Bo Belhage

Blood profiles in elite cross-country skiers: a 6-year follow-up

Following the doping scandals at the World Championships in cross‐country skiing in 2001, the International Ski Federation decided to generate individual blood profiles. From 2001 to 2007, 7081 blood samples from 1074 male and female elite cross‐country skiers were collected and analyzed for hemoglobin concentration [Hb] and % reticulocytes (%rets). Data were applied to blood algorithms wherefrom blood model scores were calculated. From 1997–1999 to 2001–2002, the mean [Hb] was reduced by 0.9u2003g/dL to 15.3u2003g/dL in male skiers and by 0.4u2003g/dL to 13.8 in female skiers. From 2002–2003 to 2006–2007, the combination of increases in [Hb] and decreases in %rets led to pronounced increases in mean OFF‐model scores. [Hb] was 0.2u2003g/dL higher at Olympic Games/World Championships (WOCs) than at World Cups competitions <4 weeks before and after WOCs. [Hb] and %rets increased with altitude in both genders. Since the introduction of an enlarged blood testing program, the mean [Hb] values were lowered to close to normal levels, but over the last 2–3 years there has been a small elevation and an increase in OFF‐model scores, which may indicate a change in the manipulations used to elevate the [Hb].

Erythropoietin Treatment Enhances Muscle Mitochondrial Capacity in Humans

Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8u2009weeks with oral iron (100u2009mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92u2009±u20095 to 113u2009±u20097u2009pmol·s−1·mg−1) and ETS (107u2009±u20094 to 143u2009±u200914u2009pmol·s−1·mg−1, pu2009<u20090.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

High-dose inhaled salbutamol has no acute effects on aerobic capacity or oxygen uptake kinetics in healthy trained men

The prevalence of asthma is higher among elite athletes than in the general population. This has resulted in the frequent use of anti‐asthmatic medication such as beta2‐agonists among asthmatic athletes. Beta2‐agonists are on the prohibited list of WADA. The use of the beta2‐agonist salbutamol is only permitted in therapeutic inhaled doses. Most studies have reported the lack of ergogenic effects of therapeutic doses of inhaled beta2‐agonists measured in maximal oxygen uptake. No previous studies have examined any possible effects of high‐dose inhaled salbutamol on oxygen uptake kinetics. We enrolled nine healthy well‐trained men in a randomized, blinded, placebo‐controlled crossover study. Subjects were randomized to inhalation of 40 puffs of 0.2u2003mg salbutamol or two placebo tablets and performed an incremental test to exhaustion and three submaximal tests at 75% of peak power to determine oxygen uptake kinetics. During the incremental test, there were no effects of inhaled salbutamol on VO2max in absolute or relative terms, and no effect on peak power and lactate threshold. During the submaximal test, we found no effects on the time constant, time delay, the mean response time or O2 deficit related to oxygen uptake kinetics. In conclusion, no ergogenic effect of a high dose of salbutamol on aerobic capacity was found.

Effect of Head Rotation on Cerebral Blood Velocity in the Prone Position

Background. The prone position is applied to facilitate surgery of the back and to improve oxygenation in the respirator-treated patient. In particular, with positive pressure ventilation the prone position reduces venous return to the heart and in turn cardiac output (CO) with consequences for cerebral blood flow. We tested in healthy subjects the hypothesis that rotating the head in the prone position reduces cerebral blood flow. Methods. Mean arterial blood pressure (MAP), stroke volume (SV), and CO were determined, together with the middle cerebral artery mean blood velocity (MCA Vmean) and jugular vein diameters bilaterally in 22 healthy subjects in the prone position with the head centered, respectively, rotated sideways, with and without positive pressure breathing (10u2009cmH2O). Results. The prone position reduced SV (by 5.4 ± 1.5%; P < 0.05) and CO (by 2.3 ± 1.9 %), and slightly increased MAP (from 78 ± 3 to 80 ± 2u2009mmHg) as well as bilateral jugular vein diameters, leaving MCA Vmean unchanged. Positive pressure breathing in the prone position increased MAP (by 3.6 ± 0.8u2009mmHg) but further reduced SV and CO (by 9.3 ± 1.3 % and 7.2 ± 2.4 % below baseline) while MCA Vmean was maintained. The head-rotated prone position with positive pressure breathing augmented MAP further (87 ± 2u2009mmHg) but not CO, narrowed both jugular vein diameters, and reduced MCA Vmean (by 8.6 ± 3.2 %). Conclusion. During positive pressure breathing the prone position with sideways rotated head reduces MCA Vmean ~10% in spite of an elevated MAP. Prone positioning with rotated head affects both CBF and cerebrovenous drainage indicating that optimal brain perfusion requires head centering.

Illusory Sensation of Movement Induced by Repetitive Transcranial Magnetic Stimulation

Human movement sense relies on both somatosensory feedback and on knowledge of the motor commands used to produce the movement. We have induced a movement illusion using repetitive transcranial magnetic stimulation over primary motor cortex and dorsal premotor cortex in the absence of limb movement and its associated somatosensory feedback. Afferent and efferent neural signalling was abolished in the arm with ischemic nerve block, and in the leg with spinal nerve block. Movement sensation was assessed following trains of high-frequency repetitive transcranial magnetic stimulation applied over primary motor cortex, dorsal premotor cortex, and a control area (posterior parietal cortex). Magnetic stimulation over primary motor cortex and dorsal premotor cortex produced a movement sensation that was significantly greater than stimulation over the control region. Movement sensation after dorsal premotor cortex stimulation was less affected by sensory and motor deprivation than was primary motor cortex stimulation. We propose that repetitive transcranial magnetic stimulation over dorsal premotor cortex produces a corollary discharge that is perceived as movement.

Voluntary respiratory control and cerebral blood flow velocity upon ice-water immersion.

INTRODUCTIONnIn non-habituated subjects, cold-shock response to cold-water immersion causes rapid reduction in cerebral blood flow velocity (approximately 50%) due to hyperventilation, increasing risk of syncope, aspiration, and drowning. Adaptation to the response is possible, but requires several cold immersions. This study examines whether thorough instruction enables non-habituated persons to attenuate the ventilatory component of cold-shock response.nnnMETHODSnThere were nine volunteers (four women) who were lowered into a 0 degrees C immersion tank for 60 s. Middle cerebral artery mean velocity (CBFV) was measured together with ventilatory parameters and heart rate before, during, and after immersion.nnnRESULTSnWithin seconds after immersion in ice-water, heart rate increased significantly from 95 +/- 8 to 126 +/- 7 bpm (mean +/- SEM). Immersion was associated with an elevation in respiratory rate (from 12 +/- 3 to 21 +/- 5 breaths, min(-1)) and tidal volume (1022 +/- 142 to 1992 +/- 253 ml). Though end-tidal carbon dioxide tension decreased from 4.9 +/- 0.13 to 3.9 +/- 0.21 kPa, CBFV was insignificantly reduced by 7 +/- 4% during immersion with a brief nadir of 21 +/- 4%.nnnDISCUSSIONnEven without prior cold-water experience, subjects were able to suppress reflex hyperventilation following ice-water immersion, maintaining the cerebral blood flow velocity at a level not associated with impaired consciousness. This study implies that those susceptible to accidental cold-water immersion could benefit from education in cold-shock response and the possibility of reducing the ventilatory response voluntarily.

Effects of an 8-weeks erythropoietin treatment on mitochondrial and whole body fat oxidation capacity during exercise in healthy males

Abstract The present investigation was performed to elucidate if the non-erythropoietic ergogenic effect of a recombinant erythropoietin treatment results in an impact on skeletal muscle mitochondrial and whole body fatty acid oxidation capacity during exercise, myoglobin concentration and angiogenesis. Recombinant erythropoietin was administered by subcutaneous injections (5000 IU) in six healthy male volunteers (aged 21 ± 2 years; fat mass 18.5 ± 2.3%) over 8 weeks. The participants performed two graded cycle ergometer exercise tests before and after the intervention where VO2max and maximal fat oxidation were measured. Biopsies of the vastus lateralis muscle were obtained before and after the intervention. Recombinant erythropoietin treatment increased mitochondrial O2 flux during ADP stimulated state 3 respiration in the presence of complex I and II substrates (malate, glutamate, pyruvate, succinate) with additional electron input from β-oxidation (octanoylcarnitine) (from 60 ± 13 to 87 ± 24 pmol · s−1 · mg−1 P < 0.01). β-hydroxy-acyl-CoA-dehydrogenase activity was higher after treatment (P < 0.05), whereas citrate synthase activity also tended to increase (P = 0.06). Total myoglobin increased by 16.5% (P < 0.05). Capillaries per muscle area tended to increase (P = 0.07), whereas capillaries per fibre as well as the total expression of vascular endothelial growth factor remained unchanged. Whole body maximal fat oxidation was not increased after treatment. Eight weeks of recombinant erythropoietin treatment increases mitochondrial fatty acid oxidation capacity and myoglobin concentration without any effect on whole body maximal fat oxidation.

Changes in red blood cell volume, plasma volume, and total blood volume after autologous blood collections

In certain clinical situations, persons may request to have multiple units of their own blood collected in advance of elective surgery (autologous blood donation) or to provide blood for transfusion for a friend or family member (directed blood donation). Only limited data are available for establishing safe guidelines and minimizing adverse acute physiologic effects when such blood collections are requested using an aggressive phlebotomy schedule. We would like to report the results of a study of the physiologic effects of multiple collections of whole blood comparing a conventional and an aggressive phlebotomy schedule. The results provide data that can be applied to establishing schedules for collecting multiple units of blood from healthy autologous or directed blood donors. We separated 16 healthy, male subjects (age, 26.7 6.3 years; height, 1.83 0.05 m; weight, 83 11 kg) into groups. For the 8 subjects in the aggressive collection group (ACG), we collected two bags of whole venous blood (approx. 900 mL) on Day 0 and one bag (approx. 450 mL) 7 days later. The whole blood was centrifuged and the 24 units of red blood cells (RBCs) were stored in saline-adenine-glucose-mannitol solution at 4°C and reinfused 26 3 days later. For the 8 subjects in the conventional collection group (CCG), we collected one bag (approx. 450 mL) of whole blood weekly for 3 weeks. For these 24 collections, we added 40 percent glycerol (wt/ vol) to the RBCs and stored them at 80°C for a mean of 72 5 days before reinfusion. After all blood collections, we infused an equal volume of 0.9 percent sodium chloride. We measured total blood volume (BV) by the modified CO-rebreathing technique. The mean of two precollection measurements made up the baseline values, and an additional 11 (ACG) and 12 (CCG) measurements were performed on each subject during the study period. Red blood cell volume (RBCV) and plasma volume (PV) were calculated from the BV using venous hemoglobin concentration and hematocrit levels, which were measured on a hematology analyzer (Advia 120, Bayer Diagnostics, Tarrytown, NY). Each day during a period of 4 weeks after the first phlebotomy, all subjects received a ferrous fumerate tablet containing 66 mg of ferrous iron. We performed a one-way repeated-measures analysis of variance to test for significance. Differences between measurement points were identified by the Holm-Sidak method. The significance level was set at p < 0.05. For subjects in the ACG, the RBCV decreased to a level significantly lower than baseline (p < 0.05) during the entire 26 3-day storage period (Fig. 1). Twenty-four hours after the first two bags were collected, the PV was unchanged, and the BV was 7.5 percent lower than baseline (Fig. 1). BV was significantly lower (p < 0.001) than baseline until 21 days after phlebotomy (Fig. 1). For subjects in the CCG, the RBCV decreased 18.1 percent with levels remaining significantly (p < 0.05) lower than baseline until 42 days after phlebotomy (Fig. 1). Their PV increased to levels significantly (p < 0.005) higher than baseline 14 and 21 days after the first phlebotomy, resulting in an unchanged BV during the entire study period (Fig. 1). The return of three bags of refrigerated autologous RBCs resulted in higher increases (16.1% in ACG) in RBCV compared to returning three bags of previously frozen RBCs (11.3% in CCG). Our data show a marked difference in the intravascular response to aggressive versus conventional schedules for collecting multiple units of whole blood from healthy subjects. It is well recognized that acute hypovolemia results in hemodynamic and hormonal responses, which act to reestablish normovolemia. Our results indicate that these compensatory mechanisms are insufficient when three 450-mL units (approx. 1.35 L) are collected within a short period of time (approx. 1 week) and that hypovolemia may persist for several weeks in the absence of blood replacement. On the other hand, in a less aggressive schedule, when one bag of whole blood is collected weekly, the body is able to reestablish the BV between phlebotomies. Furthermore, as evidenced in Fig. 1, more than 6 weeks—and probably 8 to 10 weeks—may be needed to fully reestablish the baseline RBCV. These data show that hypovolemia may persist for weeks after aggressive blood collections. The results can be extrapolated to clinical settings, for example, when there is a need to collect multiple units of autologous blood from LETTERS TO THE EDITOR