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 ([Formula: see text] O(2max)) 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 [Formula: see text] O(2max) 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 [Formula: see text] O(2max) 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 [Formula: see text] O(2max) (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

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

Introduction: Cobalt ions (Co2+) stabilize HIFa 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 5mg 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 signi fi cant 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 signi fi cantly 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

Erythropoietic effects of low-dose cobalt application

Cobaltous ions (Co2+) stabilize HIF alpha, 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

Disruption of tubulin-alpha4a polyglutamylation prevents aggregation of hyper-phosphorylated tau and microglia activation in mice

Pathologic oligomerization of hyper-phosphorylated Tau is a hallmark of tauopathies. Here the authors show that the loss of tubulin a4 polyglutamylation reverses tau hyperphosphorylation, oligomerization and microglia activation in a tauopathy mouse

The Microtubule Severing Protein Katanin Regulates Proliferation of Neuronal Progenitors in Embryonic and Adult Neurogenesis

Microtubule severing regulates cytoskeletal rearrangement underlying various cellular functions. Katanin, a heterodimer, consisting of catalytic (p60) and regulatory (p80) subunits severs dynamic microtubules to modulate several stages of cell division. The role of p60 katanin in the mammalian brain with respect to embryonic and adult neurogenesis is poorly understood. Here, we generated a Katna1 knockout mouse and found that consistent with a critical role of katanin in mitosis, constitutive homozygous Katna1 depletion is lethal. Katanin p60 haploinsufficiency induced an accumulation of neuronal progenitors in the subventricular zone during corticogenesis, and impaired their proliferation in the adult hippocampus dentate gyrus (DG) subgranular zone. This did not compromise DG plasticity or spatial and contextual learning and memory tasks employed in our study, consistent with the interpretation that adult neurogenesis may be associated with selective forms of hippocampal-dependent cognitive processes. Our data identify a critical role for the microtubule-severing protein katanin p60 in regulating neuronal progenitor proliferation in vivo during embryonic development and adult neurogenesis