Impact of a single blood donation on hemoglobin mass, iron stores, and maximum oxygen uptake in pre-menopausal women-A pilot study.

BACKGROUND: During whole blood donation (BD), 500 mL of blood is drawn. The time interval between two BDs is at least 8-12 weeks. This period might be insufficient for restoring hemoglobin mass (Hbmass) and iron especially in women, who generally have lower Hbmass and iron availability. Since both variables influence physical performance, this pilot study aimed to monitor Hbmass, iron status, and maximum oxygen uptake (V̇O2max) recovery in women after a single BD. STUDY DESIGN AND METHODS: In 10 women (24.7 ± 1.7 years), Hbmass, hemoglobin concentration [Hb], iron status, and V̇O2max were assessed before and up to 12 weeks after a single BD. RESULTS: BD reduced Hbmass from 562 ± 70 g to 499 ± 64 g (p < .001). Although after 8 weeks no significant mean difference was detected, 7 women had not returned to baseline after 12 weeks. [Hb] did not return to initial values (13.4 ± 0.7 g/dL) after 12 weeks (12.9 ± 0.7 g/dL, p < .01). Ferritin decreased from baseline until week 6 (40.9 ± 34.2 ng/mL vs. 12.1 ± 6.9 ng/mL, p < .05) and was not restored after 12 weeks (18.4 ± 12.7 ng/mL, p < .05), with 6 out of 10 women exhibiting iron deficiency (ferritin <15 ng/mL). V̇O2max was reduced by 213 ± 47 mL/min (7.2 ± 1.2%; p < .001) and remained below baseline after 12 weeks (3.2 ± 1.4%, p < .01). DISCUSSION: For most pre-menopausal women, 12 weeks were not sufficient to recover from BD and achieve baseline Hbmass and iron stores resulting in prolonged reduction of aerobic capacity. A subsequent BD might lead to a severe anemia.

The effect of posture and exercise on blood CO kinetics during the optimized carbon monoxide rebreathing procedure.

An indispensable precondition for the determination of hemoglobin mass (Hbmass) and blood volume by CO rebreathing is complete mixing of CO in the blood. The aim of this study was to demonstrate the kinetics of CO in capillary and venous blood in different body positions and during moderate exercise. Six young subjects (4 male, 2 female) performed three 2-min CO rebreathing tests in seated (SEA) & supine (SUP) positions as well as during moderate exercise (EX) on a bicycle ergometer. Before, during, and until 15 min after CO rebreathing cubital venous and capillary blood samples were collected simultaneously and COHb% was determined. COHb% kinetics were significantly slower in SEA than in SUP or EX. Identical COHb% in capillary and venous blood were reached in SEA after 5.0 ± 2.3 min, in SUP after 3.2 ± 1.3 min and in EX after 1.9 ± 1.2 min (EX vs. SEA p < .01, SUP vs. SEA p < .05). After 7th min, Hbmass did not differ between the resting positions (capillary: SEA 766 ± 217 g, SUP 761 ± 227 g; venous: SEA 759 ± 224 g, SUP 744 ± 207 g). Under exercise, however, a higher Hbmass (p < .05) was determined (capillary: 823 ± 221 g, venous: 804 ± 226 g). In blood, the CO mixing time in the supine position is significantly shorter than in the seated position. By the 6th minute complete mixing is achieved in either position giving similar Hbmass determinations. CO-rebreathing under exercise conditions, however, leads to ∼7% higher Hbmass values.

Quantification of testosterone-dependent erythropoiesis during male puberty.

NEW FINDINGS: What is the central question of this study? To what extent does testosterone influence haemoglobin formation during male puberty? What is the main finding and its importance? In boys, testosterone might be responsible for about 65% of the increase in haemoglobin mass during puberty. The underlying mechanisms are assumed to be twofold: (i) indirectly, mediated by the increase in lean body mass, and (ii) directly by immediate testosterone effects on erythropoiesis. Thereby, an increase in testosterone of 1 ng/ml is associated with an increase in haemoglobin mass of ∼65 g. These processes are likely to determine endurance performance in adulthood. ABSTRACT: The amount of haemoglobin during puberty is related to endurance performance in adulthood. During male puberty, testosterone stimulates erythropoiesis and could therefore be used as a marker for later endurance performance. This cross-sectional study aimed to determine the relationship between serum testosterone concentration and haemoglobin mass (Hbmass) in both male and female children and adolescents and to evaluate the possible influences of altitude and training. Three-hundred and thirteen differentially trained boys and girls aged from 9 to 18 years and living at altitudes of 1000 and 2600 m above sea level entered the study. The stage of sexual maturation was determined according to the classification of Tanner. Testosterone was measured by ELISA. Hbmass was determined by CO-rebreathing. Haemoglobin concentration did not change during maturation in girls and was 11% higher during puberty in boys, while Hbmass was elevated by 33% in Tanner stage V compared to stage II in girls (498 ± 77 vs. 373 ± 88 g) and by 95% in boys (832 ± 143 vs. 428 ± 95 g). This difference can most likely be attributed to indirect testosterone influences through an increase in lean body mass (LBM) and to direct testosterone effects on erythropoiesis, which increase the Hbmass by ∼65 g per 1 ng/ml. Altitude and training statuses were not associated with testosterone, but with an increase in Hbmass (altitude by 1.1 g/kg LBM, training by 0.8 g/kg LBM). Changes in Hbmass are closely related to testosterone levels during male puberty. Further studies will show whether testosterone and Hbmass during childhood and adolescence can be used as diagnostic tools for endurance talents.

A carbon monoxide 'single breath' method to measure total haemoglobin mass: a feasibility study.

NEW FINDINGS: What is the central question of this study? Is it possible to modify the CO-rebreathing method to acquire reliable measurements of haemoglobin mass in ventilated patients? What is the main finding and its importance? A 'single breath' of CO with a subsequent 30 s breath hold provides almost as exact a measure of haemoglobin mass as the established optimized CO-rebreathing method when applied to healthy subjects. The modified method has now to be checked in ventilated patients before it can be used to quantify the contributions of blood loss and of dilution to the severity of anaemia. ABSTRACT: Anaemia is defined by the concentration of haemoglobin (Hb). However, this value is dependent upon both the total circulating haemoglobin mass (tHb-mass) and the plasma volume (PV) - neither of which is routinely measured. Carbon monoxide (CO)-rebreathing methods have been successfully used to determine both PV and tHb-mass in various populations. However, these methods are not yet suitable for ventilated patients. This study aimed to modify the CO-rebreathing procedure such that a single inhalation of a CO bolus would enable its use in ventilated patients. Eleven healthy volunteers performed four CO-rebreathing tests in a randomized order, inhaling an identical CO volume. In two tests, CO was rebreathed for 2 min (optimized CO rebreathing; oCOR), and in the other two tests, a single inhalation of a CO bolus was conducted with a subsequent breath hold of 15 s (Procnew 15s) or 30 s (Procnew 30s). Subsequently, the CO volume in the exhaled air was continuously determined for 20 min. The amount of CO exhaled after 7 and 20 min was respectively 3.1 ± 0.3 and 5.9 ± 1.1 ml for oCOR, 8.7 ± 3.6 and 12.0 ± 4.4 ml for Procnew 15s and 5.1 ± 2.0 and 8.4 ±2.6 ml for Procnew 30s. tHb-mass was 843 ± 293 g determined by oCOR, 821 ± 288 g determined by Procnew 15s (difference: P < 0.05) and 849 ± 311 g determined by Procnew 30s. Bland-Altman plots demonstrated slightly lower tHb-mass values for Procnew 15s compared with oCOR (-21.8 ± 15.3 g) and similar values for Procnew 30s. In healthy volunteers, a single inhalation of a CO bolus, preferably followed by a 30 s breath hold, can be used to determine tHb-mass. These results must now be validated for ventilated patients.

Clinical importance of distinguishing true anemia from dilutional pseudo-anemia: Consequences of a 3-year follow-up volume assessment in a heart failure patient.

In chronic heart failure, dilutional anemia and hypervolemia may occur due to plasma volume expansion, the latter sometimes exacerbated by an increase in red cell volume. Diagnosis and a therapeutic strategy require determination of vascular volumes.

Stability of carboxy-hemoglobin during storage at different temperatures.

Accurate determination of carboxy-hemoglobin (COHb%) is essential for the assessment of hemoglobin mass (Hbmass) by CO-rebreathing. To analyze blood samples for a certain period of time after blood collection, it is necessary to know the stability of the COHb% during storage. The aim of the study was to determine the stability of COHb% at different storage temperatures over a period of up to 3 months. Twenty-five milliliters of cubital venous blood was taken from five volunteers (three females and two males) before and after inhalation of 0.8/1.0 mL/kg carbon monoxide and stored at +20°C and +4°C for 6 days and at -70°C for 12 weeks. Within the first 6 days, the blood was analyzed daily, then weekly for 12 weeks. Additionally, Hbmass was determined in 13 endurance athletes immediately after blood collection and after storage for 3 days (eight cyclists) and 7 days (five swimmers) at +20°C or +4°C. COHb% before and after CO inhalation was 1.56 ± 0.48 and 5.86 ± 1.12%, respectively, and remained unchanged over 6 days, with no difference between storage at different temperatures. The standard deviation (STD) over time was between 0.07% and 0.12%. Similarly, storage at -70°C for 12 weeks did not change COHb%, whereas STD was 0.07%. Hbmass determined immediately and, after 3 or 7 days of storage, differed by 10 ± 7 g and 15 ± 11 g corresponding to a typical error of 0.8% and 1.1%. Blood storage at +20°C and +4°C for 6 days and at -70°C for 12 weeks does not affect COHb% and has, therefore, no influence on Hbmass assessment.

Relationship between Blood Volume, Blood Lactate Quantity, and Lactate Concentrations during Exercise.

We wanted to determine the influence of total blood volume (BV) and blood lactate quantity on lactate concentrations during incremental exercise. Twenty-six healthy, nonsmoking, heterogeneously trained females (27.5 ± 5.9 ys) performed an incremental cardiopulmonary exercise test on a cycle ergometer during which maximum oxygen uptake (V·O2max), lactate concentrations ([La-]) and hemoglobin concentrations ([Hb]) were determined. Hemoglobin mass and blood volume (BV) were determined using an optimised carbon monoxide-rebreathing method. V·O2max and maximum power (Pmax) ranged between 32 and 62 mL·min-1·kg-1 and 2.3 and 5.5 W·kg-1, respectively. BV ranged between 81 and 121 mL·kg-1 of lean body mass and decreased by 280 ± 115 mL (5.7%, p = 0.001) until Pmax. At Pmax, the [La-] was significantly correlated to the systemic lactate quantity (La-, r = 0.84, p < 0.0001) but also significantly negatively correlated to the BV (r = -0.44, p < 0.05). We calculated that the exercise-induced BV shifts significantly reduced the lactate transport capacity by 10.8% (p < 0.0001). Our results demonstrate that both the total BV and La- have a major influence on the resulting [La-] during dynamic exercise. Moreover, the blood La- transport capacity might be significantly reduced by the shift in plasma volume. We conclude, that the total BV might be another relevant factor in the interpretation of [La-] during a cardio-pulmonary exercise test.

Cardiopulmonary exercise testing before and after intravenous iron in preoperative patients: a prospective clinical study.

BACKGROUND: Anemia is associated with impaired physical performance and adverse perioperative outcomes. Iron-deficiency anemia is increasingly treated with intravenous iron before elective surgery. We explored the relationship between exercise capacity, anemia, and total hemoglobin mass (tHb-mass) and the response to intravenous iron in anemic patients prior to surgery. METHODS: A prospective clinical study was undertaken in patients having routine cardiopulmonary exercise testing (CPET) with a hemoglobin concentration ([Hb]) < 130 g.l-1 and iron deficiency/depletion. Patients underwent CPET and tHb-mass measurements before and a minimum of 14 days after receiving intravenous (i.v.) Ferric derisomaltose (Monofer®) at the baseline visit. Comparative analysis of hematological and CPET variables was performed pre and post-iron treatment. RESULTS: Twenty-six subjects were recruited, of whom 6 withdrew prior to study completion. The remaining 20 (9 [45%] male; mean ± SD age 68 ± 10 years) were assessed 25 ± 7 days between baseline and the final visit. Following i.v. iron, increases were seen in [Hb] (mean ± SD) from 109 ± 14 to 116 ± 12 g l-1 (mean rise 6.4% or 7.3 g l-1, p = < 0.0001, 95% CI 4.5-10.1); tHb-mass from 497 ± 134 to 546 ± 139 g (mean rise 9.3% or 49 g, p = < 0.0001, 95% CI 29.4-69.2). Oxygen consumption at anerobic threshold ([Formula: see text] O2 AT) did not change (9.1 ± 1.7 to 9.8 ± 2.5 ml kg-1 min-1, p = 0.09, 95% CI - 0.13 - 1.3). Peak oxygen consumption ([Formula: see text] O2 peak) increased from 15.2 ± 4.1 to 16 ± 4.4 ml.kg.-1 min-1, p = 0.02, 95% CI 0.2-1.8) and peak work rate increased from 93 [67-112] watts to 96 [68-122] watts (p = 0.02, 95% CI 1.3-10.8). CONCLUSION: Preoperative administration of intravenous iron to iron-deficient/deplete anemic patients is associated with increases in [Hb], tHb-mass, peak oxygen consumption, and peak work rate. Further appropriately powered prospective studies are required to ascertain whether improvements in tHb-mass and performance in turn lead to reductions in perioperative morbidity. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT 033 46213.

Possible strategies to reduce altitude-related excessive polycythemia.

We sought to determine the effects of three treatments on hemoglobin (Hb) levels in patients with chronic mountain sickness (CMS): 1) descent to lower altitude, 2) nocturnal O2 supply, 3) administration of acetazolamide. Nineteen patients with CMS living at an altitude of 3,940 ± 130 m participated in the study, which consisted of a 3-wk intervention phase and a 4-wk postintervention phase. Six patients spent 3 wk at an altitude of 1,050 m (low altitude group, LAG), six received supplemental oxygen for 12 h overnight (oxygen group, OXG), and seven received 250 mg of acetazolamide daily (acetazolamide group, ACZG). Hemoglobin mass (Hbmass) was determined using an adapted carbon monoxide (CO) rebreathing method before, weekly during, and 4 wk postintervention. Hbmass decreased by 245 ± 116 g (P < 0.01) in the LAG and by 100 ± 38 g in OXG, and 99 ± 64 g in ACZG (P < 0.05, each), respectively. In LAG, hemoglobin concentration ([Hb]) decreased by 2.1 ± 0.8 g/dL and hematocrit by 7.4 ± 2.9% (both P < 0.01), whereas OXG and ACZG only trended toward lower values. Erythropoietin concentration ([EPO]) decreased between 81 ± 12% and 73 ± 21% in LAG at low altitude (P < 0.01) and increased by 161 ± 118% 5 days after return (P < 0.01). In OXG and ACZG, the [EPO] decrease was ∼75% and ∼50%, respectively, during the intervention (P < 0.01). Descent to low altitude (from 3,940 m to 1,050 m) is a fast-acting measure for the treatment of excessive erythrocytosis in patients with CMS, reducing Hbmass by 16% within 3 wk. Nighttime oxygen supplementation and daily acetazolamide administration are also effective, but reduce Hbmass by only 6%.NEW & NOTEWORTHY To our knowledge, this is the first study examining the effect of three different treatments [descending to lower altitude (from 3,900 m to 1,050 m), nocturnal oxygen supply, and administration of acetazolamide] on changes in hemoglobin mass in patients experiencing chronic mountain sickness (CMS). We report that descent to low altitude is a fast-acting measure for the treatment of excessive erythrocytosis in patients with CMS, reducing Hbmass by 16% within 3 wk. Nighttime oxygen supplementation and daily acetazolamide administration are also effective, but reduce Hbmass by only 6%. In all three treatments, the underlying mechanism is a reduction in plasma erythropoietin concentration due to higher oxygen availability.

Hemoglobin Mass and Blood Volume in Patients With Altitude-Related Polycythemia.

Patients with chronic mountain sickness (CMS) have a high hemoglobin concentration [Hb] due to increased hemoglobin mass (Hbmass) and possibly reduced plasma volume (PV). The values of Hbmass, PV and blood volume (BV) have been described differently, and the relationships between [Hb] and Hbmass or PV are poorly understood. This study obtained representative Hbmass, PV and BV data from healthy, high-altitude residents and CMS patients and quantified the dependency of [Hb] on Hbmass and PV. METHODS: Eighty-seven subjects born at high altitude (∼3,900 m) were enrolled. Thirty-four had CMS (CMS), 11 had polycythemia without CMS (intermediate, IM), 20 were healthy highlanders (HH), and 22 living near sea level (SL, 420 m) served as the sea level (SL) control group. Hbmass, PV and BV were determined using a CO-rebreathing method modified for assessing polycythemia patients. Furthermore, [Hb], hematocrit (Hct), plasma erythropoietin concentration [EPO] and blood gas and acid-base status were determined. RESULTS: In the HH group, Hbmass was 27% higher (940 ± 105 g) than in the SL group (740 ± 112 g) and 72% (1,617 ± 265 g) lower than in the CMS group. The PV in the HH group was similar to that in the SL group (-6%) and 15% higher than that in the CMS group (p < 0.001). In the HH group, the BV (5,936 ± 673 ml) did not differ from that in the SL group and was 28% lower than in the CMS group (7,606 ± 1075 ml, p < 0.001). Log [EPO] was slightly increased in the CMS group relative to the HH group (p < 0.01). All values in the IM group were between those in the HH and CMS groups. Hbmass and BV were positively correlated, and PV was negatively correlated with peripheral O2 saturation. Increased Hbmass and decreased PV contributed approximately 65 and 35%, respectively, to the difference in [Hb] between the HH (17.1 ± 0.8 g/dl) and CMS (22.1 ± 1.0 g/dl) groups. CONCLUSIONS: In CMS patients, the decrease in PV only partially compensated for the substantial increase in Hbmass, but it did not prevent an increase in BV; the decrease in PV contributed to an excessively high [Hb].

Acute Effects of Esports on the Cardiovascular System and Energy Expenditure in Amateur Esports Players.

Introduction: Esports is practiced by millions of people worldwide every day. On a professional level, esports has been proven to have a high stress potential and is sometimes considered equivalent to traditional sporting activities. While traditional sports have health-promoting effects through muscle activity and increased energy expenditure, amateur esports could represent a purely sedentary activity, which would carry potentially harmful effects when practiced regularly. Therefore, this study aims to investigate the acute effects of esports on the cardiovascular system and energy expenditure in amateur esports players to show whether esports can be considered as physical strain or mental stress or whether amateur esports has to be seen as purely sedentary behavior. Methods: Thirty male subjects participated in a 30-min gaming session, playing the soccer simulation game FIFA 20 or the tactical, first-person multiplayer shooter Counter-Strike: Global Offensive. Respiratory and cardiovascular parameters, as well as energy expenditure, blood glucose, lactate, and cortisol, were determined pre-, during, and post-gaming. Results: There were no significant changes in oxygen uptake, carbon dioxide output, energy expenditure, stroke volume, or lactate levels. Heart rate, blood glucose and cortisol decreased through the intervention until reaching their minimum levels 10 min post-gaming (Cortisolpre: 3.1 ± 2.9 ng/ml, Cortisolpost: 2.2 ± 2.3 ng/ml, p < 0.01; HRmin0.5: 82 ± 11 bpm, HRpost: 74 ± 13 bpm, p < 0.01). Conclusion: A 30-min esports intervention does not positively affect energy expenditure or metabolism in amateur esports players. Therefore, it cannot provide the same health-promoting effects as traditional sports participation, but could in the long-term rather cause the same potentially health-damaging effects as purely sedentary behavior. However, it does not trigger a negative stress response in the players. Deliberate physical activity and exercise routines adapted to these demands should therefore be part of the daily life of amateur esports players.

Cardiac stroke volume in females and its correlation to blood volume and cardiac dimensions.

We aimed to continuously determine the stroke volume (SV) and blood volume (BV) during incremental exercise to evaluate the individual SV course and to correlate both variables across different exercise intensities. Twenty-six females with heterogeneous endurance capacities performed an incremental cycle ergometer test to continuously determine the oxygen uptake (V̇O2), cardiac output (Q̇) and changes in BV. Q̇ was determined by impedance cardiography and resting cardiac dimensions by 2D echocardiography. Hemoglobin mass and BV were determined using a carbon monoxide-rebreathing method. V̇O2max ranged from 32 to 62 mL·kg-1·min-1. Q̇max and SVmax ranged from 16.4 to 31.6 L·min-1 and 90-170 mL, respectively. The SV significantly increased from rest to 40% and from 40% to 80% V̇O2max. Changes in SV from rest to 40% V̇O2max were negatively (r = -0.40, p = 0.05), between 40% and 80% positively correlated with BV (r = 0.45, p < 0.05). At each exercise intensity, the SV was significantly correlated with the BV and the cardiac dimensions, i.e., left ventricular muscle mass (LVMM) and end-diastolic diameter (LVEDD). The BV decreased by 280 ± 115 mL (5.7%, p = 0.001) until maximum exercise. We found no correlation between the changes in BV and the changes in SV between each exercise intensity. The hemoglobin concentration [Hb] increased by 0.8 ± 0.3 g·dL-1, the capillary oxygen saturation (ScO2) decreased by 4.0% (p < 0.001). As a result, the calculated arterial oxygen content significantly increased (18.5 ± 1.0 vs. 18.9 ± 1.0 mL·dL-1, p = 0.001). A 1 L higher BV at V̇O2max was associated with a higher SVmax of 16.2 mL (r = 0.63, p < 0.001) and Q̇max of 2.5 L·min-1 (r = 0.56, p < 0.01). In conclusion, the SV strongly correlates with the cardiac dimensions, which might be the result of adaptations to an increased volume load. The positive effect of a high BV on SV is particularly noticeable at high and severe intensity exercise. The theoretically expected reduction in V̇O2max due to lower SV as a consequence of reduced BV is apparently compensated by the increased arterial oxygen content due to a higher [Hb].

Effect of Exercise-Induced Reductions in Blood Volume on Cardiac Output and Oxygen Transport Capacity.

We wanted to demonstrate the relationship between blood volume, cardiac size, cardiac output and maximum oxygen uptake ( V . O2max) and to quantify blood volume shifts during exercise and their impact on oxygen transport. Twenty-four healthy, non-smoking, heterogeneously trained male participants (27 ± 4.6 years) performed incremental cycle ergometer tests to determine V . O2max and changes in blood volume and cardiac output. Cardiac output was determined by an inert gas rebreathing procedure. Heart dimensions were determined by 3D echocardiography. Blood volume and hemoglobin mass were determined by using the optimized CO-rebreathing method. The V . O2max ranged between 47.5 and 74.1 mL⋅kg-1⋅min-1. Heart volume ranged between 7.7 and 17.9 mL⋅kg-1 and maximum cardiac output ranged between 252 and 434 mL⋅kg-1⋅min-1. The mean blood volume decreased by 8% (567 ± 187 mL, p = 0.001) until maximum exercise, leading to an increase in [Hb] by 1.3 ± 0.4 g⋅dL-1 while peripheral oxygen saturation decreased by 6.1 ± 2.4%. There were close correlations between resting blood volume and heart volume (r = 0.73, p = 0.002), maximum blood volume and maximum cardiac output (r = 0.68, p = 0.001), and maximum cardiac output and V . O2max (r = 0.76, p < 0.001). An increase in maximum blood volume by 1,000 mL was associated with an increase in maximum stroke volume by 25 mL and in maximum cardiac output by 3.5 L⋅min-1. In conclusion, blood volume markedly decreased until maximal exhaustion, potentially affecting the stroke volume response during exercise. Simultaneously, hemoconcentrations maintained the arterial oxygen content and compensated for the potential loss in maximum cardiac output. Therefore, a large blood volume at rest is an important factor for achieving a high cardiac output during exercise and blood volume shifts compensate for the decrease in peripheral oxygen saturation, thereby maintaining a high arteriovenous oxygen difference.

Chronic Exposure to Low-Dose Carbon Monoxide Alters Hemoglobin Mass and V˙O2max.

By blocking the oxygen binding sites on the hemoglobin molecule, chronic low-dose carbon monoxide (CO) administration may produce similar effects to those of exposure to altitude. PURPOSE: This study aimed to determine the effect of chronic low-dose CO application on hemoglobin mass (Hbmass) and V˙O2max. METHODS: For 3 wk, 11 healthy and moderately trained male subjects inhaled a CO bolus five times per day to increase their HbCO concentration by ~5%. Another 11 subjects received a placebo. Hbmass, serum erythropoietin concentration, ferritin, and basic hematological parameters were determined before and weekly during and until 3 wk after the CO inhalation period. V˙O2max tests on a cycle ergometer were performed before and after the CO administration period. RESULTS: In the CO group, Hbmass increased from 919 ± 69 to 962 ± 78 g in week 3 (P < 0.001) and was maintained for the following 3 wk. Reticulocytes (%) and immature reticulocyte fraction significantly increased after 1 wk. Serum erythropoietin concentration tended to increase after 1 wk (P = 0.07) and was suppressed in the postperiod (P < 0.01). Ferritin decreased during the inhalation period (from 106 ± 37 to 72 ± 37 ng·mL, P < 0.001). V˙O2max tended to increase from 4230 ± 280 to 4350 ± 350 mL·min (P < 0.1) immediately after the inhalation period and showed a significant relationship to the change in Hbmass (y = 4.1x - 73.4, r = 0.70, P < 0.001). CONCLUSIONS: Chronic continuous exposure to low-dose CO enhances erythropoietic processes resulting in a 4.8% increase in Hbmass. The individual changes in Hbmass were correlated to the corresponding changes in V˙O2max. Examination of ethical and safety concerns is warranted before the implementation of low-dose CO inhalation in the clinical/athletic setting as a tool for modifying Hbmass.

Erythropoietic effects of low-dose cobalt application.

Cobaltous ions (Co2+ ) stabilize HIFα, increase endogenous erythropoietin (EPO) production, and may, therefore, be used as a performance-enhancing substance. To date, the dosage necessary to stimulate erythropoiesis is unknown. The aim of this study was, therefore, to determine the minimum dosage necessary to increase erythropoietic processes. In a first double-blind placebo-controlled study (n = 5), single oral Co2+ dosages of 5 mg (n = 6) and 10 mg (n = 7) were administered to healthy young men. Cubital venous blood and urine samples were collected before and up to 24 hours after Co2+ administration. In a second study, the same daily Co2+ dosages were administered for five days (placebo: n = 5, 5 mg: n = 9, 10 mg: n = 7). Blood and urine samples were taken the day before administration and at day 3 and day 5. Plasma [EPO] was elevated by 20.5 ± 16.9% at 5 hours after the single 5-mg administration (p < 0.05) and by 52.8 ± 23.5% up to 7 hours following the 10-mg Co2+ administration (p < 0.001). Urine [Co2+ ] transiently increased, with maximum values 3-5 hours after Co2+ ingestion (5 mg: from 0.8 ± 1.1 to 153.6 ± 109.4 ng/mL, 10 mg: from 1.3 ± 1.7 to 338.0 ± 231,5 ng/mL). During the five days of Co2+ application, 5 mg showed a strong tendency to increase [EPO], while the 10-mg application significantly increased [EPO] at day 5 by 27.2 ± 26.4% (p < 0.05) and the immature reticulocyte fraction by 49.9 ± 21.7% (p < 0.01). [Ferritin] was decreased by 12.4 ± 10.4 ng/mL (p < 0.05). An oral Co2+ dosage of 10 mg/day exerts clear erythropoietic effects, and 5 mg/day tended to increase plasma EPO concentration.

Effects of 3 Weeks of Oral Low-Dose Cobalt on Hemoglobin Mass and Aerobic Performance.

Introduction: Cobalt ions (Co2+) stabilize HIFα and increase endogenous erythropoietin (EPO) production creating the possibility that Co2+ supplements (CoSupp) may be used as performance enhancing substances. The aim of this study was to determine the effects of a small oral dosage of CoSupp on hemoglobin mass (Hbmass) and performance with the objective of providing the basis for establishing upper threshold limits of urine [Co2+] to detect CoSupp misuse in sport. Methods: Twenty-four male subjects participated in a double-blind placebo-controlled study. Sixteen received an oral dose of 5 mg of ionized Co2+ per day for 3 weeks, and eight served as controls. Blood and urine samples were taken before the study, during the study and up to 3 weeks after CoSupp. Hbmass was determined by the CO-rebreathing method at regular time intervals, and VO2max was determined before and after the CoSupp administration period. Results: In the Co2+ group, Hbmass increased by 2.0 ± 2.1% (p < 0.001) while all the other analyzed hematological parameters did not show significant interactions of time and treatment. Hemoglobin concentration ([Hb]) and hematocrit (Hct) tended to increase (p = 0.16, p = 0.1) and also [EPO] showed a similar trend (baseline: 9.5 ± 3.0, after 2 weeks: 12.4 ± 5.2 mU/ml). While mean VO2max did not change, there was a trend for a positive relationship between changes in Hbmass and changes in VO2max immediately after CoSupp (r = 0.40, p = 0.11). Urine [Co2+] increased from 0.4 ± 0.3 to 471.4 ± 384.1 ng/ml (p < 0.01) and remained significantly elevated until 2 weeks after cessation. Conclusion: An oral Co2+ dosage of 5 mg/day for 3 weeks effectively increases Hbmass with a tendency to increase hemoglobin concentration ([Hb]) and hematocrit (Hct). Because urine Co2+ concentration remains increased for 2 weeks after cessation, upper limit threshold values for monitoring CoSupp can be established.

Influence of Endurance Training During Childhood on Total Hemoglobin Mass.

Elite endurance athletes are characterized by markedly increased hemoglobin mass (Hbmass). It has been hypothesized that this adaptation may occur as a response to training at a very young age. Therefore, the aim of this study was to monitor changes in Hbmass in children aged 8-14 years following systematic endurance training. In the first study, Hbmass, VO2max, and lean body mass (LBM) were measured in 17 endurance-trained children (13 boys and 4 girls; aged 9.7 ± 1.3 years; training history 1.5±1.8 years; training volume 3.5 ± 1.6 h) twice a year for up to 3.5 years. The same parameters were measured once in a control group of 18 age-matched untrained children. Hbmass and blood volume (BV) were measured using the optimized CO-rebreathing technique, VO2max by an incremental test on a treadmill, and LBM by skin-fold measurements. In the second pilot study, the same parameters were measured in 9 young soccer athletes (aged 7.8 ± 0.2 years), and results were assessed in relation to soccer performance 2.5 years later. The increase in mean Hbmass during the period of study was 50% which was closely related to changes in LBM (r = 0.959). A significant impact of endurance training on Hbmass was observed in athletes exercising more than 4 h/week [+25.4 g compared to the group with low training volume (<2 h/week)]. The greatest effects were related to LBM (11.4 g·kg-1 LBM) and overlapped with the effects of age. A strong relationship was present between absolute Hbmass and VO2max (r = 0.939), showing that an increase of 1 g hemoglobin increases VO2max by 3.6 ml·min-1. Study 2 showed a positive correlation between Hbmass and soccer performance 2.5 years later at age 10.3 ± 0.3 years (r = 0.627, p = 0.035). In conclusion, children with a weekly training volume of more than 4 h show a 7% higher Hbmass than untrained children. Although this training effect is significant and independent of changes in LBM, the major factor driving the increase in Hbmass is still LBM.

Long-term intermittent hypoxia increases O2-transport capacity but not VO2max.

Long-term intermittent hypoxia, characterized by several days or weeks at altitude with periodic stays at sea level, is a frequently occurring pattern of life in mountainous countries demanding a good state of physical performance. The aim of the study was to determine the effects of a typical South American type of long-term intermittent hypoxia on VO2max at altitude and at sea level. We therefore compared an intermittently exposed group of soldiers (IH) who regularly (6 months) performed hypoxic-normoxic cycles of 11 days at 3550 m and 3 days at sea level with a group of soldiers from sea level (SL, control group) at 0 m and in acute hypoxia at 3550 m. VO2max was determined in both groups 1 day after arrival at altitude and at sea level. At altitude, the decrease in VO2max was less pronounced in IH (10.6 +/- 4.2%) than in SL (14.1 +/- 4.7%). However, no significant differences in VO2max were found between the groups either at sea level or at altitude, although arterial oxygen content (Ca(O(2) )) at maximum exercise was elevated (p < 0.001) in IH compared to SL by 11.7% at sea level and by 8.9% at altitude. This higher Ca(O(2) ) mainly resulted from augmented hemoglobin mass (IH: 836 +/- 103 g, SL: 751 +/- 72 g, p < 0.05) and at altitude also from increased arterial O(2)-saturation. In conclusion, acclimatization to long-term intermittent hypoxia substantially increases Ca(O(2) ), but has no beneficial effects on physical performance either at altitude or at sea level.

Effects of exercise training and a hypocaloric diet on female monozygotic twins in free-living conditions.

This paper aims to examine the similarities in effects of exercise training and a hypocaloric diet within overweight female monozygotic twin pairs and to assess differences in twin partners' responses depending on the timing of exercise bouts and main meals. Six previously untrained twin pairs (aged 20-37 years, body fat 35.8±6.3%) performed an identical exercise program (12 bouts endurance and 8 bouts resistance training) and took part in a nutrition counseling program for a period of 28 days. They pursued one identical goal: to lose body weight and fat. Each twin partner was randomly assigned to one of the two intervention groups: "exercise after dinner" (A) and "exercise before dinner" (B). Subjects followed a hypocaloric diet, supervised by a nutritionist, in free-living conditions. Reductions in body weight, waist and hip circumference, glucose tolerance, mean daily %fat intake, changes in morning resting energy rate and resting metabolic rate showed great variation between twin pairs, but only small variation within twin pairs. Thus, the genetic influence on the changes in most of the examined anthropometric and physiological variables was high. There was no influence of the specific timing on the dependent variables.