Hypoxic ventilatory response is correlated with increased submaximal exercise ventilation after live high, train low

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1 Eur J Appl Physiol (2005) 94: DOI /s ORIGINAL ARTICLE Nathan E. Townsend Æ Christopher J. Gore Allan G. Hahn Æ Robert J. Aughey Æ Sally A. Clark Tahnee A. Kinsman Æ Michael J. McKenna John A. Hawley Æ Chin-Moi Chow Hypoxic ventilatory response is correlated with increased submaximal exercise ventilation after live high, train low Accepted: 4 October 2004 / Published online: 18 December 2004 Ó Springer-Verlag 2004 Abstract This study tested the hypothesis that live high, train low (LHTL) would increase submaximal exercise ventilation ( _V E ) in normoxia, and the increase would be related to enhanced hypoxic ventilatory response (HVR). Thirty-three cyclists/triathletes were divided into three groups: 20 consecutive nights of hypoxia (LHTLc, n=12), 20 nights of intermittent hypoxia (4 5-night blocks of hypoxia interspersed by two nights of normoxia, LHTLi, n=10), or control (CON, n=11). LHTLc and LHTLi slept 8 10 h per night in normobaric hypoxia (2,650 m), and CON slept under ambient conditions (600 m). Resting, isocapnic HVR (D _V E / Dblood oxygen saturation) was measured in normoxia before (PRE) and after 15 nights (N15) hypoxia. Submaximal cycle ergometry was conducted PRE and after 4, 10, and 19 nights of hypoxia (N4, N10, and N19 respectively). Mean submaximal exercise _V E was increased (P<0.05) from PRE to N4 in LHTLc [74.4 (5.1) vs 80.0 (8.4) l min 1 ; mean (SD)] and in LHTLi [69.0 (7.5) vs 76.9 (7.3) l min 1 ] and remained elevated in both groups thereafter, with no changes observed in CON at any time. Prior to LHTL, submaximal _V E was N. E. Townsend Æ T. A. Kinsman Æ C.-M. Chow School of Exercise and Sport Science, Faculty of Health Sciences, University of Sydney, Lidcombe, Australia N. E. Townsend (&) Æ C. J. Gore Æ A. G. Hahn Æ T. A. Kinsman Department of Physiology, Australian Institute of Sport, ACT 2617 Canberra, Australia nathan.townsend@ausport.gov.au Tel.: Fax: S. A. Clark Æ J. A. Hawley Exercise Metabolism Group, School of Medical Science, RMIT University, Melbourne, Australia R. J. Aughey Æ M. J. McKenna Muscle, Ions and Exercise Group, School of Human Movement, Recreation and Performance, Centre for Aging, Rehabilitation and Exercise Science, Victoria University of Technology, Melbourne, Australia not correlated with HVR, but this relationship was significant at N4 (r=0.49, P=0.03) and N19 (r=0.77, P<0.0001). Additionally, the increases in submaximal _V E and HVR from PRE to N15 N19 were correlated (r=0.51, P=0.02) for the pooled data of LHTLc and LHTLi. These results suggest that enhanced hypoxic chemosensitivity contributes to increased exercise _V E in normoxia following LHTL. Keywords Simulated altitude Æ Endurance athlete Æ Peripheral chemosensitivity Introduction It is common practice for athletes to engage in altitude training with the aim of improving sea-level performance (Hahn et al. 2001). A fundamental adaptation to altitude exposure is ventilatory acclimatisation, whereby resting and exercise ventilation gradually increase over several days at altitude, thus leading to the development of chronic hypocapnia (Bisgard and Forster 1996). A primary mechanism responsible for ventilatory acclimatisation is an increase in the hypoxic ventilatory response (HVR), reported to occur following continuous altitude residence (Sato et al. 1992, 1994), short-term intermittent hypoxic exposure (Garcia et al. 2000), or live high, train low (LHTL) hypoxic exposure (Townsend et al. 2002). An increase in HVR facilitates the progressive rise in ventilation ( _V E ) despite an unchanged hypoxic stimulus and hypocapnic inhibition. Interestingly, upon return to normoxic conditions, hyperventilation continues and then diminishes in a timedependent manner to normal levels of _V E (Bisgard and Forster 1996). Several authors have reported increased exercise _V E in athletes after return from natural altitude (Buskirk et al. 1967; Faulkner et al. 1967; Daniels and Oldridge 1970; Dill and Adams 1971), and recently an increase in submaximal exercise _V E was also observed following LHTL (Gore et al. 2001).

2 208 The influence of resting HVR on exercise hyperpnoea at sea level is debatable. No relationship between resting HVR and the ventilatory equivalent for oxygen [ _V E /rate of oxygen uptake ( _V O 2 )] at maximal exercise was observed in two studies (Hopkins and McKenzie 1989; Gavin et al. 1998); however, others found a significant positive correlation at submaximal (Martin et al. 1978) and maximal exercise (Harms and Stager 1995). Since it has been suggested the peripheral chemoreceptors act as a fine tuning mechanism regulating exercise hyperpnoea (Whipp 1994), it seems plausible that increased peripheral chemoreceptor gain may contribute to enhanced exercise _V E. The hypothesis that enhanced peripheral chemosensitivity would be related to increased exercise hyperpnoea in normoxia following 7 days of intermittent hypoxia (1 hæday 1, 4,500 m) was tested recently (Katayama et al. 2002). The HVR increased after intermittent hypoxia, but no change in submaximal exercise _V E was found. The authors therefore concluded that changes in hypoxic chemosensitivity had little effect on exercise _V E (Katayama et al. 2002). In contrast, subjects exposed to hypoxia lasting 8 10 h per night (3,000 m) exhibited increased submaximal exercise _V E in normoxia after 11 days (Gore et al. 2001). Also, we reported a progressive decrease in endtidal partial-pressure of carbon dioxide (P ET CO 2 ), which reached a plateau after three nights LHTL (2,650 m) hypoxic exposure, indicating achievement of ventilatory acclimatisation (Townsend et al. 2002). These results are consistent with findings in goats, i.e. that continued hyperventilation upon removal of a hypoxic stimulus required chronic hypocapnia during acclimatisation (Engwall and Bisgard 1990). Only one study has investigated hyperventilation upon return to normoxia following the early stage of ventilatory acclimatisation in humans (Dempsey et al. 1979). In that study, when subjects were returned to sea level after 3 5 days acclimatisation at 4,300 m altitude, resting _V E remained elevated for up to 24 h. Therefore, it appears that only several days of hypoxic acclimatisation may be required to produce hyperventilation upon return to normoxia. However, whether LHTL for only 8 10 h per night increases exercise _V E in normoxia after only a few nights, and whether changes in HVR influence the response at this early stage, have not been examined. Since we have already established that LHTL increases HVR and induces ventilatory acclimatisation characterised by chronic hypocapnia (Townsend et al. 2002), the purpose of this study was to test the hypothesis that, during 20 days of LHTL, the following would occur: (1) exercise _V E in normoxia would increase within 3 5 days and remain increased thereafter, and (2) the increase in HVR would modulate this response. If _V E is elevated after acclimatisation, but no relationship exists with the enhanced HVR, this would imply that only a central mechanism, and not a short-term alteration in peripheral chemosensitivity influences the enhancement of _V E. Methods Subjects Thirty-three male, endurance-trained athletes (9 triathletes, 24 cyclists) gave written informed consent to participate in this study, which was approved by the Australian Institute of Sport Ethics Committee. Subjects were divided into three groups matched for initial maximal oxygen consumption ( _V O 2max ). These included a live high, train low consecutive group (LHTLc), a live high, train low intermittent group (LHTLi), and a control group (CON). Two subjects did not complete all testing procedures and were not included in the final data analysis. Therefore, final group numbers were LHTLc 11, LHTLi 9, and CON 11. Normal lung function (Gore et al. 1995) was verified in all subjects using a spirometer (Model AS600, Minato Medical Science, Osaka, Japan). Subject characteristics for each group are presented in Table 1. Subjects maintained their own training throughout the experimental protocol, and kept a daily log of duration, mode, and frequency of training. Experimental design The LHTLc spent 8 10 hæday 1 for 20 consecutive nights in a room enriched with nitrogen, at a simulated altitude of 2,650 m (inspired oxygen = 16.3%; ambient barometric pressure 710 mmhg). The LHTLi group also slept a total of 20 nights under the same hypoxic stimulus, however, after every fifth night in hypoxia, subjects slept two nights in normoxia at a natural altitude of 600 m (Canberra, Australia). Details of the altitude house operation have been described previously (Ashenden et al. 1999). The CON group slept under Canberra ambient conditions during the entire experimental protocol. Each subject completed two HVR tests 1 2 weeks prior to hypoxic exposure, and the average was used as the baseline measure (PRE). The HVR was measured Table 1 Physiological and anthropometric characteristics of the subject population. All data are presented as means (SD). LHTLc Live high, train low consecutive group, LHTLi live high, train low intermittent group, CON control group, _V O 2peak, peak oxygen consumption, FVC, forced vital capacity, FEV 1 forced expiratory volume (L s) CON (n=11) LHTLc (n=11) LHTLi (n=9) Height (cm) (5.4) (7.2) (12.2) Mass (kg) 71.3 (6.0) 75.2 (10.6) 70.9 (9.2) Age (years) 26.2 (4.5) 26.5 (5.5) 26.0 (4.1) _V O 2peak (LÆmin 1 ) 4.75 (0.22) 4.83 (0.53) 4.55 (0.48) _V O 2peak (mlækg 1 Æmin 1 ) 67.0 (4.3) 64.9 (7.5) 65.5 (4.4) FVC (L) 5.39 (0.55) 6.42 (1.05) 5.68 (1.40) FEV 1 (L) 4.54 (0.84) 5.04 (0.72) 4.57 (1.15)

3 209 again on the day after three (N3), ten (N10), and fifteen (N15) nights of hypoxia, and again 3 days after the final exposure (POST). Respiratory responses during submaximal cycle ergometry were measured prior to (PRE) and on the day after four (N4), ten (N10) and nineteen (N19) nights of hypoxic exposure. Additionally, respiratory responses during maximal cycling were measured at PRE and N19. It was not always possible to conduct HVR and exercise testing on the same days due to testing commitments as part of a larger study investigating lactate metabolism and muscle adaptations (Clark et al. 2004). Hypoxic ventilatory response The HVR was determined using a modification of the method of Weil et al. (1970) as previously described (Townsend et al. 2002). All tests were conducted in a fasted state, in normobaric normoxia, within 2 h of waking. No alcohol or caffeine was consumed during the preceding 12 h, and subjects rested in a chair for 10 min immediately prior to each test. During the HVR, subjects were given reading material and listened to quiet music to minimise behavioural influences on breathing. Upon commencement of the test, subjects breathed room air for 5 min through a two-way respiratory valve (Model R2700, Hans Rudolph, Kansas City, Mo.) while wearing a nose-clip. _V E was measured using a LÆmin 1 heated pneumotachometer (Model 3719, Hans Rudolph) coupled to a pneumotach system (Model RSS 100HR, Hans Rudolph). The pneumotachometer was calibrated prior to every test with a 1 L volumetric syringe. Expirate was sampled continuously from a mouth port and fractions of expired oxygen (F E O 2 ) and carbon dioxide (F E CO 2 ) were measured using an Ametek S-3A oxygen analyser and a CD-3A carbon dioxide analyser, respectively (Applied Electrochemistry, Pittsburgh, Pa.). Immediately prior to each test, gas analysers were calibrated with three precision-grade gases (BOC Gases, Sydney, Australia) spanning the range encountered during the HVR tests. Heart rate and blood oxygen saturation (SpO 2 ) were measured via finger-tip pulse oximetry (model 505-US, Criticare Systems, Waukesha, Wis.). Analogue output signals from the pneumotach system, the gas analysers, and the pulse oximeter, were sampled at 50 Hz and time-synchronised using custom dataacquisition software. After breathing room-air, 100% nitrogen was gradually added to the inspired gas mixture over a period of 6 9 min. The test was terminated when SpO 2 remained at or below 75% for three successive breaths. During the test, 100% carbon dioxide was bled into the inspired air to maintain isocapnia at the resting P ET CO 2 determined during room-air breathing immediately prior to each test. The manual addition of nitrogen and carbon dioxide to the inspired gas mixture was facilitated by real-time display of F E O 2 and F E CO 2 on a computer monitor coupled with the analogue outputs from the gas analysers. HVR data analysis To allow time for stable resting ventilatory patterns to be achieved, only the last 60 s of room-air breathing was used for calculation of HVR, resting _V E and P ET CO 2. Ventilatory data were initially sampled as individual breath-by-breath values, and the average SpO 2 during each breath was calculated. In cases of severe ventilatory abnormality (e.g. swallowing, coughing), the abnormal data points were deleted. All ventilatory data points were then smoothed using a rolling average with an interval of five breaths. Linear regression was conducted on the relationship between _V E and SpO 2 to determine the slope of the line, and this was taken as the measure of HVR [litres per minute per per cent (L min 1 Æ% 1 )]. Exercise testing All subjects performed submaximal and maximal cycle ergometry on a calibrated, electromagnetically braked cycle ergometer (Lode, Groningen, The Netherlands) in normoxia at the Australian Institute of Sport Physiology Laboratory (600 m natural altitude). The submaximal cycling test used an incremental protocol with stage durations of 6 min, with 1 min rest periods between stages for collection of venous blood samples. Venous blood was analysed for lactate concentration using a blood gas analyser (ABL 700, Radiometer Medical) as part of another study, results of which are reported elsewhere (Clark et al. 2004). The starting workload for the submaximal cycling test was 100 W, which increased by 50 W each stage until 200 W, thereafter increasing by 15 W each stage until a power output producing a blood lactate concentration of 4 mmolæl 1 was reached. Subjects were instructed to select a preferred cycling cadence during their initial test, and to cycle at this cadence for all trials thereafter. During PRE and after N19 only, the submaximal test was followed by a maximal incremental test after a 5 min rest. Subjects resumed cycling at the power output where a lactate concentration of 4 mmolæl 1 was attained, and the workload was increased by 25 W every 150 s until volitional exhaustion. During the last 4 min of each submaximal stage, and during the entire maximal test, subjects breathed through a two-way respiratory valve (model R2700, Hans Rudolph) with expired gas directed to a custombuilt, automated, indirect calorimetry system. Expired gas was collected in two 200 L aluminised foil bags (Scholle Industries, Elizabeth, South Australia) using 30 s sampling periods rotating between bags in continuous series. A 13 L precision-bore piston (Tufnol, Birmingham, UK) instrumented for real-time measurement of displacement, temperature, and pressure

4 210 was used to determine volume, and mixed expired gas was analysed for F E O 2 and F E CO 2 using gas analysers (Ametek model S3A and model CD-3A, respectively). Prior to all experimental trials, the gas analysers were calibrated with three precision-grade gases (accurate to ± 0.02%) spanning the physiological range. Values for _V O 2, carbon dioxide production ( _V CO 2 ), and _V E were calculated from every 30 s sample, and consecutive measures were added to obtain minute values. Ventilatory equivalents for oxygen ( _V E / _V O 2 ) and carbon dioxide ( _V E / _V CO 2 ) were calculated from the respective minute values. Since the workload at which 4 mmolæl 1 lactate concentration was achieved varied across subjects due to differences in body size and training status, the number of stages completed between subjects was variable (i.e. the number of workloads required to attain 4 mmolæl 1 varied between 6 and 12) and, therefore, the main effect of workload could not be computed. Also, since differences in intensity are known to influence the potentiating effect of exercise on the resting HVR (Weil et al. 1972), we reasoned that variability could be introduced into the results if only a single absolute workload was examined because this would represent unequal relative exercise intensity between subjects. Therefore, below the workload that corresponded to 4 mmolæl 1 lactate concentration, the values for respiratory variables were averaged across all workloads (which were identical for all tests on an individual) to obtain a single mean submaximal value for each subject. For each of the workloads below 4 mmolæl 1 lactate concentration, respiratory data were averaged for the last 2 min of each workload. For the maximal test, respiratory values were taken as those achieved at peak oxygen consumption ( _V O 2peak ), defined as the highest _V O 2 obtained over an entire minute period. Results Submaximal exercise There was a significant group day interaction for all submaximal exercise ventilatory measures (Fig. 1). Submaximal exercise _V E increased in both LHTLc and LHTLi from PRE to N4 and remained elevated thereafter, whereas, no significant change was observed for CON. Submaximal exercise _V E was significantly greater in LHTLc than LHTLi at both N10 and N15 (Fig. 1A). When the data for LHTLc and LHTLi were pooled, Statistical analysis All values are reported as means (SD). Exercise respiratory variables were analysed using a two-way, repeated-measures analysis of variance with three levels for group (CON, LHTLc, and LHTLi), and four levels for day for the submaximal test (PRE, N4, N10, and N19), or two levels for day for the maximal test (PRE and N19). Significant interactions were subsequently analysed using the Tukey HSD post-hoc procedure. Relationships between variables were examined using linear regression conducted on the pooled data of both LHTLc and LHTLi groups. Since post LHTL measures of HVR and submaximal and maximal exercise could not be completed on the same days, the HVR tests conducted at N15 were correlated with respiratory responses from exercise testing at N19, which represented the closest temporal match near completion of the LHTL intervention. Statistical significance was accepted at P < 0.05, and all analyses were completed using Statistica software version 5.0 (StatSoft, Tulsa, Okla.). Fig. 1 Ventilatory responses during submaximal cycle ergometry in well trained athletes before (PRE) and during [4 (N4), 10 (N10), and 19 (N19) nights of hypoxia] live high, train low (LHTL) hypoxic exposure. LHTL consecutive group (LHTLc), LHTL intermittent group (LHTLi), and control group (CON). _V E Ventilation, _V O 2 rate of oxygen uptake, _V CO 2 rate of carbon dioxide production, BTPS body temperature and pressure (saturated with water vapour). *LHTLc significantly different from PRE. **LHTLc significantly different from PRE and CON and LHTLi. LHTLi significantly different from PRE. Values are means (SD). P<0.05

5 211 submaximal exercise _V E values at N4, N10, and N19 were elevated by 8.9 (5.4)%, 10.3 (9.4)%, and 8.2 (4.0)% respectively, compared with their PRE value. Similarly, both _V E / _V O 2 (Fig. 1B) and _V E / _V CO 2 (Fig. 1C) increased from PRE to N4 in LHTLc and LHTLi, and remained elevated thereafter (P < 0.05), whereas, no change occurred in CON. The group day interaction was not significant for either mean submaximal _V O 2 (F = 0.57, P = 0.75) or _V CO 2 (F = 0.43, P = 0.86). Maximal exercise There were no significant changes from PRE to N19 in either maximal _V E (Fig. 2A) or _V E / _V O 2 (Fig. 2B) for any group. There was, however, a significant group - day interaction for _V E / _V CO 2 (Fig. 2C). Compared with PRE values, maximal exercise _V E / _V CO 2 was increased at N19 in LHTLc (P < 0.05) and tended to increase in LHTLi (P = 0.07). The increase in _V E / _V CO 2 at N19 was mainly due to decreased _V CO 2 (P < 0.05) during maximal exercise in LHTLc [5.11 (0.56) vs 5.03 (0.53) LÆmin 1 ] and in LHTLi [4.96 (0.51) vs 4.75 (0.58) LÆmin 1 ]. There was no significant difference in _V O 2peak (group day interaction; P=0.49) from PRE to N19 for LHTLc [4.83 (0.53) vs 4.86 (0.40) LÆmin 1 ], LHTLi [4.55 (0.48) vs 4.62 (0.54) LÆmin 1 ] and CON [4.75 (0.22) vs 4.92 (0.40) LÆmin 1 ]. Training volume Average training volume was higher in LHTLc [15.8 (3.7) hæweek 1 ] than CON [11.0 (3.0) hæweek 1 ; P < 0.05], but neither differed significantly from LHTLi [13.3 (3.7) hæweek 1 ]. Discussion The main finding of this study was that exposure to only four nights of 2,650 m simulated altitude increased submaximal exercise _V E measured in normoxia by 9%. Submaximal exercise _V E remained elevated during all further exercise testing throughout the intervention, and HVR and exercise ventilation The HVR significantly increased in both LHTLc and LHTLi groups, as detailed elsewhere (Townsend et al. 2002); hence, HVR and P ET CO 2 results are not reported here. At PRE, the correlations between HVR and submaximal _V E (r = 0.38, P = 0.10; Fig. 3A) or maximal _V E (r = 0.26, P = 0.28; Fig. 4A) were non-significant, as was the correlation between HVR and submaximal _V E / _V O 2 (r = 0.30, P = 0.20). If the 11 CON subjects were added to the pooled data at PRE, correlations between HVR and submaximal _V E (r = 0.27, P = 0.14), maximal _V E (r = 0.10, P = 0.58), and submaximal _V E / _V O 2 (r = 0.27, P = 0.20) remained non-significant. For the LHTLc and LHTLi pooled data only, there was a significant relationship between HVR at N3 and submaximal _V E at N4 (r = 0.49, P = 0.02). This relationship approached significance at N10 (r = 0.41, P = 0.07), and was significant between HVR at N15 and submaximal _V E at N19 (r = 0.77, P < ; Fig. 3B), as well as HVR at POST and submaximal _V E at N19 (r = 0.48, P = 0.03). HVR at N15 was correlated with maximal _V E (r = 0.59, P = 0.008; Fig. 4B), and submaximal _V E / _V O 2 (r = 0.44, P = 0.05) measured at N19. The correlation between the change in submaximal _V E from PRE to N19, and the change in HVR from PRE to N15 was significant for the pooled LHTL groups (r = 0.51, P = 0.02; Fig. 5A). This relationship was not significant in CON (Fig. 5B). Fig. 2 Ventilatory responses during maximal cycle ergometry in well trained athletes PRE and N19 of LHTL hypoxic exposure. Values are means (SD). P<0.05

6 212 Fig. 3A, B Relationship between resting, isocapnic hypoxic ventilatory response (HVR) and _V E measured during submaximal cycle ergometry. Linear regression line and 95% confidence intervals represent pooled data for llhtlc and LHTLi groups. A PRE measures, B HVR measured after N15, and exercise _V E measured after N19. All tests were conducted in normoxia, and all ventilatory volumes are in BTPS a strong correlation with HVR existed after days of LHTL. Additionally, the increase in HVR from PRE to N15 was significantly correlated with the increase in submaximal _V E from PRE to N19. These relationships were not evident in the CON group, indicating that it was a specific effect of LHTL rather than some influence of the experimental procedures or training in Canberra at 600 m natural altitude. This study is the first to report an increase in submaximal exercise _V E in normoxia after a period of only 4 days of LHTL in well-trained endurance athletes. Early studies of altitude-acclimatised subjects demonstrated that the hyperpnoea of exercise was greater in acclimatised humans during acute normoxia compared with sea-level baseline values (Dempsey et al. 1972; Forster and Klausen 1973), and increased maximal _V E has been observed in trained athletes returning to sea level after 2 4 weeks of altitude training (Buskirk et al. 1967; Faulkner et al. 1967; Daniels and Oldridge 1970; Dill and Adams 1971). Furthermore, one study has reported increased submaximal _V E after 11 and 23 nights of LHTL in triathletes (Gore et al. 2001). Collectively, Fig. 4A, B Relationship between resting, isocapnic HVR and _V E measured during maximal cycle ergometry. Linear regression line and 95% confidence intervals represent pooled data for LHTLc and LHTLi groups. A PRE measures, B HVR measured after N15, and exercise _V E measured after N19. All tests were conducted in normoxia and all ventilatory volumes are in BTPS these results support our finding of increased exercise _V E in normoxia after hypoxic acclimatisation. Previously, we reported that HVR was significantly enhanced after 3 days of LHTL exposure in the same group of subjects (Townsend et al. 2002), and since the peripheral chemoreceptors are thought to modulate ventilation during exercise (Whipp 1994), we hypothesised that following LHTL, a positive relationship between HVR and exercise _V E would exist. This hypothesis was supported by the finding that HVR was significantly correlated with submaximal _V E after a period of 3 4 days of LHTL altitude acclimatisation. Interestingly, this relationship was only moderate after 3 4 days and 10 days, however, it was a strong relationship after days of LHTL, at which point also, the HVR attained its peak value (Townsend et al. 2002). Furthermore, the increase in HVR from PRE to N15 was correlated with the increase in submaximal exercise _V E from PRE to N19. However, the HVR showed a progressive increase during LHTL, whereas submaximal exercise _V E did not continue to increase after N4 in a similar fashion as the HVR. These results suggest that while the HVR exerted some influence on exercise _V E after hypoxic acclimatisation, it was not the sole mechanism regulating this change. The relationship between hypoxic chemosensitivity and exercise _V E following 7 days of intermittent hypoxia (1 h day 1, 4,500 m) was recently examined (Katayama et al. 2002). The authors reported no increase in exercise _V E despite an increase in HVR. In a similar study, intermittent hypoxia (2,500 m) was administered 45 minæd 1, 5 dæweek 1 for 5 weeks during exercise (Levine et al. 1992). Despite an increase in the HVR, the authors observed no change in exercise _V E or _V E / _V O 2. The lack of increase in _V E, however, may be explained by the suggestion that ventilatory de-acclimatisation

7 213 Fig. 5A, B Relationship between the change in HVR (PRE to N15), and the change in submaximal exercise _V E (PRE to N19). A Pooled data for LHTLc and LHTLi, B CON group responses over the same period. All ventilatory volumes are in BTPS from hypoxia involves a mechanism related to central chemoreception (Bisgard and Forster 1996). It was demonstrated in goats that persistent hyperventilation upon removal from hypoxia required prolonged hypocapnia during acclimatisation to isolated carotid body hypoxia (Engwall and Bisgard 1990). Therefore, in the studies by Katayama et al. (2002) and Levine et al. (1992), the 1 h daily hypoxic exposures may have been an insufficient stimulus to elicit prolonged hypocapnia (Katayama et al. 2002), since the onset of ventilatory acclimatisation requires at least 2 3 h of sustained hypoxia (Garcia et al. 2001; Mahamed et al. 2003). When hypoxia was sustained for 8 10 h, we observed a reduction in P ET CO 2 after just one night when measured approximately 1 h upon return to normoxia (Townsend et al. 2002). In that study, P ET CO 2 was further reduced after two more nights of hypoxia, suggesting that chronic hypocapnia was progressively developed, which is typical during the early phase of ventilatory acclimatisation. Additionally, it has been reported that central chemosensitivity is enhanced following chronic hypoxia exposure lasting 48 h (Fatemian and Robbins 1998; Tansley et al. 1998), but not after 2 weeks of daily intermittent hypoxic exposures lasting 20 min (Mahamed and Duffin 2001). A limitation to our study, though, is that we did not conduct a measure of central chemosensitivity. Regardless, the finding that P ET CO 2 was decreased (Townsend et al. 2002) taken in conjunction with enhanced submaximal exercise _V E of the same subjects during the early phase of acclimatisation, is consistent with the theory that chronic hypocapnia is required during hypoxic acclimatisation to produce sustained hyperventilation after returning to normoxia (Dempsey and Forster 1982; Bisgard and Forster 1996). In contrast to studies reporting elevated maximal exercise _V E in athletes following continuous altitude training (Buskirk et al. 1967; Faulkner et al. 1967; Daniels and Oldridge 1970; Dill and Adams 1971), we did not find increased maximal _V E after LHTL in our subjects. The discrepancy between findings may be related to the protocol of hypoxic exposure. We used discontinuous hypoxic exposure of 8 10 hæday 1 administered overnight, whereas all the studies reporting increased maximal _V E upon return to sea level used continuous altitude for approximately days. Unfortunately, none of those studies included a control group matched for training volume and intensity, therefore, an effect of training independent of the altitude intervention cannot be ruled out. Our finding that submaximal, but not maximal exercise _V E, was increased following LHTL is consistent with the finding that highly trained athletes may be limited by mechanical constraints of the pulmonary system at high workloads (Dempsey 1986). Highly trained athletes may exhibit considerable expiratory flow limitation during maximal exercise (Dempsey et al. 1984; Johnson et al. 1992), and it has been suggested there is little adaptability in the pulmonary system even with several months of training (Dempsey 1986). Therefore, it seems unlikely that only 19 days of LHTL should increase maximal _V E in a group of well-trained cyclists and triathletes. Increased submaximal _V E due to simulated or natural altitude acclimatisation may have a bearing on athletic performance and/or physiological responses to normal training. Enhanced _V E during intense exercise at sea level is potentially detrimental to performance, since leg blood flow may be compromised in order to compensate for the greater oxygen cost of breathing (Wetter et al. 1999). Alternatively, chronically elevated _V E may lead to respiratory muscle training, which has been demonstrated to be beneficial for cycling endurance performance (McMahon et al. 2002). Inadequate exercise hyperpnoea may contribute to the development of exercise induced arterial hypoxaemia (EIAH) even at submaximal workloads (Rice et al. 1999; Durand et al. 2000). Whether or not EIAH limits performance, though, remains an unresolved question (Dempsey and Wagner 1999) and, thus, whether a hypoxia-induced elevation in exercise hyperpnoea in subjects exhibiting EIAH is beneficial to performance is yet to be elucidated. Furthermore, the finding that _V E was elevated after only 4 days raises the question of whether adaptations secondary to this response occur in athletes who may participate in LHTL programs lasting up to several weeks or even months. In conclusion, 8 10 h per night exposure to simulated altitude equivalent to 2,650 m induced a 9% increase in submaximal exercise _V E after only 4 days in

8 214 trained endurance athletes. Baseline resting isocapnic HVR was only weakly correlated with exercise _V E, however, after 3 4 days of LHTL, this relationship was moderate and was strong after days. Furthermore, the increase in exercise _V E between baseline and days of LHTL was correlated with the corresponding increase in HVR. These results suggest that enhanced hypoxic chemosensitivity modulates elevated exercise hyperpnoea during short-term reintroduction to normoxia after acclimatisation to LHTL. Acknowledgements The authors wish to acknowledge the support of BOC Gases Australia for supply of resources, equipment, and technical assistance, Mr. Colin Mackintosh for software development and support, and Mr. Rob Shugg and Mr. Evan Lawton for technical assistance. This study was funded by an Australian Research Council grant (no. C ). 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