Exercise stimulus increases ventilation from maximal to supramaximal intensity

Eur J Appl Physiol (1995) 70:115-125 © Springer-Verlag 1995 K.I. Norton . B. Squires • L.H. Norton • N.P. Craig P. McGrath • T.S. Olds Exercise stimulus increases ventilation from maximal to supramaximal intensity Accepted: 2 August 1994 Abstract This study investigated the influence of an exercise stimulus on pulmonary ventilation (12E)during severe levels of exercise in a group of ten athletes. The altered ventilation was assessed in relation to its effect on blood gas status, in particular to the incidence and severity of exercise induced hypoxaemia. Direct measurements of arterial blood were made at rest and during the last 15 s of two intense periods of cycling; once at an intensity found to elicit maximal oxygen uptake (l?Ozm~x; MAX) and once at an intensity established to require 115% of l;'Ozmax (SMAX). Oxygen uptake (1)'O2) and ventilatory markers were continually recorded during the exercise and respiratory flow-volume loops were measured at rest and during the final 30 s of each minute for both exercise intensities. When compared to MAX exercise, the subjects had higher ventilation and partial pressure of arterial oxygen (PaO2) during the SMAX intensity. Regression analysis for both conditions indicated the levels of PaOz and oxygen saturation of arterial blood (S~O2) were positively correlated with relative levels of ventilation during exercise. It was apparent that mechanical constraints to ventilate further were not present during the MAX test since the subjects were able to elevate l;z during SMAX and attenuate the level of hypoxaemia. This was also confirmed by analysis of the flow volume recordings. These data support the conclusions firstly, K.I. Norton ( I ~ ) " T.S. Olds Human Bioenergetics Laboratory, School of Sport and Leisure Studies, The University of New South Wales, P.O. Box 88, Oatley, NSW 2233, Australia B. Squires • P. McGrath Department of Physiology, University of Newcastle, New South Wales, Newcastle, Australia L.H. Norton John Hunter Hospital, Newcastle, New South Wales, Australia N. P.Craig The South Australian Sports Institute, Adelaide, South Australia that overwhelming mechanical constraints on l/E were not present during the MAX exercise, secondly, the subjects exhibiting the most severe hypoxaemia had no consistent relationship with any measure of expiratory flow limitation, and thirdly, ventilatory patterns during intense exercise are strong predictors of blood gas status. Key words Exercise-induced hypoxaemia Exercise stimulus - Flow-volume loops Supramaximal exercise • Ventilatory drives Introduction Traditionally, it has been accepted that the pulmonary system does not represent a limitation to maximal performance in humans (Cerretelli and di Prampero 1987). This assumption is based upon findings that arterial blood remains at or near resting oxygen saturation (S~O2) levels (i.e. %S~O2 equal to or greater than 95%) even during intense exercise, in the healthy but untrained population. Although exceptions to this generalisation had occasionally been reported (Holgram and Linderholm 1958; Rowell et al. 1964), it was not until the last decade that several detailed studies have confirmed the existence of exercise induced hypoxaemia (EIH) in athletes exercising maximally at sea level (Dempsey et al. 1984; Powers et al. 1989a; TorreBueno et al. 1985). It has now become evident from other studies that in a substantial number of high-performance athletes performing aerobic exercise at maximal intensity, the pulmonary system does represent a limitation to performance (Hopkins and McKenzie 1989; Powers et al. 1988, 1989b; Williams et al. 1986). The most obvious sign of this pulmonary insufficiency has been an exaggerated widening of the alveolar-arterial POz difference ( P A - a O ; ) with increasing exercise intensities (Johnson et al. 1992; Warren et al. 1991). It has also been 116 reported that arterial oxygen tension ( P a O 2 ) may decrease to below 8 kPa (60 mmHg) and that there is a concomitant drop in %S~O2 to as low as 85%-86% (Dempsey et al. 1984; Powers et al. 1989b; Williams et al. 1986). Although several mechanisms to explain these findings have been proposed, the precise etiology of EIH remains to be determined (Johnson et al. 1992; Powers and Williams 1987). It has been suggested that one potential cause of EIH may be a relative hypoventilation during maximal exercise (Dempsey et al. 1984; Miyachi and Tabata 1992). If there is a less than adequate hyperpnoeic response during intense exercise, this may result in a suboptimal alveolar oxygen partial pressure (PAO2) and a corresponding reduced driving force for 02 diffusion according to Fick's Law. There has been considerable debate, however, as to whether athletes with the lowest SaO2 levels during exercise do (Dempsey et al. 1984; Miyachi and Tabata 1992; Powers et al. 1984; 1988; Warren et al 1991), or do not (Powers et al. 1992; Williams et al. 1986) exhibit reduced levels of relative ventilation [indicated by a low ventilatory equivalent for oxygen (pulmonary ventilation/oxygen uptake, 12E/1202) I. Some authors have suggested a mechanical limitation exists in trained subjects exhibiting EIH, preventing further 1/E during intense exercise (Johnson et al. 1992). On the other hand, it has been shown that 12E can be increased during severe exercise in some, but not all, subjects following chemical stimulation using either dead space loading (McParland et al. 1991), increased inspired CO2 breathing (Johnson et al. 1992; Fig. 5) or pharmacological chemoreceptor stimulation (Naeije et al. 1993). This study was designed to determine the relationship between aspects of 12E during exercise at maximal and supramaximal levels, and the development of hypoxaemia in a group of high-performance athletes. Specifically, we addressed the question of whether absolute and relative levels of 12E are altered as a consequence of an exercise stimulus beyond that intensity found to elicit maximum oxygen uptake (!)O2m,x). We analysed the change in 1/E in relation to the development and severity of EIH. In addition, we investigated possible reasons for suboptimal ventilatory responses during exercise. Methods EIH (Powers et al. 1988; Williams et al. 1986). The subjects gave informed consent after being given a detailed description of the test protocol, special emphasis being placed upon the risks associated with invasive measurements. All procedures used were performed in accordance with the guiding ethics for human experimentation outlined by the National Health and Medical Research Council of Australia. Experimental protocol Prior to the test day, the subjects visited the laboratory on at least two occasions for familiarization with the equipment and personnel and so that measurements of 1202max and mechanical efficiency could be made. The test for 1202max involved a standard cycle ergometer protocol employing 2-min intervals, beginning at 150 W and increasing in 25-W increments until the subjects reached exhaustion. Mechanical efficiency while cycling was determined for each subject using five 4-rain stages at progressively increasing submaximaI exercise intensities as has been previously described (Olds et al. 1993). The mean 1202 during the last 2 rain of each stage was regressed against exercise intensity (in watts). Regression lines were then used to determine appropriate supramaximal exercise intensities as outlined below. On the day of the experiment, the subjects were measured for stretch standing height to the nearest 0.1 cm with a wall stadiometer and body mass to the nearest 50 g with a calibrated beam scale. Following this, the subjects assumed a supine position on a preparation table and electrodes were placed in the standard V5 position for electrocardiogram recording. A radial artery catheter was inserted and the subjects then moved to the ergometer and were instructed to sit comfortably in position on the cycle for at least 15 rain prior to exercise. The experimental protocol involved two exercise tests on the cycle ergometer, each of up to 4-rain duration. The tests were performed on the same day with 1 h separating each of the following intensities: (1) once at an intensity found to elicit 1202max (MAX), and (2) once at an intensity estimated to require 115% of 1202max (SMAX). Each of the intensities was conducted in an identical fashion and the order was randomized to preclude any bias arising from the exercise administration. Warm-up was not standardised, rather the subjects were instructed to prepare as they would for competition. Warm-up was then followed by a compulsory 3 min rest period. Baseline, pre-exercise blood samples were taken at the end of the rest period, prior to each exercise test. Three maximal voluntary flow-volume loops were then performed by the subjects. This was done while in position on the cycle and connected to the respiratory valve apparatus in the same way as that used during the exercise tests. The subjects remained attached to the respiratory apparatus following these manoeuvres to facilitate correct placement of the exercise tidal flow-volume loops within the voluntary loops. In addition to pre-exercise measurements, the following variables were measured during each test: continuous measurements of heart rate (HR) and respiratory variables, exercise tidal flow-volume loops over 30 s intervals beginning at 30, 90, 150, and 210 s, and an arterial blood sample during the last 15 s of exercise as the subject was nearing exhaustion. Subjects Gas analysis Ten healthy, non-smoking adult men participated in this study. The subjects were all well trained but varied in performance abilities. Included in the group were one amateur cyclist, four competitive triathletes, one mountain bike cyclist eight times national champion), and four Olympic track cycling medalists (including one world champion). Trained athletes were deliberately targeted for this study to improve the likelihood of observing significant levels of The g o 2 m e a s u r e m e n t s were determined using a breath-by-breath metabolic assessment system (Ametek, model OCM2). For further analysis, and to overcome some of the random variations in ventilatory measurements, data were averaged and plotted for 15-s intervals. The gas analysis system incorporated a lowresistance respiratory valve (Rudolph, model 2700) attached to an 117 inertially-compensated unidirectional turbine flowmeter on the inspiratory side. Expired gas samples passed through short, large diameter tubing (34 mm) to a 4-1 mixing chamber. Gas samples were continually monitored for 02 and CO2 concentrations by fast response analysers (Ametek S3A/IO2 and CD 3A CO2 analysers, respectively). A time delay factor was used to align inspiratory gas volumes with expiratory gas analysis. The gas analysers were calibrated prior to each test with gases whose concentrations had been verified densitometrically. The flow meter was calibrated throughout the range 0-4001.min- 1 constant flow and 0-1801.min- 1 puisatile flow rate using a Tissot spirometer and calibrated syringe, respectively. Resistance to gas flow was measured (as a pressure drop) for both the inspiratory and expiratory sides of the full system during these calibration checks using a manometer. Resistance to flow at 225 l'min -1 was less than 5 cmH20 for both sides of the system and within the range recommended (Thoden 1991). exercise by adhesive tape. Peak temperature was recorded within 2-rain post-exercise and used to adjust blood gas tensions. A second blood sample (15 ml) was collected during the exercise test immediately following the first (blood gas) sample. This was subsequently divided for analysis of lactate, catecholamine (adrenaline and noradrenaline) and potassium concentrations. Lactate concentration was determined spectrophotometrically (Sigma kit #726-UV) and serum potassium assessed using flame photometry (Instrumentation Laboratory, model 943). Plasma catecholamine concentrations were assessed via gas chromatography-mass spectrometry (Duncan et al. 1988). The sensitivity of the catecholamine assays was 0.05pmol- 1- i with a coefficient of variation of a known standard being less than 0.4%. All blood analyses were performed in duplicate and the mean value used in further procedures. Cycle ergometer Flow-volume analysis Flow-volume data were measured using a modified pneumotachograph (P.K. Morgan, model 098) incorporated into the respiratory valve. The pneumotachograph was attached between the mouthpiece and Rudolph respiratory valve so that a minimal increase in dead space (approximately 40 ml) resulted. The voltage signal resulting flom the measured pressure differences was sent to a computer for conversion to real-time flow-volume loops. These loops were recorded in discrete files, each containing approximately 30 s of measurements. Average flow-volume loops for each file were deduced by visual inspection when data were superimposed on one another in a computer printout. The estimated mean loops for each subject were then scanned into a computer program which allowed minor smoothing to be performed. Composite group mean flowvolume loops were based on the average of all individual loops (breaths) produced by analysis of the final 30 s of measurements for each subject in both exercise tests. The exercise loops were plotted relative to the group mean forced vital capacity, peak voluntary inspiratory and expiratory flow rates and expiratory reserve volumes (difference between exercise end tidal volume and end expiration in the voluntary ventilation test). These values were all determined from measurements taken on the mean flow-volume loops of the individual subject. All tests were conducted on a sport-specific, air-braked ergometer, details of which have been published previously (Craig and Walsh 1989). The ergometer was calibrated throughout the physiological range of exercise intensities using a dynamic calibration torque meter. During each test the power output in watts and total work done in kilojoules were continuously measured from flywheel revolution rates and stored on disk using a computer interface. The subjects were given instructions about the required power output for each test and were given instantaneous feedback of pedal cadence via a digital display. The test was concluded if the subject reached 4rain or failed to hold the pedal cadence within 3 rpm of the required cadence for more than 5 s. Statistical analyses Paired Wilcoxon tests were used to determine if there were any differences between group means in the exercise treatments and between selected pre-exercise and exercise conditions. Least squares linear regression analysis was employed to determine the relationship between dependent and independent variables. A probability level of 0.05 was accepted to indicate significance for all statistical analyses. Results Blood collection and analysis A catheter was inserted under local anaesthetic (procaine hydrochloride) into the radial artery of the nondominant arm and sutured into position by an experienced anaesthetist. Catheter patency was maintained using positive pressure infusion (3 ml'h -1) of heparinised saline (10 U. mi- 1). Withdrawal of blood was performed in an identical fashion prior to and during the exercise tests. Following the removal of the saline flush, a 2.5-ml sample was collected anaerobically into a heparinized arterial blood gas syringe, capped and immediately placed in an ice bath. Analysis was performed in duplicate within 20rain of collection using either a hemoximeter (Radiometer, model OSM2), or blood gas analyser (Ciba-Corning, model 278) which directly measured blood pH, partial pressures of oxygen and carbon dioxide (PO2, PCO2) and calculated further variables based on these measurements. The ideal alveolar gas equation was used to determine alveolar PO2 (PAO2) and PA-aO2 as described previously (Hopkins and McKenzie 1989). Both analysers were calibrated prior to the test sessions using standard solutions. Blood gas values were adjusted for deviations recorded in body temperature and pH due to exercise, according to procedures outlined previously (Dempsey et al. 1984; Kelman and Nunn 1966). Body core temperature was determined using a rectal probe positioned 12-cm past the anal sphincter and held in place during the P h y s i c a l c h a r a c t e r i s t i c s of the subjects used i n this s t u d y are s h o w n in T a b l e 1. T h e l/O2max values m e a s u r e d d u r i n g the p r e l i m i n a r y test were n o different f r o m those m e a s u r e d d u r i n g either the M A X or S M A X e x p e r i m e n t s . As expected, high p o w e r o u t p u t s were a c h i e v e d b y the athletes d u r i n g the exercise tests. All subjects c o m p l e t e d 4 r a i n at the M A X level a n d the m e a n time for the S M A X p r o t o c o l was 174 ( S E M 10)s. N o s u b j e c t was able to m a i n t a i n the S M A X exercise i n t e n s i t y (i.e. 115% l/O2max) for the full 4 rain; times r a n g e d f r o m 145 to 210 s. P e a k H R d u r i n g b o t h tests a v e r a g e d 189 ( S E M 3) b e a t s r a i n - 1 w h i c h was n o different f r o m t h a t m e a s u r e d d u r i n g the p r e l i m i n a r y i n c r e m e n t a l test to e x h a u s t i o n [ 1 9 t ( S E M 4) b e a t s . m i n - l l . T a b l e 2 o u t l i n e s the v e n t i l a t o r y r e s p o n s e s d u r i n g the two exercise tests. It s h o u l d be p o i n t e d o u t t h a t preexercise d a t a d o n o t reflect r e s t i n g levels since there were o b v i o u s l y c a r r y - o v e r effects f r o m the w a r m - u p i n 118 Table 1 Physical characteristics and performance attributes of subjects Variable Mean SEM Age (Year) Height (cm) Mass (kg) Maximal 02 uptake a (1'm i n - 1) Power output MAX (W) SMAX 22.9 179.0 73.4 4.77 1.9 1.5 2.3 0.19 365 421 15 18 Range 18 35 172.0 187.3 60.6 83.1 3.40 5.47 275-412 306-479 MAX, Intensity found to elicit maximal 0 2 uptake; SMAX, intensity estimated to require 115% of maximal O2uptake aMeasured during preliminary laboratory test addition to expected anticipatory responses. The data are important, however, since they allow relative changes during the exercise to be seen easily. In addition, they demonstrated that the subjects were beginning exercise in the same physiological state. Differences during exercise (MAX compared to SMAX) were found for all variables except aerobic power and ventilatory equivalent for CO2. Arterial blood gases assessed during the final 15 s of each exercise test are given in Table 3. The PaO2 and SaO2 decreased from pre-exercise to exercise conditions for both exercise intensities (P < 0.05). There was a difference in P,O2 between MAX and SMAX exercise intensity. The SaO2 ranged from 90.8%-95.4% during MAX exercise and from 91.8%-96.5% during the SMAX exercise. The differences between MAX and SMAX were also significant. When compared to the MAX test results all but two of the subjects had a rise in S~O2 during the SMAX test (Fig. 1), coincident with a significant elevation in I) E (15.71.min -1) from MAX to SMAX exercise. Individual partial pressure of arterial carbon dioxide (PaCO2) values during the two exercise tests are illustrated in Fig. 1. There were no differences in PaCOa Table 2 Ventilatory responses pre-exercise and during the two exercise conditions between exercise intensities (P = 0.96) although differences were obvious among subjects. Temperature and pH corrected PaO2 ranged from 11.3 to 14.2kPa (85.2-106.8 mmHg) during MAX to 11.6 to 14.3 kPa (87.4-107.5 mmHg) during the SMAX exercise. Temperature change during exercise averaged 0.5(SEM 0.06)°C (37.8-38.3°C) for the MAX and 0.4(SEM 0.07)°C (37.9-38.3 °C) for the SMAX exercise intensity. The PA_aO2 widened from pre-exercise to exercise under both conditions. The difference between MAX and SMAX exercise during the last 15 s was significant. Individual values ranged from 1.9 to 4.0kPa (14-30mmHg) during MAX and from 0.7-3.8 kPa (5-29 mmHg) during the SMAX intensity. There was a significant negative correlation between the level of PaO2 during exercise and the PA_aO2(Fig. 2). Table 4 shows the concentrations of various blood biochemicals pre-exercise and during the exercise tests. With the exception of blood pH and lactate concentrations there were elevations in all other chemical stimulants of I?E from MAX to SMAX exercise intensity. During MAX and SMAX exercise intensities respectively, individual concentrations ranged as follows; pH, 7.12-7.25 and 7.12-7.24; lactate, 8.5-20.1 and 9.1 21.0 retool'l- 1; K +, 6.4 7.7 and 7.1-8.1 retool'l- 1; noradrenaline, 23.2-93.9 and 35.1-114.6 nmol'l- 1 and adrenaline, 3.8-34.6 and 11.1-60.9 nmol.1-1. On average, plasma noradrenaline concentrations rose to about 19 and 23 times resting concentrations during MAX and SMAX exercise whereas adrenaline concentrations increased by 10 and 20 times, respectively. Flow-volume data were obtained on six subjects only. The results of the flow-volume analyses collected during the last 30 s of each test for the six subjects are summarised in Fig. 3. Tidal volume differed between the exercise conditions as did measured peak expiratory flow rate (PEFR). The differences in peak inspiratory flow rate (PIFR) measured during the SMAX test Variable O2 uptake (1-min 1) CO2 production (l'min-1) Pulmonary ventilation (1.min -1, BTPS) Pulmonary ventilation/O2 uptake Pulmonary ventilation/CO2 production Tidal volume (1) Respiratory frequency (breaths.min -1) MAX SMAX Pre-exercise Exercise Pre-exercise Exercise Mean SEM 0.53 0.11 0.62 0.05 Mean SEM 4.80 0.17 5.53 0.24 Mean SEM 0.62 0.18 0.68 0.61 Mean SEM 4.90 0.19 6.11 0.26 a 16.3 1.5 142.3 7.5 18.8 2.0 158.0 7.9" 30.7 1.3 30.5 1.0 29.6 1.3 32.2 1.3~ 26.3 1.0 1.31 0.09 25.7 1.3 2.97 0.12 27.6 0.7 1.49 0.12 25.9 1.5 2.83 0.13 a 12.4 48.2 12.6 55.8 2.6~ 1.0 1.9 1.2 BTPS, Body temperature and pressure, saturated. For other definitions see Table 1 ~Significant difference MAX versus SMAX exercise (P < 0.05) 119 Table 3 Blood gas values and alveolararterial difference in oxygen tension preexercise and during the two exercise conditions Variable MAX SMAX Pre-exercise Mean % 02 saturation 97.6 Partial pressure of arterial CO2 (kPa) 5.5 Partial pressure of arterial 02 (kPa) 14.9 Partial pressure of alveolar 02 (kPa) 15.2 Alveolar-arterial difference in partial pressure of Oz (kPa) 0.3 SEM 0.1 Exercise Pre-exercise Exercise Mean SEM 93.2 0.5 Mean SEM 97.6 0.2 Mean SEM 94.2 0.5 a 0.1 5.6 0.2 5.4 0.1 5.6 0.2 0.4 12.3 0.3 14.9 0.4 12.9 0.3" 0.2 15.4 0.2 15.3 0.3 15.8 0.1" 0.4 3.1 0.3 0.4 0.3 2.9 0.3" For other definitions see Table 1. aSignificant difference MAX versus SMAX exercise (P < 0.05) SaO. 97 (%) PaCO.z (kPa) 7.3 96 95 94 6.0 93 5.3 92 4.7 91 9 0 -MAX - 4.0 SMAX i r SMAX MAX Fig. 1 Individual arterial oxygen saturation (SaO2) percentages and arterial carbon dioxide tensions (PaCO2) measured during the final 15 s of each exercise test. For definitions see Table 1 A-aDO2 (kPa) 5.3 4.0 0 I MAX 0 SMAX r = -.77 0 0 00 1 ~ 0, ~ . ~~ 2.7 tion of peak expiratory reserve was used throughout the range of lung volumes naturally chosen during MAX exercise for subject A, while subject B did not appear to be as restricted during the same intensity. In spite of these differences, subject B regulated to a higher PaCO2 (and P,O2) during the MAX exercise test. The flow-volume loops for each minute over the duration of the exercise tests are also included. The figure demonstrates the expansion of the flow-volume loop as the exercise progressed, despite the constant exercise intensity. The 12E/1202 has been regressed against PaO2 (Fig. 5A) and PaCO2 (Fig. 5B) measured during both exercise tests. Figure 6 illustrates the significant relationship found between P,O2 and PAO2 in both exercise intensities. The relationship between arterial potassium concentration and corresponding I)E/I)O2 is shown in Fig. 7. (p<O.01) Discussion • 1,3 i 10.7 11.3 i 12.0 i i i i 12.7 13.3 14.0 14.7 PaO2 (kPa) Fig. 2 Relationship between partial pressure of alveolar O2-partial pressure of arterial 02 (PA .02) compared to PaOz during the two exercise tests compared to the MAX exercise intensity did not reach significance (P = 0.06). Figure 4 shows examples of two subjects who used different levels of expiratory and inspiratory flow reserve during both exercise intensities. A high propor- Previous authors have suggested that EIH may be due to a veno-arterial shunt (Powers and Williams 1987), an alteration in the shape of the oxygen dissociation curve in athletes (Rowell et al. 1964), significant ventilation-perfusion non-homogeneity (Gale et al. 1984) and/or less than optimal I)E (Miyachi and Tabata 1992). This study was primarily concerned with assessing the incidence and effect of a reduced 12E/1202 during intense exercise. We manipulated these parameters using an extreme exercise stimulus (supramaximal exercise) to determine whether we could alter 1#E to levels beyond those found under maximal conditions. We were also interested in identifying possible reasons for the reduced 12E/1202 observed in some athletes during periods of exceptional metabolic disturbance. Our results indicated that a significant level of arterial hypoxaemia (SaOz less than 93%) occurred in half of the 120 Table 4 Blood biochemistrypre-exercise and during the two exerciseconditions Variable MAX pH Lactate concentration (mmol'l t) K + concentration (mmol.l -~) Noradrenaline concentration (nmol.1-1) Adrenaline concentration (nmol'I- 1) SMAX Pre-exercise Exercise Pre-exercise Exercise Mean SEM 7.39 0.01 Mean SEM 7.18 0.01 Mean SEM 7.39 0.01 Mean SEM 7.19 0.02 1.1 0.2 12.9 1.2 1.4 0.3 13.5 1.3 4.4 0.1 6.8 0.1 4.4 0.1 7.7 0.1a 2.6 0.3 49.9 6.1 2.6 0.2 59.2 7.6 a 1.7 0.3 16.4 2.7 1.7 0.2 33.5 5.9a For definitionssee Table 1 aSignificantdifferenceMAX versus SMAX exercise(P < 0.05) is 1 12 PEFR (i.sec-~) 9 PIFR (I.sec "1) 9 ,21 ~ 4 ~ i i VOLUME (L) Fig. 3 Summary of the group mean (n = 6 subjects) ventilatory responses under voluntary conditions and during the two exercise tests. Values were as follows: forced vital capacity 5.38 (SEM 0.5); tidal volume MAX 2.90 (SEM 0.2), SMAX 2.75 (SEM 0.2); peak expiratory flow rate (PEFR) (1.s- 1) voluntary loop 12.5 (SEM 1.0); MAX 8.21 (SEM 0.7), SMAX 9.65 (SEM 0.7); peak inspiratory flow rate (PIFR) (1.s- ~) voluntary loop 9.68 (SEM 0.5); MAX 7.62 (SEM 0.6), SMAX 8.58 (SEM 0.4). For other definitions See Table 1 subjects exercising at intensities corresponding to 1202max and 30% of the subjects during the supramaximal intensity (115% l)O2max). When the exercise intensity was increased from maximal to supramaximal levels, all but two of the subjects elevated 12E with a concomitant attenuation in the degree of hypoxaemia. This occurred in spite of the fact that there was greater oxygen demand for both the exercise and respiratory work. Regression analyses indicated that PaO2 during exercise was positively correlated with the level of JTE/[')O2 as well as negatively correlated with PA-aO2. Although cause and effect cannot be estab- lished, the results would suggest that both 19E/120a and a widening gradient for 02 across the lung (perhaps as a result of the lower I/E) contributed to the reduction in PaO2. These results, together with analysis of respiratory flow-volume data recorded during rest and exercise indicate that the potential to ventilate further was present during the MAX exercise intensity; however, the subjects chose not to, despite lower levels of SaO2. This study has therefore demonstrated that an exercise stimulus was important for further 1/E when moving from the maximal to the supramaximal power output. The widening of P A - a O 2 and the decrease in SaO2 from rest to exercise confirmed recent findings and would support the view that the pulmonary system may limit performance in a significant number of elite level athletes (Dempsey et al. 1989; Hopkins and McKenzie 1989; Powers et al. 1989b; Williams et al. 1986). Previous reports have indicated SaO 2 levels may reach as low as 84%-86% during exercise (Powers et al. 1984, 1988; Williams et al. 1986). The minimal individual value of 90.8% SaO2 found in the present study was not as extreme as many of these earlier reports. Many studies reporting such low values have used indirect pulse oximetry to assess arterial oxygenation and there have been mixed reports concerning the appropriateness of this technique during severe exercise (Norton et al. 1992; Powers et al. 1989a,). Notwithstanding these limitations, differences in the type of exercise may also account for part of this discrepancy since directly measured S,O2 values have been as low as 85% during treadmill running (Rowell et al. 1964). An important finding in the present study was the greater 02 transfer during SMAX exercise (compared to the MAX intensity), achieved by elevating alveolar pressure through increments in ~;'E (Table 3). A small [0.4 kPa (2.7 mmHg)] but significant rise in P A O 2 occ u r r e d in association with a mean increase of 15.7 1.rain-1 in I?E (Tables 2, 3). The P a O 2 w a s elevated by an average of 0.6 kPa (4.7 mmHg) and S~O2 by 1% during exercise at the higher intensity. The significant 121 SUBJECTA 15 15 IZ 12 PEFR PEFR (i.se61) 9 (I.sed 1) 6 PIFR (I.sec "~ ) 9 6 PIFR 6 6 (I.sec "1 ) 1in-1 9 9 12 12 4 3 2 1 VOLUME (k) t 4 2, 2 1 VOLUME (L) SUBJECT B PEFR (i.sec-1) PIFR 15 15 12 12 PEFR (i.sec-1) 9 9 6 6 3 3 0 0 3 3 s PIFR s (I.sec "1 ) (I.see 1 ) 9 12 9 5 4 3 2 1 0 VOLUME (L) 1_2 5 4 3 2 1 o VOLUME (L) Fig. 4 Ventilatory responses for two subjects (A and B) during the two exercise tests. Relevant ventilatory and blood biochemistry data for each subject are also given for reference (see text for discussion). 12E, Pulmonary ventilation; for other definitions See Table 1 and Figs. 1 and 2 relationship between PAO2 and PaO2 during the exercise tests would suggest alterations in PAO2 may be important in determining corresponding changes PaO2 during exercise. It should be pointed out that despite an elevated SaO2 during the SMAX exercise intensity there was no measured increase in 1202. It is likely the additional 02 delivered in the circulation (estimated at about 60 ml with a 1% increase in S~O2) was outside of the resolution of our measurements for whole-body 1702. Overall, it has been demonstrated in the present study that elevations in 12E during the supramaximal exercise were associated with increased PAO2 and PaO2, and with a small reduction in Pa-aO2 . The question then arises as to why the majority of subjects tolerated the decreased %SaO2 during exercise and chose not to elevate I~E? This was particularly pertinent under conditions of the MAX test. Several potential causes of the reduced l)'E/12Oz have been proposed. These have included a mechanical limitation to ventilate further at the lung volumes naturally chosen during exercise (Johnson et al. 1992), respiratory muscle fatigue (Aaron et al. 1992; Gallagher and Younes 1989; Johnson et al. 1992; Levine and Henson 122 Fig. 5 Relationship between an indicator of relative ventilation (ventilatory equivalent for oxygen; pulmonary ventilation/oxygen uptake, 1)E/1202) and arterial oxygen tension (P,O2; A) and between 12E/1202 and arterial carbon dioxide tension (PaCO2; B) during the two exercise tests. For other definitions See Table 1 ~/E/%/02 45 40 ~/E/~702 45 A r = .71 (p<O.01) O 30 25 • 1 2.0 PaO 2 (kPa) 14.7 2/ ../ o 1 2.0 (p<O.O1) • MAX o SMAX 10.7 i 13.3 14.7 16.0 17.3 PAOz(kPa) Fig. 6 Relationship between arterial oxygen tensions (PaO2) and alveolar (PAO2) during the two exercise tests. For other definitions See Table 1 VE/V02 45. O 40 35 30 • .;.o oo; o r=53 25 • MAX o SMAX 20 6.0 615 " ' , , . ~ e _~ _ •• •00 0 • MAX o SMAX o O ~ 25 ~ 2.7 1 3m3 PaOz (kPa) • (p~O.01) , 20 l I .~ 10.7 / r = -.79 30 20 13.3 40 35 B 0 71s 810 81s 91o [K +] (mmol.Iq) Fig. ? Relationship between ventilatory equivalent for oxygen ([2E/1/O2) and arterial potassium concentration [K +] recorded during the final 15 s of both M A X and SMAX exercise conditions. For definitions See Table 1 and Fig 5 1988) and differences among subjects in their ventilatory response to a given level of metabolic stimuli (Cerretelli and di Prampero 1987; Johnson et al. 1992). Recently, it has been suggested that a mechanical limitation to l)'~ is the primary reason for a constraint of 1410 1417 4.0 4.7 5.3 6.0 6.7 73 PaCO2 (kPa) the hyperpnoeic response during heavy and maximal treadmill exercise (Johnson et al. 1992). These authors have shown that inducing either hypercapnia or greater hypoxaemia during maximal exercise failed to increase I/E, inspiratory or expiratory pressure in the majority of their subjects, although several individuals did show a moderate elevation in 1/~. In contrast, McParland et al. (1991) have demonstrated an elevation in I?E during maximal exercise with increased dead space loading. The results of the present study indicated that the subjects operated to increase I?E from the MAX to the SMAX exercise intensity by augmenting respiratory frequency (fR) and slightly decreasing tidal volume (Vr) (Table 2). The potential to increase 17E further, therefore, existed during all exercise intensities, yet this option was not adopted, at the expense of arterial blood gas homeostasis. Although a mechanical limitation to VE was shown to be absent among the subjects in this study, the results do not explain why a greater ventilatory response was not achieved during the MAX exercise intensity. Such an increase in I) E (for example, to the same level as that found during the SMAX test) would presumably have attenuated the degree of hypoxaemia. The respiratory flow-volume analyses in the present study failed to show any clear association between the levels of SaO 2 o r PaO2, and the fraction used of the potential flow-volume area, forced vital capacity (FVC) or PIFR and PEFR. Although there was a range in the fraction of FVC chosen as VT during exercise (MAX, 42%-70% and SMAX, 41%-60%), typically this was substantially less than 70% of FVC and consistent with previous reports (Whipp and Pardy 1986). Similarly, analysis of the final 30 s of exercise flow-volume loops revealed a range in flow rates (as a fraction of the maximum possible generated voluntarily at a given lung volume) for both the inspiratory (MAX, 63% 86% and SMAX, 71%-96%) and expiratory manoeuvres (MAX, 54%-81% and SMAX, 55%-89%). This simplistic approach may be somewhat misleading since most athletes did approach their maximal ability to generate flow throughout at least part of their 123 expiratory effort (Fig. 3). It should be pointed out however, that these high flow rates were only seen during the final minute or so of the exercise tests (for example see Fig. 4). The subjects tested by Johnson et al. (1992) were often found to exhibit a mechanical limitation of lung and respiratory muscle for producing alveolar ventilation. However, we did not find that those of our subjects who suffered the greatest hypoxaemia also demonstrated the greatest expiratory flow limitation. Two examples of individuals who displayed variable levels of expiratory and inspiratory flow limitation are presented in Figure 4, together with indices of blood gas status during exercise. Despite the potential for loss of resolution by visually estimating the mean flow-volume loop over each collection period, it is clear that during the MAX test at least, only subject A was encroaching upon his voluntary capacity for flow generation at about mid-tidal volume. Each minute of exercise also resulted in a reduced 'reserve' for flow generation in both subjects. Thus, differences in blood gas status during exercise would not appear to be explained on the basis of possible mechanical constraints only since subject A had a lower PaCO2. Research concerning the possibility of respiratory muscle fatigue during exercise has suggested that inspiratory muscle fatigue either does not occur or has no functional significance during intense exercise of short duration (Bye et al. 1983; Coast et al. 1990; Gallagher and Younes 1989; Johnson et al. 1992; Levine and Henson 1988). This study provided support for this opinion during events of 4 rain or less. There have been differing thoughts concerning the potential for training-induced adaptations in peripheral chemosensitivity (Cerretelli and di Prampero 1987; Johnson et al. 1992; Saunders et al. 1976; Scoggin et al. 1978). Of particular significance in this study was the range in P~CO2 among the subjects during exercise [MAX, 4.8-6.9kPa (35.9-51.7mmHg) and SMAX, 4.2-6.5 kPa (31.7-48.6 mmHg)]. The consistency within subjects to regulate to a particular individual PaCOz in the two exercise intensities (while PaO2 and SaOz varied) was apparent (Fig. 1). The reason for some subjects tolerating high P,CO2 during exercise (particularly MAX intensity) is not known). When the data for both conditions were combined (n -- 20), there were significant correlations between P~CO2 (r = 0.79) and PaO2 (r = 0.71) levels and I)z/l)'02 during exercise (Fig. 5A, B). Thus, greater ventilatory responses were associated with lower P,CO2 and higher PaO2. Although these significant relationships (and those of Fig.6) are clearly shown in the present study, there are inconsistencies in the literature. For example, Powers et al. (1992) have not found any significant relationship between PAO2 and P~O2 in their subjects exercising to maximal levels on a cycle ergometer. Furthermore, they have reported no relationship between 12E/1202 and PaO2 or PaCO2 at maximal exercise intensity, suggesting that reduced 12E/1202 played an insignificant role in the development of EIH. In support of the present findings, however, Miyachi and Tabata (1992) have obtained similar results to those of the present study such as a significant correlation between l)'z/l)'02 and SaO2 of 0.74 (0.87 in the present study). They have concluded that the relatively low ventilatory response may account for about 50% of the arterial 02 desaturation in exercise. It is not known why these differences have arisen. One possibility may be the relative homogeneity of the subjects with respect to their training in the study of the Powers et al. (1992) (compared to the other two groups) which decreased the spread for the variables assessed. One possibility for differences in the ventilatory response among individuals in this study could be related to differences in responses to the same level of biochemical stimulation and/or variations in the concentrations of chemoreceptor stimulants during exercise (Cerretelli and di Prampero 1987; Johnson et al. 1992; Miyachi and Tabata 1992). For example, in the study by Miyachi and Tabata (1992) a significant positive relationship has been found between S~O2 during maximal exercise and the subjects' ventilatory response to hypercapnia at rest. The moderate association (r = 0.53) found between [K +] and (/z/l/02 during the two exercise conditions (Fig. 7) shows at least one possible explanation for the greater ventilatory drive in some subjects. It is not known why [K ÷] would vary among subjects during exercise to the extent found in this study [and independently of absolute exercise intensity and estimated muscle mass (estimated as a constant fraction of body mass; kg)], however, previous reports have shown Na+-K ÷ pump activity to be influenced by training (McKenna et al. 1993). When compared to the MAX intensity, the elevated 12~ during the SMAX intensity was likely to have been in response to the influence of more extreme levels of stimulants such as K + and catecholamines (Table 4) during the supramaximal exercise test which would undoubtedly have exacerbated ventilatory drive (Wasserman et al. 1986). Greater afferent stimuli from the exercising muscles generating larger forces could also have contributed to the enhanced ventilatory drive (McClosky and Mitchell 1972). Since l/Oz did not change from MAX to SMAX, the COz production must have also been similar. The increased elimination of CO2 during the SMAX exercise, with the same measured PaCO2, may have been due to a reduced time for CO2 to diffuse completely into the fluid compartments of the body. The significant lowering of PaO2 and SaO2 during the experiments would seem to suggest the exercise protocol may also be important, in particular the intensity and duration of the test. Early phases of the exercise period have been shown to be associated with accumulation of body CO2 stores which are far greater than for 02 (Wasserman et al. 1986). Thus, ventilatory drive has been found to be relatively sluggish at this time (Fig. 4), in spite of rapidly lowered PaO2 and PAO2 (Hopkins and McKenzie 1989). Since it has previously been shown that 12z lags behind rather than leads 124 I/CO2 in response to exercise (Wasserman et al. 1986), it would be expected that CO2 stores would stimulate 1)E earlier (faster VE kinetics) during SMAX exercise (Ward et al. 1983). In this way it may have been too late to catch up with the required ventilatory response during the MAX exercise intensity (which was stopped at 4 min). In summary, this study demonstrated that high!y trained and motivated athletes were able to increase VE when power output was increased from maximal to supramaximal levels of intensity. That is, there does not appear to have been a mechanical constraint to ventilation at maximal exercise levels in the subjects participating in this study. As a consequence of this elevation in VE arterial blood gas status was affected during the more intense exercise test. Specifically, less extreme levels of arterial hypoxaemia were found during the more severe exercise intensity since the majority of subjects increased 1/E. The precise mechanism operating to constrain the ventilatory effort during the lower exercise intensity is still unknown. However, the ventilatory response during severe exercise is the net result of a combination of many stimuli, including both neural and humoral factors. It has been suggested that these must be integrated to produce the most effective possible mechanical response (Johnson et al. 1992; Wasserman et al. 1986), presumably with the lowest energy cost, in the face of dramatic blood biochemistry shifts. 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