Altitude will impact football performance through two separate and parallel pathways related to the hypobaric (physical) and hypoxic (physiological) components of terrestrial altitude: (a) the decrease in partial pressure of oxygen reduces maximal oxygen uptake and impairs "aerobic" performance by reducing maximal aerobic power, increasing the relative intensity of any given absolute level of work, and delaying recovery of high-energy phosphates between high-intensity "interval" type efforts; (b) the decrease in air density reduces air resistance which will facilitate high-velocity running, but will also alter drag and lift thereby impairing sensorimotor skills. These effects appear to have their greatest impact very early in the altitude exposure, and their physiological/neurosensory consequences are ameliorated by acclimatization, though the extent of restoration of sea level type performance depends on the absolute magnitude of the competing and living altitudes.

For decades altitude training has been used by endurance athletes and coaches to enhance sea‐level performance. Whether altitude training does, in fact, enhance sea level performance and, if so, by what means has been the subject of a number of investigations. Data produced principally by Levine and Stray‐Gundersen have shown that living for 4 weeks at 2500 m, while performing the more intense training sessions near sea level will provide an average improvement in sea level endurance performance (duration of competition: 7–20 min) of approximately 1.5%, ranging from no improvement to 6% improvement. This benefit lasts for at least 3 weeks on return to sea level. Two mechanisms have been shown to be associated with improvement in performance. One is an increase in red cell mass (∼8%) that results in an improved maximal oxygen uptake (∼5%). That must be combined with maintenance of training velocities and oxygen flux to realize the improvement in subsequent sea level performance. We find no evidence of changes in running economy or markers of anaerobic energy utilization. Our results have been obtained in runners ranging from collegiate to elite. Wehrlin et al. have recently confirmed these results in elite orienteers. While there are no specific studies addressing the use of living high, training low in football players, it is likely that an improvement in maximal oxygen uptake, all other factors equal, would enhance football performance. This benefit must be weighed against the time away (4 weeks) from home and competition necessary to gain these benefits.

For more than 60 years, muscle mechanical efficiency has been thought to remain unchanged with acclimatization to high altitude. However, recent work has suggested that muscle mechanical efficiency may in fact be improved upon return from prolonged exposure to high altitude. The purpose of the present work is to resolve this apparent conflict in the literature. In a collaboration between four research centers, we have included data from independent high-altitude studies performed at varying altitudes and including a total of 153 subjects ranging from sea-level (SL) residents to high-altitude natives, and from sedentary to world-class athletes. In study A (n=109), living for 20-22 h/day at 2500 m combined with training between 1250 and 2800 m caused no differences in running economy at fixed speeds despite low typical error measurements. In study B, SL residents (n=8) sojourning for 8 weeks at 4100 m and residents native to this altitude (n=7) performed cycle ergometer exercise in ambient air and in acute normoxia. Muscle oxygen uptake and mechanical efficiency were unchanged between SL and acclimatization and between the two groups. In study C (n=20), during 21 days of exposure to 4300 m altitude, no changes in systemic or leg VO2 were found during cycle ergometer exercise. However, at the substantially higher altitude of 5260 m decreases in submaximal VO2 were found in nine subjects with acute hypoxic exposure, as well as after 9 weeks of acclimatization. As VO2 was already reduced in acute hypoxia this suggests, at least in this condition, that the reduction is not related to anatomical or physiological adaptations to high altitude but to oxygen lack because of severe hypoxia altering substrate utilization. In conclusion, results from several, independent investigations indicate that exercise economy remains unchanged after acclimatization to high altitude.

Acute exposure to high altitude elicits respiratory alkalosis, and this is partially corrected by renal compensation. To determine the time course and magnitude of renal compensation during short-term moderate altitude exposure, we measured urine gas tensions and acid-base status in 48 healthy men and women at four levels of simulated altitude exposures. Each subject was exposed in pseudorandom order to simulated altitudes of 1780, 2085, 2455, and 2800 m in a decompression chamber for 24 h, separated by 1 week at sea level. Fresh urine was collected anaerobically at sea level and after 6 and 24 h of each altitude exposure. Urine pH increased significantly (p < 0.01) after 6 h at all altitudes and returned to baseline values by 24 h at the lowest altitudes. In contrast, urine pH remained elevated at the highest altitudes. The mean value of urine HCO at sea level was 1.67 +/- 0.25 mmol/L, increased significantly after 6 h at all altitudes, and then returned to near baseline after 24 h at three lower altitudes (1780, 2085, and 2455 m). However, it remained elevated at 2800 m. PCO2 in urine was significantly increased after 6 h and returned to baseline after 24 h at all altitudes. These results suggest that (1) short-term low to moderate altitude exposure results in a marked HCO diuresis, which may be caused by inhibition of the secretion of renal tubular H+, and (2) renal HCO compensation was completed by 24 h at low to moderate altitude, but still incomplete at higher altitude.

To engage in this debate we will address the following questions: what is the change in performance after adaptation to living high and training low (LHTL); what physiological mechanisms could be responsible; what is the evidence that a change in red cell volume (RCV) is one such mechanism; and what

This study attempted to contribute to standardization of blood testing in sport, and to investigate the effect of artificial dilution with saline. In 10 healthy, physically active males and 3 healthy physically active females hemoglobin (Hb), hematocrit (Ht), and % reticulocytes (%retics) were measured at different time points to look for possible fluctuations during day time, while the subjects had regular coffee breaks and lunch. In 7 of the subjects in a separate experiment 500 ml of saline were infused around 8 am and Hb, Ht, and %retics were measured before and every hour thereafter until 7 hours after infusion. In addition Ht was measured on a hematological analyzer as well as with a centrifuge. In a separate experiment the effect of tourniquet duration on Hb and Ht was studied in 9 of the subjects. The results show that Hb, Ht, and %retics are stable from 8 am to 4 pm, but that infusion of 500 ml of saline induces an acute decrease in Hb and Ht within one hour (Hb decreased from 15.2+/-0.9 g/dl to 14.5+/-1.0 g/dl, and Ht from 45.6+/-2.8 % to 44.0+/-2.5 %). The decline in Hb and Ht was maintained during the 7-hour observation period. Ht values of the same samples measured with a hematological analyzer and a centrifuge were not different. Application of the tourniquet did significantly affect Hb and Ht values only from two minutes, and thereafter Hb and Ht remained stable during the rest of the 5-minute tourniquet. With blood testing in sport these results have to be taken into consideration.

2319 PURPOSE: This study investigated the effect of exposure to short-term, intermittent hypobaric hypoxia (IHH) combined with sea-level training on running and swimming performance in well trained athletes. METHODS: 23 well-trained swimmers (13) and runners (10) were matched for gender, performance level and training history, and assigned to either hypobaric hypoxia (HYPO; simulated altitude of 4000–5500 m) or normoxia (NORM; 0–500 m) in a randomized, double blind, placebo controlled trial. Both groups rested in a hypobaric chamber for 3 h/day, 5 days a week, for 4 weeks. All subjects performed duplicate baseline time trials (3,000 m run, or 100 and 400 m swim), and maximal oxygen uptake tests on a treadmill and the swimming flume within three weeks before, and during the first and third week after the intervention. VO2 was measured by the Douglas bag method, with gas fractions being analyzed by mass spectrometry and ventilatory volumes using a Tissot spirometer. The best result of the baseline measurements was used for post test comparison using a 2-way RM ANOVA with main effects of test (Pre, Post 1, Post 2) and treatment (HYPO, NORM). RESULTS: No significant changes in time trial performance were observed for either the runners or swimmers, within or between groups. There was a main effect of test for VO2max (p = 0.02) and VEmax (p = 0.03). Post-hoc comparisons revealed an increase from Pre to Post 2 in VO2max (HYPO: +3.3%, p = 0.04; NORM: +0.9%, p = 0.10) and VEmax (p = 0.03; HYPO: +8.1%, p = <0.01; NORM: +1.2%, p = 0.64). No significant differences between groups were detected (group × test interaction, p = 0.3 and 0.1).TableCONCLUSION: This protocol of exposure to intermittent hypobaric hypoxia (3 h/day, 5 days/wk, during 4 wks) did not improve swimming or running performance in this group of well-trained athletes. We could not detect a significant difference in the change of VO2max or VEmax between groups under the carefully controlled conditions of these experiments. Supported by USOC, AIS, and ACSM (2003 International Scholar & Visiting Scholar Awards).

2309 Intermittent hypoxia (IH) is frequently used to improve performance in healthy athletes. However, IH is also used as a model for sleep apnea causing sustained sympathoexcitation and hypertension in laboratory animals, thus raising concern over the safety of this model. The PURPOSE of the study was to determine whether IH causes such detrimental hemodynamic effects in healthy trained athletes. METHODS: Twenty-two young elite athletes, 11 swimmers (5 m, 6 f), and 11 runners (6 m, 5 f) were randomized and assigned to either hypobaric hypoxia (HYPO: simulated altitude of 4000–5500m) or normoxia (NORM: 0–5000m) in a double blind, placebo controlled design. Both groups rested in a hypobaric chamber 3h/d, 5d/wk for 4 wks. Hemodynamic measurements including blood pressure (BP, automated cuff), heart rate (HR, ECG), cardiac output (Qc C2H2 rebreathing), total peripheral resistance (TPR = BP/Qc) and stroke volume (SV = Qc/HR) were conducted twice before and three days after the last chamber exposure in the sitting position. RESULTS: We observed no changes in any variable after this exposure (Table 1, values are MEAN ± SD). CONCLUSION: Intermittent hypobaric hypoxia did not alter BP or any aspect of hemodynamics in young endurance trained athletes.Table

2308 Conflicting studies of erythropoiesis have often used either carbon monoxide to estimate hemoglobin mass (HbmassCO) or Evans blue (EB) dye to estimate plasma volume (PVEB). Measuring hemoglobin concentration [Hb] and hematocrit (Hct) allows calculation of blood volume (BVCO = HbmassCO/[Hb] and BVEB = PVEB/(1-Hct)). PURPOSE: To measure HbmassCO and PVEB contiguously on athletes exposed to 4 wks of intermittent hypoxia (3h/day, 5d/wk at 4000–5500m) or double-blind placebo. METHODS: 48 pairs of BVCO and BVEB measurements were taken on 24 well-trained athletes (13 men, 11 women, 23 ± 8yrs, 174 ± 9cms, 68 ± 12kg; mean ± SD). HbmassCO was determined semi-supine from Δ%COHb after two doses of 99.9% CO; Dose1 = 20 or 15 ml, Dose2 = 1.5ml/kg or 1.25ml/kg for men and women, respectively. Samples were analysed (Radiometer OSM-3) in sextuplicate for %COHB and [Hb]. PVEB fully supine was determined without delay after CO-rebreathing. After an initial blood sample, ∼2.5 ml of EB was injected intravenously and blood re-sampled ∼10, 20 and 30 min later. The exact dye volume was determined as initial minus final syringe mass. After centrifugation, PVEB was calculated from time zero extrapolation of the regression derived from the 3 post-injection absorbances at 620 and 740 nm. The typical error (TE) of duplicate CO-rebreathing measures taken prior to treatment (= SD of difference scores/√2) was expressed as a percentage of the mean. RESULTS: BVCO = 5814 ± 1102 ml and BVEB = 6354 ± 1233 ml, respectively, and on average BVEB was 10 ± 8% higher. The linear regression between methods was BVEBD = 1.04 BVCO +320, r2 = 0.86, SEE = 465 ml. There was no change in BV in the hypoxic or placebo group for either method (F(1,21) = 0.27, p = 0.61). The TE for BVCO and HbmassCO before the intervention was 3.4% (95%CI = 2.7–4.8%) and 2.0% (95%CI = 1.6–2.7%), respectively. CONCLUSIONS: Our results do not support the assertion that CO may be distributed beyond the circulation to non-blood iron porphyrin molecules such as in muscle (myoglobin) and liver; CO did not overestimate BV. When carefully performed, both methods are suitable to measure blood volume and associated variables in athletes undergoing intermittent hypobaric hypoxia. Supported by USOC, AIS & ACSM* (2003 International & Visiting Scholar Award Programs).

2318 PURPOSE: To examine the effect of intermittent short-term hypobaric hypoxia combined with sea-level training on running and swimming economy. METHODS: 23 well-trained athletes (13 swimmers, 10 runners) were assigned to either hypobaric hypoxia (HYPO; simulated altitude of 4000–5500m) or normoxia (NORM; 0–500m) in a randomized, double blind design. Both groups rested in a hypobaric chamber 3 h/day, 5 days/wk for 4 weeks. Submaximal economy was measured twice BEFORE (within 3 weeks) and AFTER (1st and 3rd wk) the treatment period using sport specific protocols. Economy, defined as VO2 at a given velocity, was estimated from the relationship between VO2 and speed (Runners: 0% grade: 8, 10 & 12 mph for men; 8, 9 & 10 mph for women. Swimmers: 1.1, 1.2 & 1.3 m/s for men, and 1.0, 1.1 & 1.2 m/s for women). VO2 was measured during the last 60s of each stage using Douglas bags. Ventilation (Ve), heart rate (HR), and capillary lactate ([La-]) were measured during each stage. All measurements were conducted under normoxic conditions. Duplicate baseline measures were used to calculate Typical Error (TE = SD of differences/√2). The lowest VO2 for a given speed of the BEFORE values was used for post test comparison using a two-way, repeated measures ANOVA with main effects of time (pre, post1, and post2) and treatment (HYPO vs. NORM). RESULTS: TE was 5.0% {95% confidence limits 3.8 to 7.5}, 3.7% {2.9 to 5.5} & 4.9% {3.8 to 7.3} for speeds 1, 2 & 3 respectively. There was no change in economy (see table 1) within or between groups (ANOVA interaction p = 0.23, p = 0.29 & p = 0.65 for speeds 1, 2 & 3, respectively).Table 1: VO2 (L/min).There were no changes in HR or [La-]. Ve increased in both groups (HYPO: +11.7% and 10.6%, NORM +8.6% and 10.1% for Pre vs. Post 1 and Post 2 comparison, respectively). No differences between groups were found (p = 0.51, p = 0.76 & p = 0.85). CONCLUSION: Four weeks of intermittent hypobaric hypoxia did not improve submaximal economy in this group of well-trained swimmers and runners. Supported by USOC, AIS and ACSM* (2003 International Scholar Award & Visiting Scholar Award Programs).

This study was designed to test the hypothesis that intermittent normobaric hypoxia at rest is a sufficient stimulus to elicit changes in physiological measures associated with improved performance in highly trained distance runners. Fourteen national-class distance runners completed a 4-wk regimen (5:5-min hypoxia-to-normoxia ratio for 70 min, 5 times/wk) of intermittent normobaric hypoxia (Hyp) or placebo control (Norm) at rest. The experimental group was exposed to a graded decline in fraction of inspired O2: 0.12 (week 1), 0.11 (week 2), and 0.10 (weeks 3 and 4). The placebo control group was exposed to the same temporal regimen but breathed fraction of inspired O2 of 0.209 for the entire 4 wk. Subjects were matched for training history, gender, and baseline measures of maximal O2 uptake and 3,000-m time-trial performance in a randomized, balanced, double-blind design. These parameters, along with submaximal treadmill performance (economy, heart rate, lactate, and ventilation), were measured in duplicate before, as well as 1 and 3 wk after, the intervention. Hematologic indexes, including serum concentrations of erythropoietin and soluble transferrin receptor and reticulocyte parameters (flow cytometry), were measured twice before the intervention, on days 1, 5, 10, and 19 of the intervention, and 10 and 25 days after the intervention. There were no significant differences in maximal O2 uptake, 3,000-m time-trial performance, erythropoietin, soluble transferrin receptor, or reticulocyte parameters between groups at any time. Four weeks of a 5:5-min normobaric hypoxia exposure at rest for 70 min, 5 days/wk, is not a sufficient stimulus to elicit improved performance or change the normal level of erythropoiesis in highly trained runners.

2315 Intermittent hypoxia (IH) can induce ventilatory acclimatization in sedentary individuals, however, whether this adaptation occurs in athletes engaged in vigorous sea-level training has not been tested. PURPOSE: To examine measures of ventilatory acclimatization to IH in well-trained runners and swimmers. METHODS: 21 athletes (12 swimmers, 9 runners) were matched for gender, performance and training history, and randomly assigned to either hypobaric hypoxia (HYPO; simulated altitude of 4000–5500m) or normoxia (NORM; 0–500m) in a double-blind, placebo controlled design. Both groups rested 3 h.d−1, 5 d.wk−1 for 4 wk in a hypobaric chamber. Measures of resting ventilation (VE) and end-tidal PCO2 (PETCO2), isocapnic hypoxic ventilatory response (HVR; Δ VE/Δ SpO2), hypercapnic ventilatory response (HCVR; Δ VE/Δ PETCO2), and submaximal exercise VE were taken twice before IH or placebo (average = PRE), 3–4 d after (POST1), and 13–14 d after (POST2) the intervention. All measurements were conducted in normoxia. Results were analysed using a 2-way repeated measures ANOVA with two levels for group (HYPO, NORM) and three levels for day (PRE, POST1, POST2). RESULTS: The group × day interaction was nonsignificant for resting VE (p = 0.43), PETCO2 (p = 0.11), HVR (p = 0.84), HCVR (p = 0.92), and submaximal exercise VE (p = 0.93).TableCONCLUSIONS: Using the current protocol of IH, evidence of ventilatory acclimatization was not present in the HYPO group when compared to the NORM group. The brief daily periods of hypoxic exposure in this study may not have been a sufficient stimulus to induce ventilatory acclimatization in our subjects, who were engaged in high volume sea-level training.

2306 We examined the effect of 3 hours of intermittent hypobaric hypoxia on erythropoiesis. METHODS: 23 trained athletes were randomly assigned to either hypobaric hypoxia (HYPO; simulated altitude of 4000–5500m) or normoxia (NORM; 0–500m) in a double-blind, placebo controlled design. Both groups rested in a hypobaric chamber for 3 h/day, 5 day/wk, for 4 wks. Total Hb mass (CO rebreathing) was measured twice before and twice after treatment. Blood was drawn 8 times during the 10-wk study, (twice before, once per week during and twice after) and analyzed for [Hb], reticulocyte Hb, soluble transferin receptor (sTfr) and erythropoietin (EPO). Blood was also drawn twice (Wk 2, Wk 4) within 3hrs of chamber exposure and assayed for EPO.TableRESULTS: There were no differences between groups at baseline, nor were there any differences within or between groups for any variable except EPO. EPO did increase significantly in HYPO to acute chamber exposure (Wk2:11 ± 7 to 35 ± 14; Wk4:10 ± 5 to 29 ± 17), but not in NORM (Wk2:11 ± 5 to 15 ± 6; Wk4:13 ± 9 to 12 ± 6). CONCLUSIONS: These data indicate that there is an acute response to hypoxia demonstrated by a large increase in EPO levels post chamber exposure, but that there is no increase in erythroid mass to this mode of intermittent hypoxia as indicated by no change in total Hb mass, [Hb], reticulocyte Hb or sTfr. Further, the similarity of the acute response to hypoxia in Wks 2 and 4 indicate no hematologic acclimatization to the intermittent hypoxic exposure. Supported by USOC, AIS and ACSM*

BACKGROUND AND OBJECTIVES:We previously developed blood tests that were introduced at the Sydney 2000 Olympic Games to identify athletes injecting recombinant human erythropoietin (rHuEPO). The aim of this study was to re-analyse our existing database to develop models with heightened sensitivity, using wherever possible blood parameters measurable with appropriate standards of analytical performance. DESIGN AND METHODS:The principal database for this study was derived from a double-blind trial in which 57 recreational athletes were administered either rHuEPO or placebo. Standard discriminant analysis was used to derive two ON models (ON-hes and ON-he) and two OFF models (OFF-hr and OFF-hre) sensitive to accelerated and decelerated erythropoiesis respectively, utilising concentrations of hemoglobin (h), erythropoietin (e) and serum transferrin receptor (s), as well as percent reticulocytes (r). The ability of our models to detect rHuEPO administration was assessed by comparing model scores of subjects in the administration trial with the model scores of 1152 elite athletes from 12 countries. RESULTS:The ability of the new models to detect rHuEPO administration was generally higher than that of our previous models, particularly during phases when low doses of rHuEPO were used, and after injections had ceased. INTERPRETATION AND CONCLUSIONS. The increased stability of the new blood parameters facilitates transport of samples to central laboratories, and the heightened sensitivity of the new models makes them better than existing models for federations wishing to screen samples for urine testing and to identify and target suspect athletes for out-of-competition testing. However procedures should be incorporated that respect an elevated model score caused by genetic, health or environmental circumstances.

There is marked variability in the erythropoietin (Epo) and erythrocytic response to extreme high altitude among mountain dwellers, as well as to hypoxic training among athletes, at least in part because of the variation in the erythropoietic response to hypoxia. We hypothesized that this may be genetically determined. Forty-eight athletes were exposed to 24 h of simulated altitude to 2,800 m in a hypobaric chamber. Serum Epo concentrations were determined at baseline and after 24 h. The Epo responses ranged from -41 to 433% of baseline values after 24 h at simulated altitude. The association of the Epo response to hypoxia with the EPO gene and eight genes involved in Epo regulation utilizing 16 polymorphic dinucleotide repeats was examined. Initial analysis showed a possible association between the EPO gene (marker D7S477) and the increase of the Epo level (P = 0.018). We then tested the possibility that sequence abnormalities in the 3' and 5' hypoxia response elements (3' HRE) and (5' HRE) of the EPO gene could explain the differences in Epo response. We found a 3434 C --> T polymorphism in the 3' HRE sequence. However, this polymorphism showed no correlation with the differences in Epo levels. Further, when we analyzed two additional markers flanking the EPO gene by less than 0.3 cM, we found no association of the allelic variants at these loci with the Epo hypoxic response. In conclusion, we could find not convincing association between markers tightly linked to EPO or eight genes involved in Epo regulation and Epo differential responses to hypoxia.

Workload in running is related to body mass (BM), and therefore running economy is usually normalised for BM. During swimming however, adjusting for BM is not appropriate because workload is related to water resistance and not to BM since BM is being compensated for by buoyancy. Resistive forces during swimming are related to body length and body surface area. PURPOSE The purpose of this study was to examine the differences in swimming economy at submaximal speeds in subjects with a wide range in size, in absolute terms, normalised to body length (BL) and normalised to body surface area (BSA). METHODS Ten children (11.7 ± 0,8 yrs, BL 1.50 ±0.07m) and 13 adults (21.4 ± 3.7 yrs BL 1.85 ±0.06m) were tested during 4 submaximal workloads, each of 6 min duration. VO2 was measured with the Douglas bag method, using pacer lights at the bottom of the pool to control the velocity. BSA was estimated from BL and body mass measurements. In order to compare the two groups, the individual regression lines between VO2 and velocity cubed were averaged for the children and adults respectively. In order to compare VO2 adjusted for size, VO2 was divided by BL and BSA. RESULTS The absolute VO2 swimming at 1.0 m•s−1 for children and adults was 1.86 (±0.28) and 2.39 (±0.20) l•min−1 respectively (p < 0.01). Normalizing for BL the VO2 at 1.0 m•s−1 was 1.25 (±0.21) and 1.29 (±0.11) l•m−1•min−1, and BSA normalised VO2 at the speed of 1.0 m•s−1 was, 1.45 (±0.28) and 1.19 (±0.10) l•m−2•min−1 (p < 0.01) for the children and adults respectively. CONCLUSION The present study shows that there are no differences in swimming economy between children and adults when scaling for body length, that children have inferior swimming economy when scaling for BSA and that absolute oxygen uptake is lower for children than for adults for any given speed. We suggest that swimming economy should be normalised to body length when comparing individuals of varying size.

Introduction: Altitude training (“Living high” Training low') improves sea level performance in most endurance athletes. However, there is substantial individual variability in performance enhancement, due at least in part, to different erythropoietic (EPO) responses to altitude. Animal studies suggest that the EPO response to hypoxia may be transcriptionally regulated (Ou, et al, 1998), and thereby influenced by genetic mechanisms. Moreover, many highly polymorphic repeat sequences (dinucleotide, trinucleotide, or tetranucleotide) have been identified in the human genome within, or closely linked to genes specifically involved in hypoxia sensing and erythropoiesis. We hypothesized that the association of these polymorphisms with divergent phenotypic (increases in EPO) responses to high altitude would identify those genes that are responsible for individual variability in the erythropoietic response to hypoxia in humans. Methods: EPO concentration was measured in forty-eight competitive runners (32 men, 16 women) before and after 24-hours at a simulated altitude of 2800m. DNA obtained from leukocytes was amplified (PCR) and genotyped for polymorphic markers closely linked to candidate genes including, HIF-1α (transcriptional factor regulating EPO levels), pTEN (a down-regulator of the HIF-1α response), VHL (a posttranslational modulator of HIF-1α levels), RENOX (possible oxygen sensor in the kidney), EPO gene, and the EPO receptor. High EPO responders (top 17%) and low responders (bottom 23%) were examined for an association between any of these polymorphisms and the specific phenotype. Results: EPO responses ranged from ü41% to 400% of baseline values after 24 hours of simulated altitude. Two different polymorphic markers closely linked to the EPO gene were significantly associated with the phenotype on initial screening. When all athletes were considered, if one of the alleles of the marker was present (D7S477, homo or heterozygous) the increase in EPO was 135 ± 18% versus 78 ± 14% when it was absent (p = 0.02). Conclusion: These data support transcriptional regulation of EPO synthesis in humans. There may exist a specific haplotype of the EPO gene that can be used to predict the erythropoletic response to altitude and thereby response to altitude training. Molecular determinants of the EPO gene regulating these responses remain to be identified.

HISTORY: A 26-year-old, elite, sea level native, female, speed skater was participating in a 27-day Live High, Train Low altitude camp along with 6 other team members (2 women and 4 men). The athletes lived at 2500m and trained between 1400 and 3000m. The athlete complained of an unusual level of tiredness and dry throat from Day 5 to Day 14. Prior to the altitude camp at sea level, the athlete had a normal hemoglobin concentration and a high normal serum ferritin (153μgm/ml) and had not been placed on any iron supplementation. PHYSICAL EXAMINATION was unremarkable. DIFFERENTIAL DIAGNOSIS: R/O mild altitude sickness, dehydration, URTI, overwork, iron insufficiency TESTS AND RESULTS: As a routine monitoring screen for response to altitude and iron insufficiency venous blood was collected on K3EDTA on Day 2, Day 14 and Day 24 of the training camp. In this case the routine CBC was normal on all three occassions. The flow cytometry channel of the Advia 120 Hematology analyser provided the information listed in the Table below. The athlete's data are on the 3rd line of the Table and the Group means are on the 4th line of the Table. Note the marked decrease in CHr and the CHr/CHm ratio on Day 14 and the return to previous values on Day24. TREATMENT AND OUTCOME: The athlete was placed on 105mg of elemental iron in divided oral doses. Symptoms disappeared. Ten days later on repeat blood testing, reticulocyte hemoglobin content and CHr/CHm ratio had returned to previous values. Red Cell Hemoglobin Content exhibited a slight decrease reflecting the period of iron insufficient erythropoiesis. DIAGNOSIS: Iron insufficient erythropoiesis COMMENT: This case history illustrates the benefit of the new hematological flow cytometry analysers as a tool to monitor endurance athletes, particularily women athletes where iron deficiency is the most common nutritional deficit and particularily during altitude training where erythropoiesis may be accellerated. Iron insufficient erythropoiesis was identified and corrected in a timely fashion, at minimal cost and inconvenience to the athlete, prior to negative consequences to training and performance.