, apnea was preceded by normal breathing and in the other by 15 s of hyperventilation. End-tidal oxygen and end-tidal carbon dioxide were measured before and after every apnea, and peripheral oxygen saturation, heart rate, breathing movements, and skin blood flow were measured continuously. Spleen dimensions were measured every 15 s.

Results

Apnea duration was longer after hyperventilation (133 vs 111 s). Hyperventilation reduced pre-apnea end-tidal CO2 (17.4 vs 29.0 mmHg) and post-apnea end-tidal CO2 (38.5 vs 40.3 mmHg), and delayed onset of involuntary breathing movements (112 vs 89 s). End-tidal O2 after apnea was lower in the hyperventilation trial (83.4 vs 89.4 mmHg) and so was the peripheral oxygen saturation nadir after apnea (90.6 vs 93.6%). During hyperventilation, the nadir peripheral oxygen saturation was lower in the last apnea than in the first (94.0% vs 86.7%). There were no differences in diving response or spleen volume reduction between conditions or across series.

Conclusions

Serial apneas  revealed a previously undescribed aspect of hyperventilation; a progressively increased desaturation across the series, not observed after normal breathing and could heighten the risk of a blackout.

The human spleen can contract and transiently boost the blood with stored erythrocytes. We measured spleen volume and contraction during apneas in two groups, each containing 12 Caucasian participants (each 3 women): one group planning to summit Mt. Everest (8848 m; "Climbers") and another trekking to Everest Base Camp (5300 m; "Trekkers"). Tests were done in Kathmandu (1370 m) 1-3 days after arrival, before the Climb/Trek. Age, height, weight, vital capacity, resting heart rate, and arterial oxygen saturation were similar between groups (not significant). After 15 minutes of sitting rest, all participants performed a 1-minute apnea and, after 2 minutes of rest, 1 maximal duration apnea was performed. Six of the climbers did a third apnea and hemoglobin concentration (Hb) was measured. Three axial spleen diameters were measured by ultrasonic imaging before and after the apneas for spleen volume calculation. Mean (standard deviation) baseline spleen volume was larger in Climbers [367 (181) mL] than in Trekkers [228 (70) mL; p = 0.022]. Spleen contraction occurred during apneas in both groups, with about twice the magnitude in Climbers. Three apneas in six of the Climbers resulted in a spleen volume reduction from 348 (145) to 202 (91) mL (p = 0.005) and an Hb elevation from 147.9 (13.1) to 153.3 (11.3) g/L (p = 0.024). Maximal apneic duration was longer in Climbers [88 (23) seconds vs. 67 (18) seconds in Trekkers; p = 0.023]. We concluded that a large spleen characterizes Climbers, suggesting that spleen function may be important for high-altitude climbing performance.