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J Appl Physiol 95: 1623-1631, 2003. First published July 3, 2003; doi:10.1152/japplphysiol.00415.2003
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Facial cooling-induced bradycardia does not slow pulmonary O2 kinetics at the onset of high-intensity exercise

Masako Endo,1 Shinko Tauchi,1 Naoyuki Hayashi,2 Shunsaku Koga,3 Harry B. Rossiter,4 and Yoshiyuki Fukuba1

1Department of Exercise Science and Physiology, School of Health Sciences, Hiroshima Prefectural Women's University, Hiroshima 734-8558; 2Laboratory of Exercise Physiology, Faculty of Health and Sport Sciences, Osaka University, Toyonaka 560-0043; 3Laboratory for Applied Physiology, Kobe Design University, Kobe 651-2196, Japan; and 4Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, California 92093

Submitted 25 April 2003 ; accepted in final form 2 July 2003


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 DISCLOSURES
 REFERENCES
 
The mechanism(s) underlying the attenuation of the slow component of pulmonary O2 uptake (O2) by prior heavy-intensity exercise is (are) poorly understood but may be ascribed to either an intramuscular-metabolic or a circulatory modification resulting from "priming" exercise. We investigated the effects of altering the circulatory dynamics by delayed vagal withdrawal to the circulation induced by the cold face stimulation (CFS) on the O2 kinetics during repeated bouts of heavy-intensity cycling exercise. Five healthy subjects (aged 21-43 yr) volunteered to participate in this study and initially performed two consecutive 6-min leg cycling exercise bouts (work rate: 50% of the difference between lactate threshold and maximal O2) separated by 6-min baseline rest without CFS as a control (N1 and N2). CFS was then applied separately, by gel-filled cold compresses to the face for 2-min spanning the rest-exercise transition, to each of the first bout (CFS1) or second bout (CFS2) of repeated heavy-intensity exercise. In the control protocol, O2 responses in N2 showed a facilitated adaptation compared with those in N1, mainly attributable to the reduction of slow component. CFS application successfully slowed and delayed the heart rate (HR) kinetics (P < 0.05) on transition to exercise [HR time constant; N1: 55.6 ± 16.0 (SD) vs. CFS1: 69.0 ± 12.8 s and N2: 55.5 ± 11.8 vs. CFS2: 64.0 ± 17.5 s]; however, it did not affect the "primary" O2 kinetics [O2 time constant; N1: 23.7 ± 7.9 (SD) vs. CFS1: 20.9 ± 3.8 s, and N2: 23.3 ± 10.3 vs. CFS2: 17.4 ± 6.3 s]. In conclusion, increased vagal withdrawal delayed and slowed the circulatory response but did not alter the O2 kinetics at the onset of supra-lactate threshold cycling exercise. As the facilitation of O2 subsequent to prior heavy leg cycling exercise is not attenuated by slowing the central circulation, it seems unlikely that this facilitation is exclusively determined by a blood flow-related mechanism.

vagal activation; oxygen uptake adjustment; heavy exercise

PULMONARY OXYGEN UPTAKE (O2) during "moderate-intensity" square-wave cycling exercise [i.e., for work rates below the lactate threshold (LT)] approaches its steady state with an exponential time course (phase II) after a short delay (phase I) and attains a steady state (phase III) within 2-3 min in normal healthy individuals (e.g., see Whipp and Ward (53) for review). It has been suggested that the time constant ({tau}) for phase II O2 during moderate exercise reflects that of muscle O2 (mO2) (17), and, because it is also closely related to intramuscular phosphocreatine concentration, "metabolic inertia" is thought to be its primary determinant (7, 35, 42). An alternative to this view argues that O2 kinetics during moderate-intensity exercise is determined by a vascular limitation of O2 delivery [e.g., see Hughson (25) for review].

During "heavy-intensity" exercise (i.e., for supra-LT work rates), however, the O2 response is more complex. The response consists of two main components: a fundamental phase II component, still well described by a single-exponential, and a subsequent delayed phase yielding a slowly developing supplemental rise in O2, which has been termed "excess" O2 or the O2 "slow" component (52). Consequently, this delayed O2 slow component supplements the expected increase in O2, projected from the sub-LT O2-work rate relationship (e.g., Ref. 12).

Although the physiological determinant(s) of the O2 response during square-wave exercise in the supra-LT domain is (are) still currently debated (e.g., Refs. 14, 27, 40, 48), it has been suggested that O2 delivery may be of a greater importance in modulating the O2 kinetics during heavy-intensity exercise than during moderate-intensity work rates (13, 31, 53). Support for this notion is, in part, derived from the demonstration that the O2 kinetics may be modulated (speeded) when heavy-intensity exercise (usually cycling) is preceded by a "priming" bout of identical intensity (13, 32, 44). For normal healthy subjects, such a modulation may only be brought about during exercise in the heavy-intensity domain and not in the moderate domain. It was proposed that this kinetic adjustment of O2, seen on the transition to a second exercise bout, may be due to improved muscle perfusion consequent to the vasodilatory effects of the residual lactic acidemia still present at the onset of the second bout (13). More direct support for the circulatory limitation hypothesis is evident where central and/or peripheral circulation has been modified by postural manipulation (28), prior sprint exercise (47), administration of {beta}-adrenergic blocker (25, 39), and hypoxic or hyperoxic air inspiration (32), the latter causing the mean response time of O2 to be speeded in the heavy-intensity domain and not in the moderate-intensity domain. However, the alternative view, i.e., the metabolic inertia hypothesis, has also been supported by similar experimental manipulations, such as lower body negative pressure (55), and a reactive hyperemic maneuver (50), which had no effect on the O2 kinetics. Therefore, it is currently not clear whether O2 delivery to the exercising tissues is a critical determinant of the O2 response dynamics during heavy intensity exercise.

It is well known that cold facial stimulation (CFS) induces a bradycardia through the trigeminal-vagal-cardiac pathways (e.g., Ref. 29). It is hypothesized, therefore, that CFS during the transition to a square-wave increase in cycle ergometer work rate would cause O2 delivery to be delayed consequent to a delayed circulatory response via increased vagal tone. Although determination of O2 delivery is technically challenging during cycle ergometry, and was not measured in the present study, CFS has been shown to lead to an immediate reflex bradycardia (19) followed by a sympathetically mediated vasoconstriction occurring after ~40 s of CFS (20). This increase in muscle sympathetic nerve activity (9) results in increased mean arterial pressure (e.g., Ref. 5) and a reduction of peripheral flow measured either in the finger, toe, and calf (19) or the limb (20) but not in the brain (5). As such, if the speeded O2 response during the second exercise bout of a repeated-bout protocol (cf. Ref. 13) is predominantly due to a more rapid circulatory adaptation (and, therefore, O2 delivery), then application of CFS at the onset of the second exercise bout would be expected to offset, or even delay, the adaptation of O2. We, therefore, investigated the effects of delayed vagal withdrawal (via CFS) on the O2 kinetics at the onset of heavy-intensity exercise, both before and after a heavy-intensity exercise bout.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 DISCLOSURES
 REFERENCES
 
Subjects. Eight subjects volunteered for the study, were found to be in a good state of health by a physician, and gave informed consent to participate as approved by the ethics committee of the local institution (in accordance with the Declaration of Helsinki). Each subject underwent a series of preliminary CFS tests at rest, before performing the main protocol. During these preliminary tests, we found that two subjects could not tolerate the feeling of discomfort during CFS and another subject did not show a bradycardiac response. Therefore, five subjects [3 women and 2 men; age 28 ± 10 (SD) yr, height 168 ± 7 cm, weight 63 ± 13 kg] finally proceeded to the exercise protocols.

Exercise protocols. The subjects initially performed a ramp-incremental exercise test to their limit of tolerance, at a rate of 12 W/min (for the female subjects) or 16 W/min (for the male subjects), on an electromagnetically braked cycle ergometer (232c-XL, Combi) at 60 rpm. During the incremental exercise, ventilatory and gas-exchange parameters were measured breath by breath, and capillary blood was sampled every 2 min for blood lactate determination (see details below). The V-slope method (3) was used to determine the LT, with concomitant corroboration from the onset of systematic increases in the ventilatory equivalent for O2 (minute ventilation/O2) and end-tidal PO2, without a concomitant rise in the ventilatory equivalent for CO2 output (minute ventilation/CO2 output) or fall in end-tidal PCO2 (51). Noninvasive determination of the LT was further corroborated in the profile of capillary blood lactate concentration. The work rate for the subsequent square-wave exercise was then set at {Delta}50%, where {Delta} is the difference between the work rates associated with LT and maximal O2 from the incremental-ramp test (the delay time between work rate and O2 was accounted for by the standard procedure; Refs. 36, 54).

The subjects then completed three different cycle ergometry exercise protocols in the upright position: two "repeated" bouts of a 6-min square-wave exercise separated by 6 min at rest and one "single" bout of 6-min square-wave exercise (Fig. 1). The protocols were preceded by 3 min of rest, and the work rate during the 6-min bouts was set at {Delta}50%. Subjects maintained a constant pedaling rate of 60 rpm throughout the exercise. For CFS, a soft gel-pack (14 x 30 cm) refrigerated to ~0-3°C was applied to the forehead and eyes [the most sensitive area for this reflex (29)] from 1 min before to 1 min after the onset of the exercise. A total duration of 2 min of CFS was chosen as being close to the limit of tolerance for most subjects (19). The subjects performed the first (N1) and second (N2) exercise bouts without CFS (control trial) (Fig. 1). CFS was then applied at either 1) the onset of the first exercise bout (CSF1) or 2) the onset of the repeated (second) exercise bout (CSF2). Each subject performed all three conditions in a randomized sequence. When CFS was applied at the onset of the first exercise bout (CFS1 trial in Fig. 1), the subject performed a single bout only. Room air was kept at 24 ± 1°C by a thermal feedback device. Each subject repeated all three protocols on at least three occasions at the same time on different days. Only one test was performed on a particular day, and each exercise was separated by at least 48 h.



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  		Fig. 1. Schematic representation of the 3 experimental protocols. Control trial is a repeated-bout (1st bout, N1; 2nd bout, N2) square-wave exercise test separated by 6-min rest. Cold face stimulation (CFS) was applied either at the onset of a single-bout exercise (CFS1) or at the onset of the repeated exercise bout (bout 2: CFS2). CFS was applied from 1 min before to 1 min after the onset of exercise. {Delta}50%, 50% of the difference between lactate threshold and maximal O2 uptake.

 

Measurements. Ventilatory and gas-exchange responses were determined breath by breath by using a computerized metabolic measuring system (model RM-300, Minato Medical). Before each exercise test, a hot-wire flow-sensor and gas analyzers were calibrated by inputting a known volume of air (at several mean flow rates) and gas mixtures of known concentration, respectively. The heart rate (HR) was monitored by cardiotachogram (model BP-306, Colin). A second-by-second time course was calculated for each variable by interpolation and then stored on disk for further analysis. Capillary blood was sampled from a heated fingertip (heated with a soft-gel pack) just before the onset and just after the cessation of each exercise bout for the determination of lactate by an enzymatic method (HEK-30L, Toyobo).

Estimation of O2 and HR response. The O2 and HR responses to heavy-intensity exercise were quantified by a cluster of empirical and model-based indexes during both the first and second 6-min square-wave bouts (i.e., N1, N2, CFS1, or CFS2). In all cases, the preexercise (or pre-CFS) baseline was taken from the average of 2 min before exercise. The initial 20 s after the onset of exercise (phase I) was eliminated from any fitting procedure (54). Two models were fit to the responses expressed as

(1)
where f(t) is the O2 or HR at time t; BL is the baseline value of rest; and A, Td, and {tau} are the amplitude, time delay, and time constant parameters, respectively (where p and s represent primary component and slow component, respectively; see below). In the first instance, the second exponential term of Eq. 1 was set to zero and the whole response (excluding phase I) was considered. This allowed conventional estimation of {tau} for HR (providing a broad description of HR dynamics, by using {tau} as a "parameter of convenience") and the "effective" or mean response time of O2 to be established (effective {tau}). The increment in O2 between minutes 3 and 6 of the 6-min exercise bout [{Delta}O2(6-3)] was also measured to estimate the magnitude of the O2 slow component empirically.

Because it has been shown that there is a bias in the O2 residual resulting from a monoexponential fitting procedure during supra-LT exercise (due to the influence of the slow component; e.g., Refs. 2, 6, 37), the same O2 data were also fitted with Eq. 1 where the second term was allowed to be freely variable, i.e., a double-exponential incorporating two amplitudes [primary (Ap) and slow (As) components], two time constants [primary ({tau}p) and slow ({tau}s) components], and two time delays [primary (Tdp) and slow (Tds) components]. Fitting was performed by using a nonlinear least-squares regression technique (Marquardt-Levenberg Algorithm in Sigma Plot 2000, Jandel Scientific). The slow component amplitude is reported as the difference between the Ap asymptote and O2 at the end of exercise (defined as A2'), rather than the extrapolated asymptotic value for As (similar to Refs. 1, 10, 30).

Statistics. The values are expressed as means ± SD. Differences between conditions (i.e., to ascertain the effects of bout number and the effect of CFS imposition independently) were initially evaluated by repeated-measures ANOVA (SPSS for Windows, SPSS); the differences in the parameters were then evaluated by two-way repeated-measures ANOVA (by protocol, i.e., N1, N2, CFS1, and CFS2). When a significant difference was detected, this was further examined by Tukey's post hoc test. Statistical significance was accepted at P < 0.05.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 DISCLOSURES
 REFERENCES
 
Effects of CFS and bout repetition. The initial broad description of the effects of CFS imposition revealed a significantly longer (P < 0.05) time delay of both the HR (Td) and O2 (both Td from the monoexponential fit, and Tdp) consistent with a significant slowing of central cardiac output and peripheral blood flow, independent of bout number. Time-averaged HR responses of a representative subject and group means are presented in Fig. 2. These data demonstrated a significantly slowed (i.e., longer {tau}) and delayed (i.e., longer Td) HR response mediated by CFS at the onset of both exercise bouts. The effect of the repeated bouts protocol (i.e., bout 1 vs. bout 2, independent of CFS) was also characterized by an alteration in the Td, as a reduction in Td of HR and O2. However, the predominant effects were manifest in an increase (P < 0.05) in the effective {tau} of O2, and a reduction (P < 0.05) of A2' and O2(6-3). After the establishment of significant (P < 0.05) alterations in the HR and O2 responses by CFS and the repeated-bouts protocol, the interaction of these effects were then explored in detail.



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  		Fig. 2. Heart rate response at the onset of the 1st bout (top) and 2nd bout (bottom) with (thick lines) and without (thin lines) CFS application in a representative subject (A) and averaged group mean (B; i.e., from all subjects). Residuals show the difference between control and CFS application (plotted in the bottom of each panel as a dotted line). CFS application (i.e., disturbance of vagal withdrawal), therefore, clearly had a substantial effect on the dynamics of the central circulation.

 

N1 vs. N2. An example of the O2 responses for a representative subject and the group means to the repeated-bout control protocol are superimposed in Fig. 3. The first bout of supra-LT leg cycling exercise induced an adaptation of the subsequent O2 response during the identical second exercise bout. Although monoexponential fitting (i.e., effective {tau}) illustrated this difference in O2 kinetics between N1 (43.8 ± 11.8 s) and N2 (27.5 ± 8.0 s) (Table 1), double-exponential fitting demonstrated no difference in {tau}p (N1: 23.7 ± 7.9 vs. N2: 23.3 ± 10.3 s). Thus the predominant effect of the first bout was to significantly reduce the slow component [{Delta}O2(6-3), N1: 145 ± 73 vs. N2: 63 ± 25 ml/min; and A2', N1: 298 ± 140 vs. N2 101 ± 31 ml/min]. Ap was not significantly affected (N1: 1,749 ± 533 vs. N2: 1,830 ± 522 ml/min) by prior exercise but was manifest from a significantly increased baseline O2 during N2 (365 ± 92 ml/min) compared with N1 (260 ± 47 ml/min).



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  		Fig. 3. Superimposition of the oxygen uptake responses to their relevant control bouts in a representative subject (A) and averaged group mean (B; i.e., from all subjects). Top, control trial N1 (line) vs. N2 ({circ}); middle, control trial N1 (line) vs. CFS1 ({circ}); bottom, control trial N2 (line) vs. CFS2 ({circ}). Plot of O2 uptake is averaged every 10 s.

 

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  		Table 1. Pulmonary O2 response characteristics during N1, N2, CFS1, and CFS2

 

CFS1 vs. N1 and CFS2 vs. N2. As expected, HR was dramatically decreased during CFS manipulation at the onset of both the first and second bouts (Fig. 2). The residual plot (i.e., the difference of HR between the CFS and control protocols; Fig. 2, bottom) clearly demonstrated a large CFS-induced depression of HR. This substantial effect was maintained between ~30 s before and 60-90 s after exercise onset (e.g., average HR; N1: 80.0 ± 7.0 vs. CFS1: 71.8 ± 1.6 and N2: 105.1 ± 9.7 vs. CFS2: 93.3 ± 12.4 beats/min at the onset of exercise; N1: 123.7 ± 14.5 vs. CFS1: 111.4 ± 8.2 and N2: 138.5 ± 12.6 vs. CFS2: 124.0 ± 11.9 beats/min at 30 s after onset). The HR kinetics (i.e., {tau} HR) after the onset of exercise was significantly increased by CFS in both the first (N1: 55.6 ± 16.0 vs. CFS1: 69.0 ± 12.8 s) and second bouts (N2: 51.5 ± 11.8 vs. CFS2: 64.0 ± 17.5 s) (Table 2).


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  		Table 2. Heart rate response characteristics during N1, N2, CFS1, and CFS2

 

O2 responses (both from a representative subject and the group mean) during the first exercise bout after CFS manipulation (CFS1) is shown in Fig. 3 and superimposed with the control N1 response. Interestingly, the O2 response was unaffected by the CFS manipulation during the first bout as determined by all the quantitative variables derived from either empirical or monoexponential- and/or double-exponential fitting (Table 1). Surprisingly, however, there were also no changes in the dynamics of the O2 response during the second exercise bout (CFS2) compared with N2 (Fig. 3, Table 2). As such, CFS did not discernibly affect the effective {tau} or {tau}p of O2 at the onset of supra-LT exercise despite the blunted HR responses.

Blood lactate concentrations just before the onset of exercise of bouts N1, N2, CSF1, and CSF2 were 0.9 ± 0.2, 5.1 ± 0.7, 1.0 ± 0.3 and 5.6 ± 0.8 meq/l, respectively. The prior exercise bout significantly increased blood lactate concentration; however, CFS during either the first or second exercise bouts had no further effect (i.e., no differences were observed between end-exercise N1 vs. CFS1 or N2 vs. CFS2). Also, blood lactate concentration accumulation (i.e., the difference of lactate concentration before, and after, the exercise bouts) was not significantly affected by the CFS manipulation (N1: 5.0 ± 0.6 vs. CFS1: 4.5 ± 1.2, and N2: 1.1 ± 0.6 vs. CFS2: 1.9 ± 0.9 meq/l).


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
DISCLOSURES
 REFERENCES
 
The main finding of this study was that facial cooling-induced bradycardia at the onset of square-wave heavy-intensity leg cycling exercise had no descriminable effect on pulmonary O2 kinetics. This was the case during both the first transition, where blood flow is thought to be potentially limiting (e.g., Ref. 32), and also during the second, repeated bout, where a speeded limb blood flow has been suggested to mediate the speeding of the O2 dynamics (e.g., Refs. 13, 47). In this study, the time course of HR was demonstrably slowed in response to an interruption of vagal withdrawal and increased sympathetic tone by CFS, both before and after the onset of exercise. Despite the substantially slower and delayed HR kinetics, the O2 kinetic parameters estimated by mono- and double-exponential models were not significantly affected by the CFS manipulation in either heavy-intensity exercise bout. These findings are consistent with the notion that a reduction in the circulatory dynamics does not appear to play a central role in the adjustment of pulmonary O2 during high-intensity leg cycling exercise (at least up to {Delta}50%). This conclusion, however, assumes that blunting the circulatory response via CFS would be transmitted to the periphery as a significant reduction in muscle O2 delivery. Each of these interpretations are addressed in turn.

Does CFS limit limb blood flow? During resting conditions, CFS manipulation is well known to induce an immediate and pronounced bradycardia coupled with a delayed rise in systemic blood pressure (e.g., Refs. 5, 45) and is commonly used to assess autonomic function (e.g., Ref. 19). The autonomic nervous system is one of the factors that can influence O2 transport (25) because of its controlling influence on cardiac activity via the balance of sympathetic and parasympathetic tone. In this study, the CFS manipulation was applied for 2 min, around the onset of exercise, to activate vagal tone (via reflex centers located in the medullar region; Ref. 19) and induce a pronounced bradycardiac response at rest before the onset of exercise and an attenuated tachycardia after the onset of exercise. This was clearly seen in our subjects (Fig. 2, Table 2). Whereas parasympathetic and sympathetic activity seem to be reciprocal, parasympathetic tone apparently does not affect vascular tone, because human arterioles show no evidence of parasympathetic innervation. Therefore, it is likely that the disturbance of vagal withdrawal mainly induces a negative effect on central circulatory acceleration (i.e., an attenuated increase of HR and cardiac output). However, CFS is also characterized by an increase in sympathetic nerve activity (which occurs after ~40 s; Refs. 19, 20). This delayed increase in sympathetic activity with CFS has been shown to reduce blood flow to the periphery and increase mean arterial pressure (5, 9, 19, 20, 45). It was expected, therefore, that prolonged (e.g., 2 min) CFS application through the onset of exercise would induce overall effects not dissimilar to interventions such as {beta}-adrenergic blockade (e.g., Refs. 21, 24-26, 39). The actions of both propranolol and metoprolol limit maximal HR and reduce its steady-state value; however, it has not been consistently shown to slow the kinetics of the HR response [Hughson (24) showed no change in {tau} HR, whereas Petersen et al. (39) showed only a small, 5-s slowing), which may limit O2 delivery. Application of CFS in the study, on the other hand, slowed the {tau} HR by >20% (or ~13 s), providing potential for limiting O2 delivery on transition to heavy exercise.

This substantial reduction in HR, both before and during the first minutes of exercise in the present study, resulted in a significantly increased Td for HR, suggestive of an increased limb-to-lung transit time resulting from a slowed circulation. This circulatory delay was mirrored in the O2 response (significant only when CFS was considered independently of bout number), but had no effect on its {tau} (either effective {tau} or {tau}p). Although we had no measure of peripheral blood flow or O2 transport to the exercising limb during the period of CFS manipulation in this study, we attempted to elucidate the degree to which CFS limited blood flow in the femoral artery before the onset of exercise by using the simultaneous pulsed and echo Doppler method (3.5 MHz, EUB-415, Hitachi Medico; e.g., Ref. 11). Three subjects had confirmatory measurement of leg blood flow in a similar upright position on the cycle erogmeter as used in the exercise studies. Figure 4 summarizes these findings and demonstrates that leg blood flow and HR showed a similar pattern of response before exercise during CFS. In fact, blood flow was reduced by ~80% from the resting baseline on application of CFS and by ~50% before the second exercise bout. Noninvasive measurement of femoral artery blood flow is technically challenging during cycle ergometry because of the movement of the limbs and vessels during the exercise. It remains unclear whether the exercising blood flow was also attenuated by the CFS manipulation in this study; however, these data do suggest that the significantly attenuated central circulation ({tau} HR) may be conducted to the periphery as reflected in the leg blood flow response. Resolution of whether blood flow blunting via CFS is maintained during exercise awaits further study.



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  		Fig. 4. Time-averaged group mean (n = 3) values of heart rate [top; in beats/min (bpm)] and femoral artery blood flow (bottom) responses to CFS application during the 1 min before the onset of first (A) and second (B) exercise bouts. Blood flow to the right leg was obtained by using simultaneous pulsed and echo Doppler ultrasound system with a 3.5-MHz probe (with an angle of insonation of 55-60°) to measure mean blood flow and femoral artery diameter from a site 2 cm distal to the inguinal ligament. CFS manipulation demonstrated that leg blood flow and heart rate showed a similar pattern of response during CFS.

 

In support of this contention, Hayashi et al. (18) showed that increased vagal activity via CFS during moderate-intensity exercise delayed the HR and cardiac output response but did not alter the O2 kinetics (similar to the present findings). Therefore, the results of the present study in the context of reduced preexercise blood flow and the induced peripheral vasoconstriction (5, 9, 19, 20, 45) indicate that the cause(s) of the facilitated O2 kinetics during the second exercise bout may not normally be attributable to an improvement in circulatory dynamics. Although O2 delivery has previously been demonstrated not to be a limiting factor in the moderate domain (sub-LT) of cycling exercise (17) and on the first bout of heavy-intensity exercise (50, 55), such experimental manipulations have not, to our knowledge, been applied to investigate the mechanism of O2 speeding during the second bout of supra-LT cycle ergometry.

Vascular vs. metabolic limitation? The physiological mechanism(s) underlying the "facilitated" O2-kinetics during repeated bouts of identical supra-LT exercise may be linked to the etiology of the complex O2 kinetics manifest in the heavy-intensity exercise domain, mainly reflected in the adaptation of the slow component (i.e., between N1 and N2) (Table 1, Fig. 3). Similar to moderate-intensity exercise, there have been two main lines of thought proposed to determine the O2 response at the onset of supra-LT exercise: 1) the rate of O2 transport to the exercising muscle (vascular limitation) or 2) the ability of the exercising muscle to utilize O2 (metabolic inertia) (14, 25, 27, 34, 48, 53).

Gerbino et al. (13) speculated that a circulatory limitation contributed to the slowed O2 kinetics during supra-LT work intensities after demonstrating an appreciably facilitated O2 response during the second exercise bout after a prior identical supra-LT "conditioning" bout. This hypothesis of a circulatory limitation during heavy-intensity exercise has since been supported by several studies. For example, MacDonald et al. (32) showed that enhanced O2 delivery, by hyperoxic inspiration, accelerated the O2 mean response time during heavy-intensity leg cycling exercise, although, similar to the present study, {tau}p remained unaffected. Also, when heavy knee-extension exercise was performed in the supine compared with the upright position, these authors showed that a slowed femoral artery blood flow was associated with a slowed O2 response (33). Similarly, Grassi et al. (16) were able to elicit a faster adjustment of muscle O2 in canine gastrocnemius by increasing muscle blood flow during "peak" stimulations. Most recently, Tordi et al. (47) demonstrated that, during exercise that elicited ~97% of peak O2, a faster {tau}p was manifest when cardiac output was increased by prior repeated 30-s-"sprint" cycling exercise in humans. However, Behnke et al. (4) have shown in the rat intact-spinotrapezius muscle that the {tau} (similar to {tau}p in the present study) of microvascular PO2 fall was, in fact, similar between repeated stimulation bouts, suggestive of adequate O2 delivery. These authors also found that the Td of bout 2 was reduced, thereby reducing the "effective" {tau} of bout 2, similar to the results herein. Behnke et al. (4) suggested that these results, measuring the balance of O2-to-blood flow, reflected an intramuscular, rather than a blood flow-mediated limitation of mO2 during bout 1, which was manifest with a shorter delay on transition to bout 2.

In humans, impositions to adjust limb O2 delivery before heavy-intensity exercise, such as lower body positive pressure (55) or by a maneuver to induce a reactive hyperemia (50), have similarly failed to alter {tau}p O2 during the first exercise bout. Furthermore, recent studies (31, 38, 49) using handgrip exercise and single or repeated bouts (presumably in the heavy-intensity domain), demonstrated that mO2 and blood flow manifested similar adaptations of response. In other words, improved O2 delivery speeded the mO2 response on-transition to the second bout of handgrip exercise after an identical conditioning bout, such that forearm mO2 during the first 30 s of the second bout of exercise was elevated compared with that in the first bout with a concomitant increase in blood flow to the forearm (31). However, because of the constraints of the experimental mode, the authors could not estimate the kinetic parameters of these changes. Furthermore, despite speeded O2 kinetics at the onset of peak intensity exercise in the isolated canine gastrocnemius (16), a similar effect during exercise that elicited 60-70% of maximal O2 (15) was not found. In addition, Fukuba et al. (10) found no effect of a comparable systemic residual lactic acidosis (generated by exercising a different muscle group, i.e., arm) on subsequent O2 kinetics at the onset of heavy-intensity leg cycling exercise, despite the potential beneficial effects of peripheral vasodilatation and a rightward shift of O2 dissociation curve (i.e., Bohr effect). It seems, therefore, that although the dynamics of cardiac output or blood flow is consistently faster than O2 at the onset of both moderate-intensity (8) and heavy-intensity exercise (e.g., Refs. 17, 33), this may not be the case during severe exercise (16, 47). Nevertheless these observations support the metabolic inertial hypothesis in determining the characteristics of the O2 response at the initial-onset, heavy-intensity exercise. However, an attenuating (not augmenting) manipulation applied at the onset of the second bout in the repeated-bouts protocol is, we believe, crucially important because, if the exercise itself were to reduce or remove an intramuscular "stenosis" that operates during the first exercise bout, it is possible that the elevated blood flow, apparent at the onset of the second bout, could play a role in the facilitation of the O2 response observed during N2. Therefore, our hypothesis, that the O2 response at the onset of the second bout of exercise would be suppressed by the attenuation O2 delivery (i.e., by the CFS manipulation) was not supported by the results of the present study. Despite the delayed circulatory adaptation at exercise onset induced by CFS (Table 2, Figs. 2 and 4), there was no concomitant slowing of O2 response at the onset of the second bout of heavy-intensity exercise (Table 1, Fig. 3).

The mechanism(s) underlying the facilitated O2 response (manifest as either a speeding of the fundamental {tau}p, a reduction in the slow component, or both) at the onset of the second exercise bout during repeated exercise, therefore, remain(s) to be elucidated. Rossiter et al. (44) have suggested that the O2 slow component during the repeated-bouts protocol in humans was related to an intramuscular event linked to phosphocreatine degradation, which was in accord with the demonstration of Poole et al. (41) that ~80-90% of the pulmonary O2 slow component could be accounted for by the associated increase in leg O2. Consequently, the control of the O2 slow component is commonly ascribed to factors related to the exercising limb, rather than to rest of the body. Therefore, we believe, mechanisms proposed to explain the facilitated O2 in the second bout are more likely to be ascribed to an intramuscular event such as the pattern of motor unit recruitment and/or fatigue (1, 43); intracellular factors other than O2 availability (22), which may arise from either activation of the pyruvate dehydrogenase complex (23, 46); a relationship to the attenuation of the blood lactate increase (10, 13), or altered phosphate-mediated feedback control (44).

In summary, therefore, this study demonstrated that O2 dynamics were not altered under conditions of increased vagal activity resulting from CFS manipulation before and after the onset of exercise despite a clearly delayed and slower HR response. Contrary to our hypothesis, the O2 response during the second bout of repeated supra-LT cycling did not revert toward the response of the initial exercise bout, when a reduced circulatory dynamic was imposed via CFS. This suggests that the marked adaptation of O2-kinetics during the second bout of supra-LT exercise may not be manifest by an O2 delivery-related mechanism. Rather, these data implicate mechanisms more proximally related to muscular ATP breakdown in mediating this phenomenon.


   DISCLOSURES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 DISCLOSURES
REFERENCES
 
This study was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (nos. 10680048 and 12680048) and Uehara Memorial Life Science Foundation. H. B. Rossiter is an International Prize Traveling Fellow of the Wellcome Trust (United Kingdom) (no. 064898).


   FOOTNOTES
 

Address for reprint requests and other correspondence: Y. Fukuba, Dept. of Exercise Science and Physiology, School of Health Sciences, Hiroshima Prefectural Women's Univ., 1-1-71, Ujina-higashi, Minamiku, Hiroshima 734-8558, Japan (E-mail: fukuba{at}hirojo-u.ac.jp).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 DISCLOSURES
 REFERENCES
 

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