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.

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.