Geschlechts- und trainingsabhängige Effekte in der Variabilität der Sauerstoffaffinität zum Hämoglobin

Einleitung: Hypoxie, definiert als ein Mangel an Sauerstoff (O2), ist bei zahlreichen Pathologien von entscheidender Bedeutung. Die Hämoglobin-O2-Affinität, repräsentiert durch den p50 (O2-Partialdruck bei 50 % O2-Sättigung), ist ein für die Gewebeoxygenierung hochgradig relevanter Faktor, der im klinischen Alltag nur selten berücksichtigt wird. Methoden: 60 junge gesunde Frauen und Männer (jeweils zur Hälfte trainiert, zur anderen Hälfte untrainiert) wurden einem Leistungstest zur Bestimmung der maximalen Sauerstoffaufnahmekapazität (VO2max) nach erweitertem Bruce-Protokoll unterzogen. Venöses und kapilläres Blut wurde mittels Blutgasanalyse (BGA) vor und nach dem Test untersucht. Venöse Blutproben wurden weiterhin mittels Tonometrie zur Erstellung von O2-Bindungskurven verwendet. Des Weiteren wurden die 2,3-Bisphosphoglycerat- sowie die Bisphosphoglyceratmutase-Quantität im Blut bestimmt und eine bioelektrische Impendanzmessung zur Bestimmung der Körperzusammensetzung durchgeführt. Ergebnisse: Sowohl die VO2max als auch die Körperzusammensetzung der Versuchspersonen lagen im erwarteten Bereich und bestätigten die adäquate Zuordnung der Versuchspersonen in die Gruppen. Es konnte keine trainingsabhängige Veränderung der Hämoglobin-O2-Affinität festgestellt werden. Demgegenüber wurden deutliche geschlechtsabhängige Unterschiede der O2-Abgabefähigkeit per se festgestellt. Der tonometrisch bestimmte p50 der Probandinnen lag in Ruhe mit durchschnittlich 25,09 ± 0,97 mmHg signifikant höher als bei den Männern mit 23,7 ± 0,9 mmHg. Hiermit korrelierend war bei den Probandinnen auch die 2,3-Bisphosphoglycerat-Konzentration pro Hämoglobin sowie die Bisphosphoglyceratmutase-Konzentration erhöht. Nach absolviertem Ausbelastungstest erhöhte sich der p50 bei den Männern stärker als bei den Frauen, sodass der p50 nach Belastung bei 30,13 ± 2,04 mmHg ohne Unterschiede zwischen den Gruppen lag. Unabhängig davon zeigte sich eine unerwartet hohe Diversität der individuellen Hämoglobin-O2-Affinität. Der in der BGA kalkulierte p50 Wert aus venösen Proben korrelierte im Gegensatz zu den kapillären Proben gut mit den tonometrisch erhobenen p50 Werten. Diskussion: Entgegen der aktuellen Sichtweise konnten wir keinen Trainingseinfluss auf die Hämoglobin-O2-Affinität nachweisen, jedoch zeigte sich ein deutlicher Geschlechterunterschied. Die bessere Abgabefähigkeit von Sauerstoff an das Gewebe bei Frauen wird bei Männern vermutlich durch eine kompensatorisch erhöhte Hämoglobinkonzentration ausgeglichen. Die in dieser Studie gezeigten großen Unterschiede der O2-Abgabefähigkeit innerhalb einer gesunden Kohorte (∆p50in Ruhe ~7 mmHg) lassen vermuten, dass es auch bei hospitalisierten Patientinnen und Patienten ein weites Spektrum gibt, welches therapeutisch unbedingt beachtet werden sollte. Weitere Studien sind dringend nötig, um die individuelle Hämoglobin-O2-Affinität im Kontext verschiedener Pathologien mit resultierender Gewebehypoxie einschätzen zu können. Der Einsatz von neuartigen Substanzen zur Modulation der Hämoglobin-O2-Affinität könnte erheblich zur personalisierten Therapie beitragen. Für die klinisch relevante Abschätzung der Hämoglobin-O2-Affinität aus einer einzelnen Blutprobe mittels BGA, sind venöse, jedoch nicht kapilläre Proben geeignet.Introduction: Hypoxia, a condition of inadequate oxygen supply, plays a central role in numerous pathologies. The oxygen affinity to hemoglobin, as indicated by the p50 value, finally determines the grade of tissue oxygenation and is currently often neglected in clinical practice. Methods: We collected data concerning oxygen release in 60 young and healthy volunteers (both sexes, either endurance trained or untrained) before and after a VO2max test, which has been performed according to an extended Bruce protocol. Blood gas analysis (BGA) of venous and capillary probes were obtained before and after the test. Venous blood samples served for determination of oxygen dissociation curves (ODC) using tonometry. Furthermore, 2,3-bisphoglycerate and bisphospholycerate mutase (BPGM) levels were measured. Bioelectrical impedance analysis was carried out to determine body composition. Results: VO2max (maximal oxygen consumption per minute per kilogram body weight) and body composition were as expected, confirming adequate allocation of the volunteers into groups. No training-dependent changes in hemoglobin-O2-affinity could be detected. In contrast, significant sex-dependent differences in hemoglobin-O2-affinity at rest were found. Female p50 (25,09 ± 0,97 mmHg) indicated lower hemoglobin-O2-affinity compared to men (p50: 23,7 ± 0,9 mmHg). In line, the 2,3-bisphosphoglycerate concentration per hemoglobin and the BPGM protein level were also elevated in women compared to men. However, after VO2max test increased p50 values of women and men reached similar end points. While calculated p50c values of venous BGAs show comparable results with p50 values obtained by ODC, the estimated p50e of the capillary samples does not correlate with the tonometric results. The hemoglobin-O2-affinity showed an unexpected diversity among individuals. Discussion: In contrast to current perception, we found no difference of hemoglobin-O2-affinity as a result of regular endurance exercise. Notably, we observed a significant sex dependent difference, indicating women having lower hemoglobin-O2-affinity compared to men and thus, more easily release oxygen to the tissue. Men seem to compensate higher hemoglobin-O2-affinity by elevated hemoglobin levels to ensure sufficient tissue oxygen availability. The broad diversity in hemoglobin-O2-affinity within a healthy cohort (at rest ~7 mmHg) suggest that there is also a wide range in hospitalized patients. Individual differences of tissue oxygen availability need to be considered for individualized therapy. Future studies need to assess the effects of substances already used to modulate the p50. For clinical praxis, we can recommend calculated p50 values from venous, but not capillary blood samples

The relevance of body composition assessment for the rating of perceived exertion in trained and untrained women and men

Introduction: Mechanic power output (MPO) and oxygen consumption (VO2) reflect endurance capacity and are often stated relative to body mass (BM) but less often per skeletal muscle mass (SMM). Rating of perceived exertion (RPE) has previously shown conflicting results between sexes at submaximal intensities. Individual body composition, however, largely differs due to sex and training status. It was the aim of this study to evaluate RPE of untrained and trained individuals of both sexes considering body composition and to estimate whether RPE could be improved as a tool to determine endurance capacity. Methods: The study included 34 untrained adults (age 26.18 ± 6.34 years, 18 women) and 29 endurance trained (age 27.86 ± 5.19, 14 women) who were measured for body composition (InBody 770, InBody Europe B.V., Germany) and tested on a treadmill (Pulsar, H/P/Cosmos, Germany) for aerobic capacity (Metalyzer 3B, Cortex Biophysik GmbH, Germany) in an all-out exercise test applying the Bruce-protocol. VO2, MPO, heart rate (HR), and RPE were obtained at each exercise stage. VO2 and MPO were calculated per BM and SMM. RPE values were correlated with absolute VO2 and MPO, as well as relative to BM, and SMM. HR values and the parameters’ standardized values served for comparison to standard procedures. Results: VO2 and MPO were higher in men compared to women and in trained compared to untrained participants. No differences between groups and sexes exist when VO2 and MPO were calculated per BM. When calculated per SMM, VO2 and MPO indicate opposite results already at low intensity stages of exercise test. RPE values had highest correlation with MPO per SMM (R2 = 0.8345) compared to absolute MPO (R2 = 0.7609), or MPO per BM (R2 = 0.8176). Agreement between RPE and MPO per SMM was greater than between RPE and HR (p = 0.008). Conclusion: Although RPE represents a subjective value at first glance, it was shown that RPE constitutes a valuable tool to estimate endurance capacity, which can be further enhanced if individual body composition is considered. Furthermore, MPO and VO2 should be considered relative to SMM. These findings might help to avoid over-exertion, especially among untrained people, by adjusting the training intensity for each subject according to the individual strain evaluated in an exercise test based on individual body composition

The Association of Fatigue With Decreasing Regularity of Locomotion During an Incremental Test in Trained and Untrained Healthy Adults

Fatigue is a key factor that affects human motion and modulates physiology, biochemistry, and performance. Prolonged cyclic human movements (locomotion primarily) are characterized by a regular pattern, and this extended activity can induce fatigue. However, the relationship between fatigue and regularity has not yet been extensively studied. Wearable sensor methodologies can be used to monitor regularity during standardized treadmill tests (e.g., the widely used Bruce test) and to verify the effects of fatigue on locomotion regularity. Our study on 50 healthy adults [27 males and 23 females; <40 years; five dropouts; and 22 trained (T) and 23 untrained (U) subjects] showed how locomotion regularity follows a parabolic profile during the incremental test, without exception. At the beginning of the trial, increased walking speed in the absence of fatigue is associated with increased regularity (regularity index, RI, a. u., null/unity value for aperiodic/periodic patterns) up until a peak value (RI = 0.909 after 13.8 min for T and RI = 0.915 after 13.4 min for U subjects; median values, n. s.) and which is then generally followed (after 2.8 and 2.5 min, respectively, for T/U, n. s.) by the walk-to-run transition (at 12.1 min for both T and U, n. s.). Regularity then decreases with increased speed/slope/fatigue. The effect of being trained was associated with significantly higher initial regularity [0.845 (T) vs 0.810 (U), p < 0.05 corrected], longer test endurance [23.0 min (T) vs 18.6 min (U)], and prolonged decay of locomotor regularity [8.6 min (T) vs 6.5 min (U)]. In conclusion, the monitoring of locomotion regularity can be applied to the Bruce test, resulting in a consistent time profile. There is evidence of a progressive decrease in regularity following the walk-to-run transition, and these features unveil significant differences among healthy trained and untrained adult subjects

A broad diversity in oxygen affinity to haemoglobin

Oxygen affinity to haemoglobin is indicated by the p50 value (pO2 at 50% O2Hb) and critically determines cellular oxygen availability. Although high Hb-O2 affinity can cause tissue hypoxia under conditions of well O2 saturated blood, individual differences in p50 are commonly not considered in clinical routine. Here, we investigated the diversity in Hb-O2 affinity in the context of physiological relevance. Oxyhaemoglobin dissociation curves (ODCs) of 60 volunteers (18–40 years, both sexes, either endurance trained or untrained) were measured at rest and after maximum exercise (VO2max) test. At rest, p50 values of all participants ranged over 7 mmHg. For comparison, right shift of ODC after VO2max test, representing the maximal physiological range to release oxygen to the tissue, indicated a p50 difference of up to 10 mmHg. P50 at rest differs significantly between women and men, with women showing lower Hb-O2 affinity that is determined by higher 2,3-BPG and BPGM levels. Regular endurance exercise did not alter baseline Hb-O2 affinity. Thus, p50 diversity is already high at baseline level and needs to be considered under conditions of impaired tissue oxygenation. For fast prediction of Hb-O2 affinity by blood gas analysis, only venous but not capillary blood samples can be recommended