| Summary: | The overall aim of this thesis was to determine the effects of administration of recombinant human erythropoietin) r-HuEpo on endurance performance and to explore the psychosocial effects of taking this drug. In addition, the effects of injecting a Placebo, believed to be an erythropoietin-like substance was assessed, quantitatively and qualitatively, to determine what role the placebo effect may play in mediating the effects of r-HuEpo on endurance performance. All tests were also carried out in the field to ensure that studies had high ecological validity. The first study, presented in this thesis (Chapter 3), aimed to assess the validity of the Cosmed K4b2 portable metabolic analyser (K4b2) in measuring VO2 during submaximal and maximal running velocities in an outdoor environment. Nineteen trained male volunteers (age: 22.9 ± 1.0 years; weight: 74.1 ± 1.8 kg; height: 179.2 ± 1.4 cm; mean ±SD; VO2max 59.37 ± 0.30; mean ± SEM) completed maximal continuous incremental running tests which involved 3 minute exercise stages at running speeds between 8 to 16 km·h-1 in 2 km·h-1 increments. Measured gas exchange variables included fractional content of expired oxygen (FEO2) and fractional content of expired carbon dioxide (FECO2), oxygen uptake (VO2), carbon dioxide output (VCO2), ventilation (VE) and respiratory exchange ratio (RER). The Douglas bag method was used for comparison purposes. The typical error in VO2 measurement for the K4b2 outdoors compared to the Douglas bag method was 6.5 ml.kg-1.min-1. This degree of error for the measurement of was considered unacceptable and it was therefore decided that the K4b2 was not accurate enough to justify its use in subsequent studies. The aim of Chapter 4 was to assess the effect of r-HuEpo administration on haematological, psychological and performance measures. Seven well-trained males (age: 25.7 ± 2.2 y; BMI 22.5 ± 0.7 kg.m-2; VO2max: 57.7 ± 2.9 ml.kg-1.min-1) participated in a 10 week protocol divided into three phases; baseline (2 weeks), r-HuEpo administration (4 weeks) and post administration (4 weeks). Fifty IU.kg-1 subcutaneous injections were administered every two days during the r-HuEpo administration phase. Blood measures included the determination of hemoglobin concentration ([Hb]), haematocrit (Hct), reticulocytes (ret) and total haemoglobin mass (tHb). Cognitive State Anxiety Inventory CSAI-2) and Profile of Mood States (POMS) were utilised for psychological measures. Maximal oxygen uptake was measured and 3 km time trial performance was assessed at baseline, immediately post (i.e. at 4 weeks) and 4 weeks post r-HuEpo administration. Cognitive State Anxiety questionnaires were obtained immediately prior VO2max and 3 km time trials. Profile of Moods States questionnaires were obtained at baseline, immediately and 4 weeks post. At immediately the post r-HuEpo administration time-point, [Hb], Hct, ret and tHb significantly increased compared to baseline (P < 0.05) by 21.2%, 21.3%, 75.0% and 11.7%, respectively. At 4 weeks post r-HuEpo administration, [Hb], Hct and tHb decreased compared to the immediately post time-point, but remained significantly elevated compared to baseline by 7.9%, 9.3% and 6.9%, respectively (P < 0.05). Ret decreased to below baseline levels (by 41.7%) 4 weeks post r-HuEpo administration (P <0.05). VO2max did not significantly change (P = 0.07) over the course of the protocol, but was numerically 5.2% higher immediately post r-HuEpo administration when compared to baseline. Running speed at which the LT occurred was significantly higher by 6.4% (P < 0.05) immediately post r-HuEpo administration when compared to baseline. Running speed at OBLA was significantly higher immediately post r-HuEpo administration when compared to baseline by 5.9% (P < 0.05) and this remained elevated 4 weeks post, by 5.3%, when compared to baseline (P < 0.05). The %VO2max at LT was significantly higher immediately post r-HuEpo administration when compared to baseline by 6.6% (P < 0.05). Lactate turn-point values were also significantly higher (P < 0.05) immediately post r- HuEpo administration when compared to baseline and 4 weeks post by 9.6 and 7.6%,respectively. The CSAI-2 cognitive subscale decreased significantly (18.3%; P<0.05)immediately post. The POMS tension subscale decreased significantly immediately and 4 weeks post baseline (61% and 50% respectively; P<0.05). Three km time trial performance significantly improved immediately post r-HuEpo administration by 4.9% (P < 0.05) when compared to baseline. Faster times were sustained 4 weeks post r-HuEpo administration, when compared to baseline, by 3.9% (P < 0.05). Changes in [Hb]significantly correlated with changes in VO2max (r = 0.985; P = 0.016) with a tendency for changes in Hct to correlate with changes in VO2max (r = 0.807; P = 0.053). A significant negative relationship was found between changes in %VO2max at LT with changes in [Hb](r = -0.882; P = 0.048) and Hct (r = -0.926; P = 0.024) immediately post r-HuEpo administration. This study confirmed r-HuEpo increases [Hb] and Hct, and these were associated with improvements in VO2max. Three km time trial performance improved immediately post r-HuEpo administration by 4.9%. However, no clear association was found between [Hb], Hct or VO2max and 3 km performance, suggesting that factors other than changes in [Hb], Hct and VO2max are likely to have influenced running performance. Positive changes were also observed in psychological components which warrant further investigation. Performance benefits persisted 4 weeks post r-HuEpo administration. Chapter 5 aimed to assess the effect of r-HuEpo use on psychosocial factors associated with the practice. The use of substance abuse in sport, with the aim of improving performance, has been prevalent in sport for decades. Recent studies, have attempted to measure athlete viewpoints on doping in sport. However, few studies have been able report viewpoints related to illegal substance use, whilst participants are actually being administered with a banned substance. Six well-trained males (age: 26 ± 2 y; BMI: 22 ± 1 kg.m-2; VO2max: 58 ± 3 ml.kg-1.min-1) individually participated in semi-structured interviews after completing the trial involving the administration of r-HuEpo by subcutaneous injection for 4 weeks. Participants individually participated in semistructured interviews which were carried out within 2 weeks of completing the study. Varied responses were given in relation to psychosocial impacts and experiences. Five participants reported feeling a substantial performance enhancing effect. One individual expected a greater performance effect. Four individuals stood by their initial stance of ‘drugs should be banned in sport’. One individual entertained the idea that drugs should be allowed, but in a ‘controlled’ manner. One participant suggested that his views had changed, since being involved in the trial, sighting being geographically disadvantaged in the UK in comparison competitors with access to higher altitude. However, the emotions of guilt, shame and/or embarrassment were prominent themes which may be considered as a significant deterrent to doping. Chapter 6 aimed to determine whether an injectable placebo, claiming to be a legalsubstance with similar effects to r-HuEpo, would improve endurance running performance in simulated race conditions. Fifteen endurance-trained male volunteers (age: 27.5 ± 6.8 years, height: 1.79 ± 0.05 m, body mass: 73.4 ± 7.6 kg: BMI 22.9 ± 2.0 kg.m-2) successfully completed the randomised cross-over study design consisting of 3 km competition races before and after a 7-day ‘control’ phase and ‘placebo’ phase. During the placebo phase, participants self-administered daily subcutaneous saline injections in the belief that they were receiving a performance enhancing drug called OxyRBX.
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