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ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY
1Département de Physiologie, Centre Médical Universitaire, Genève, Switzerland; 2Département d'Anesthésiologie, Pharmacologie et Soins Intensifs Chirurgicaux, Hôpital Cantonal Universitaire, Bâtiment Opéra, Genève, Switzerland; 3Laboratorio di Fisiologia, Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, Udine, Italy; and 4Sezione di Fisiologia Umana, Dipartimento di Scienze Biomediche e Biotecnologie, Università di Brescia, Brescia, Italy
Submitted 24 May 2005 ; accepted in final form 8 October 2005
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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aO2) at exercise start was faster than that of lung O2 uptake (
O2), being dictated by that of cardiac output (), and whether changes in would explain the postulated rapid phase of the O2 increase. Simultaneous determinations of beat-by-beat (BBB) and aO2, and breath-by-breath O2 at the onset of constant load exercises at 50 and 100 W were obtained on six men (age 24.2 ± 3.2 years, maximal aerobic power 333 ± 61 W). O2 was determined using Grønlund's algorithm. was computed from BBB stroke volume (Qst, from arterial pulse pressure profiles) and heart rate (fH, electrocardiograpy) and calibrated against a steady-state method. This, along with the time course of hemoglobin concentration and arterial O2 saturation (infrared oximetry) allowed computation of BBB aO2. The , aO2 and O2 kinetics were analyzed with single and double exponential models. fH, Qst, , and O2 increased upon exercise onset to reach a new steady state. The kinetics of aO2 had the same time constants as that of . The latter was twofold faster than that of O2. The O2 kinetics were faster than previously reported for muscle phosphocreatine decrease. Within a two-phase model, because of the Fick equation, the amplitude of phase I changes fully explained the phase I of O2 increase. We suggest that in unsteady states, lung O2 is dissociated from muscle O2 consumption. The two components of and aO2 kinetics may reflect vagal withdrawal and sympathetic activation. cardiovascular response
O2), the O2 was investigated to gain information on O2 consumption (15, 16).
This correspondence, however, was questioned. In fact, the kinetics of O2 consumption requires that it be sustained by adequate O2 transfer from ambient air to mitochondria. Thus, concomitant with the increase in O2 consumption, there must be 1) an increase in O2; 2) an increase in O2 flow in arterial blood [or systemic O2 delivery (aO2) that is the product of cardiac output (), times arterial O2 concentration, CaO2], most of which, during exercise, is directed to the contracting muscles; and 3) an increase in the diffusive O2 flow from capillaries to mitochondria. Concerning O2, some authors (56, 57) have proposed that its kinetics imply two components: a rapid "cardiodynamic" phase (phase I), due to potential transitory effects of an immediate cardiac response on O2 during the earliest seconds of exercise, followed by a slower monoexponential increase (phase II), related to the metabolic adaptations in contracting skeletal muscles. This view restricts the correspondence between lung O2 uptake and muscle O2 consumption to the monoexponential phase II. Perhaps the strongest piece of evidence in support of the phase I concept is the finding that the kinetics of cardiac output () upon light exercise onset is much faster than that of O2 (12, 14, 21, 34, 38, 59, 60). In fact, assuming invariant O2 concentration in mixed venous blood in the first seconds of exercise, this finding would imply, according to the Fick principle, a corresponding rapid increase in O2.
As far as aO2 is concerned, it can clearly be hypothesized that its kinetics during light exercise may, in fact, be faster than that of O2. If we assume that CaO2 remains unchanged also in the exercise transient, as normoxic subjects operate about the flat portion of the O2 dissociation curve, then the kinetics of aO2 would have to be similar to that of . Therefore, because of the rapid kinetics, the aO2 kinetics is expected to be much faster than that of O2. To the best of our knowledge, however, the kinetics of aO2 on exercise onset has yet to be determined in humans. The kinetics of femoral artery O2 flow was determined during single-leg exercise and found to be only slightly faster than that of leg O2 during single-leg exercise in humans (27), in contrast with what may be expected at the systemic level.
In this study, we aimed to make simultaneous determinations of aO2 and on a beat-by-beat basis, for the first time, in conjunction with breath-by-breath O2 in the same human subjects. We, therefore, tested at the whole body level whether at the onset of light aerobic exercise 1) the kinetics of aO2 were, indeed, faster than that of O2 and 2) the kinetics of aO2 had, indeed, the same time constants as that of . Furthermore, because the two-component model of O2 kinetics (56, 57) requires a close quantitative correspondence between and O2 in the first phase of the transient, this experiment allowed us to also test whether or not the changes in amplitude of the explained entirely the corresponding O2 increase in the first phase.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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Measurements.
O2 was determined at the mouth on a breath-by-breath basis. The time course of O2 and CO2 partial pressures throughout the respiratory cycles were continuously monitored by a mass spectrometer (Balzers Prisma, Balzers, Liechtenstein) and calibrated against gas mixtures of known composition. The inspiratory and expiratory ventilations were measured by an ultrasonic flowmeter (Spiroson, Ecomedics, Duernten, Switzerland) calibrated with a 3-liter syringe. The alignment of the traces was corrected for the time delay between the flowmeter and the mass spectrometer. Breath-by-breath O2 and CO2 output (CO2) were then computed by means of the Grønlund's algorithm (8). A software specifically written under the Labview developing environment was used.
Heart rate (fH) and arterial O2 saturation (SaO2) were continuously measured by electrocardiography (Elmed ETM 2000; Augsburg, Germany) and by fingertip infrared oximetry (Ohmeda 2350; Finapres, Madison, WI), respectively. Continuous recordings of arterial pulse pressure were obtained at a fingertip of the right arm by means of a noninvasive cuff pressure recorder (Portapres, TNO, Eindhoven, The Netherlands). Beat-by-beat mean arterial pressure () was computed as the integral mean of each pressure profile, using the Beatscope software package (TNO).
The stroke volume of the heart (Qst) was determined on a beat-by-beat basis by means of the model flow method (55), applied off-line to the pulse pressure profiles, using again the Beatscope software package. Beat-by-beat was computed as the product of single beat Qst times the corresponding single beat fH. Each beat-by-beat value was then corrected for a proportionality factor to account for the method's inaccuracy (2). To this end, steady-state values were obtained also by means of the open-circuit acetylene method (3). In practice, at rest and at minute 7 of each exercise period, the subject inhaled a normoxic gas mixture containing 1% acetylene and 5% helium for at least 20 respiratory cycles. During this measurement, inspired air was administered from precision high-pressure gas cylinders via an 80-liter Douglas bag buffer. The gas flow from the cylinders was adjusted to the subject's ventilation. For each subject, the partition coefficient for acetylene was determined on a different occasion by mass spectrometry (36), on 5-ml venous blood samples. Individual correction factors at rest and at each workload were calculated by dividing the values obtained with the open-circuit acetylene technique by the corresponding average values obtained with the model flow method. ANOVA showed no effect of exercise on the correction factor (P > 0.05) but significant differences among subjects (P < 0.05). Thus individual mean correction factors were used, on the assumption of no significant changes of them during the exercise transients. Correction factors ranged between 0.98 and 1.47 (mean 1.264 ± 0.187).
Exercise was carried out on an electrically braked cycle ergometer (Ergometrics 800-S; Ergoline, Bitz, Germany). The pedaling frequency was recorded, and its sudden increase at the exercise onset and decrease at the exercise offset were used as markers to identify precisely the start and the end of exercise. The electromechanical characteristics of the ergometer were such as to permit workload application in <50 ms.
All of the signals were digitized in parallel by a 16-channel A/D converter (model MP 100; Biopac Systems, Santa Barbara, CA) and stored on a computer. The acquisition rate was 100 Hz.
Blood hemoglobin concentration, [Hb], was measured by a photometric technique (HemoCue, Angelholm, Sweden) on 10-µl blood samples from a peripheral venous line inserted into the left forearm. Blood lactate concentration, [La]b, was measured by an electroenzymatic method (Eppendorf EBIO 6666, Hamburg, Germany) on 20-µl blood samples from the same venous line. Arterial blood gas composition was measured by microelectrodes (Synthesis 10; Instrumentation Laboratory, Milano, Italy) on 300-µl blood samples taken from an arterial catheter inserted in the left radial artery.
Protocol. After performance of blood sampling and measurement of acetylene cardiac output at rest, 2 min of quiet rest was allowed. Then, the exercise at 50 W started, lasting for 10 min. Arterial blood gas composition and [La]b were measured at minute 5 and at the end of exercise. At minute 7, the acetylene cardiac output was measured. The 50-W exercise was followed by a 10-min recovery period, during which [La]b was measured at minutes 2, 4, and 6, and arterial blood gas composition was determined at minutes 5 and 10. Then, the 100-W exercise was carried out, for a 10-min duration, and with the same timing of events as at 50 W. A 10-min recovery followed, with the same characteristics as for the previous one. The overall duration of this protocol was about 50 min, during which [Hb] was systematically measured at 1-min intervals.
Each subject repeated this protocol four times. At each repetition, the performance of blood sampling for [Hb] determination was shifted by 15 s without changing the 1-min interval between successive measurements, so that, for repetitions 1, 2, 3, and 4, respectively, the first [Hb] determination took place at overall protocol time 0, 15, 30, and 45 s, the second at overall protocol time 60, 75, 90, and 105 s, and so on until the end of an experimental session. When the four tests were superimposed, this time shift allowed an overall description of the changes in [Hb] on a 15-s time basis.
Data treatment. The superimposed time course of [Hb] was smoothed by a four-sample mobile mean, to account for interrepetition variability, and interpolated by means of a 6th degree polynomial. SaO2 was averaged among the four repetitions and interpolated by means of a 6th degree polynomial. The resulting functions, describing the time course of [Hb] and SaO2, were used to compute the time course of arterial O2 concentration (CaO2, ml/l), on an equivalent beat-by-beat time scale, established after the pulse pressure profile traces, as
 | (1) |
where constant 
(1.34 ml/g) is the physiological O2 binding coefficient of hemoglobin, and time (t) corresponds to the time of each heart beat.
The beat-by-beat fH, Qst, 
, and values from the four repetitions were aligned temporally, by setting the time of exercise start or stop as time 0 for the analysis of on- and off-kinetics, respectively. Then they were averaged on a beat-by-beat basis to obtain a single averaged superimposed time series for each parameter. Beat-by-beat aO2 was then calculated as
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Beat-by-beat total peripheral resistance (RP) was calculated by dividing each value of by the corresponding value, on the assumption that the pressure in the right atrium can be neglected as a determinant of peripheral resistance.
The breath-by-breath O2 values were interpolated to 1-s intervals (30). Then the four repetitions were aligned temporally, as described above, and averaged to obtain a single averaged superimposed time series also for O2.
Models.
Several authors have proposed that the kinetics of O2 during light or moderate exercise, hindered by the inertia of the metabolic activation at the onset of muscle contraction, is conveniently described by a single capacitance model (5, 19). Within this context, and thus assuming that O2 reflects closely muscle O2 consumption, so that it is legitimate to infer from the former on the latter, the O2, , and aO2 kinetics at the onset of exercise would be described by the following monoexponential equations, respectively
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 | (3b) |
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where suffix ss indicates the average steady state value (net value above resting), and k is the velocity constant for the parameter at stake—note that k is the reciprocal of the time constant 
.
Some authors have proposed an alternative to the single capacitance model; it is a more complex model (4, 56), defined here as the two-phase model, whereby an exponential increase in flow (phase II), related to metabolic adaptation in skeletal muscle, is preceded by a faster flow increase in the first seconds of exercise (phase I), which Barstow and Molé (4) treated as an exponential. In the context of this model, the net O2 kinetics upon exercise onset is described by
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where k1 and k2 are the velocity constants of the exponential parameter (O2 in this case) increase in phase I and II, respectively, d is the time delay, and A1 and A2 are the amplitude of the parameter increase during phase I and phase II, respectively. H(t – d) is the Heaviside function defined as
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In the context of the same model, by analogy, the kinetics of and aO2 at the onset of exercise are described by
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 | (4c) |
Statistics. At the steady state, data are given as means ± SD. The effects of exercise intensity on the investigated parameters was analyzed by one-way ANOVA. A post hoc Bonferroni test was used to determine differences between pairs. Normal distribution of errors was assumed. The results were considered significant if P < 0.05.
During transients, the characteristic parameters of the two analyzed models were estimated by means of a weighted nonlinear least squares procedure (9), implemented in the commercial software Labview 5.0 (National Instruments, Austin, TX). Initial guesses of the parameters of the model were entered after visual inspection of the data. The characteristic parameters are given as means ± SD. A nonparametric Wilcoxon test for paired observations was used 1) to evaluate the effects of exercise on the time constants of O2, , and aO2 and 2) to perform a comparison of the time constants of O2, , and aO2 at each of the investigated workloads. The results were considered significant if P < 0.05.
Intersubject variability and effects of exercise intensity on the correction factor for beat-by-beat determination of were evaluated with the Kruskal-Wallis test (13).
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RESULTS |
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, upon the onset of 50 W and 100 W exercises are shown in Figs. 1 and 2, respectively. All of these parameters increased upon exercise onset to reach a new steady state. The time course of and Rp upon the onset of 50 W and 100 W exercise are jointly reported in Fig. 3. At exercise start, there was a sudden decrease in , followed by a rapid increase, this within the first 20 s of exercise: at 100 W, this increase was such as to lead to a overshoot. Afterward, increased progressively, to attain a steady-state value higher than resting. Rp decreased very rapidly at exercise start, to reach a new steady-state value lower than at rest.
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, is shown in Fig. 4. The resting values are located on the lower-left side of the plot; the exercise steady-state values are located on the upper-right side. The pattern of displacement of the fH vs operational site from rest to exercise is characterized by a rapid increase in fH correcting the sudden fall at exercise start. This is translated into a shift leftward and upward of the relationship between fH and that precedes the rightward shift toward the new baroreflex operational site.
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aO2 and O2 upon the onset of 50 W and 100 W exercises are jointly reported in Fig. 6. To facilitate a comparison of the two parameters, data has been expressed in relative terms, whereby resting values were set equal to 0 and steady-state values were set equal to 100%. Both aO2 and O2 increased upon exercise onset to reach a new steady state and decreased upon exercise offset to return to the respective resting values. However, the rate of readjustment of aO2 at exercise onset appeared to be faster than that of O2.
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, fH, Qst, aO2, O2, , and Rp, are reported in Table 2. Mean , fH, Qst, aO2 and O2 were higher at 50 W exercise than at rest, and at 100 W exercise than at 50 W. was higher at exercise than at rest. However, because its increase was smaller than that in , Rp resulted lower at exercise than at rest.
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, aO2, and O2 kinetics at exercise onset are presented in Tables 3 and 4, for the single capacitance and the two-phase models, respectively. With both models the time constants for and aO2 were not significantly different between them and resulted twice as fast as those for O2 (P < 0.05).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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aO2 and on a beat-by-beat basis, for the first time, in conjunction with breath-by-breath O2 in the same human subjects. The main findings were that 1) the kinetics of was twice as fast as that of O2, no matter what model was applied; 2) the kinetics of aO2 had the same time constants as that of , no matter what model was applied, because CaO2 oscillations were so slow that CaO2 remained essentially unchanged during the first minute of exercise, in agreement with previous reports (27); and 3) using a two-phase model, the amplitude of phase I changes could fully explain the ensuing amplitude of phase I O2 increase. The first of these findings is consistent with and provides quantitative support to previous observations of a fast increase in upon exercise onset (12, 14, 21, 38, 59, 60). The second finding demonstrates that the kinetics of aO2 is indeed dictated by that of , thus being by far faster than that of O2. So this finding does not support the assumptions of the single capacitance model for O2 kinetics on exercise onset and suggests a potential dissociation between O2 and muscle O2 consumption in unsteady states. The third finding provides full quantitative support to the notion of a -dependent phase I of the O2 kinetics.
Methodological considerations.
The highest workload imposed to the subjects was <40% of their maximal aerobic power. There was no significant increase in [La]b during exercise, whereas pH and PaCO2 values were not significantly different from resting (Table 1). As a consequence, all exercise was carried out below the so-called anaerobic threshold, and early lactate accumulation during the exercise transients (11) and the appearance of a third phase of the O2 kinetics characterized by a continuous increase in O2 and fH (7, 58) were avoided.
Breath-by-breath O2 was computed by the Grønlund algorithm (8). Indeed, classical algorithms for single-breath determination of alveolar gas exchange, all based on the concepts originally introduced by Auchincloss et al. (1), require the assumption of a fixed value for the end-expiratory alveolar volume. This assumption was demonstrated to increase the variability of breath-by-breath O2 assessment (18). Grønlund circumvented this problem by making the O2 computation algorithm independent of the end-expiratory alveolar volume (28). Grønlund's algorithm was validated at rest and at the exercise steady state against the standard open circuit method and against numerous algorithms derived from Auchincloss; it was demonstrated to provide the same steady-state values, yet with much less variability around the mean value than for any other tested algorithm (8). Furthermore, a comparative analysis of algorithms derived from Auchincloss during exercise transients demonstrated a linear relationship between end-expiratory lung volume and phase II time constant of O2– kinetics, allowing the conclusion that these algorithms generate spurious O2 kinetics at the onset of exercise, whereas the time constants provided by Grønlund's algorithm were systematically faster than with any other algorithm (10). Thus Grønlund's algorithm increases the precision of single-breath O2 assessment and allows more accurate estimates of the O2 kinetics during step exercise transients.
was measured by application of the model flow method to pulse pressure profiles obtained noninvasively from a fingertip artery. The method assumes impedance characteristics of the arterial wall of the aorta (31), whereas fingertip pressure profiles are typical of peripheral arteries. This discrepancy causes lower absolute pressure values and inaccurate values (2, 25). To use this method for obtaining beat-by-beat values, a correction for an established steady-state method simultaneously applied on the same subjects must be carried out. This justifies the simultaneous performance of measurements by the open circuit acetylene technique in this study and the application of a correction procedure, as previously described (49). Calculated correction factors did not differ significantly among both workloads and subjects. This allowed application of an overall correction factor of 1.264, which turned out to be similar to that previously reported with the same techniques (49). After correction, model flow computation can be conveniently applied also during dynamic states with rapid changes in (51).
[Hb] cannot be measured continuously or on a beat-by-beat basis, as required by the computation of beat-by-beat aO2. We had [Hb] determinations at 1-min intervals, and the 15-s shift in blood sampling from one repetition to the other allowed to obtain, across repetitions, [Hb] values at 15-s intervals. These values, however, are affected by the intrinsic variability of [Hb] from one day to the other, which was dealt with by applying a mobile mean smoothing technique over four [Hb] values. Interpolation allowed the construction of a function, whereby the time course of [Hb] was estimated. In so doing, estimated [Hb], and thus CaO2, values at the time of each heart beat could be attributed to the corresponding beat-by-beat values, to compute beat-by-beat aO2.
Cardiovascular adjustments during the exercise transient.
The rapid increase in (Fig. 2) is the result of a number of regulatory mechanisms that are activated at exercise onset. As exercise starts, a strong and prompt decrease in Rp takes place (Fig. 3), with subsequent dramatic and fast increase in muscle or limb blood flow (23, 27, 44, 50, 52). Whatever the causes of the Rp fall—vasodilatation (myogenic, neurogenic, see Ref. 32) and/or muscle pump action (48), its immediate effect is the sudden, transient drop in (Fig. 3). This fall cannot be corrected for by an increase in fH induced by arterial baroreflexes, because mean values of are at the margins, if not outside, the operational baroreflex range. Correction of requires more drastic responses. These would include an immediate resetting of baroreflexes (Fig. 4), as demonstrated at the exercise steady state (29, 39, 41, 43). Such a resetting may be driven either by the changes in Rp (40) or by afferent inputs from skeletal muscle receptors (42) or eventually anticipated by a kind of "central command" mechanism (24). Moreover, a withdrawal of the vagal drive to the heart occurs (22), which would explain the sudden step increase in fH (Fig. 1). Finally, muscle and/or diaphragmatic pump action may lead to a sudden increase in venous return, with consequent corresponding increase in Qst (data not shown in Figures) due to the Frank-Starling mechanism, as demonstrated in dogs (47).
Baroreflex resetting and withdrawal of vagal drive may, in fact, explain a great deal of the cardiovascular response at the onset of exercise (20) and design an overall on/off switch of the global regulation of the cardiovascular system, and perhaps also of the respiratory system, upon exercise onset. However, the resulting increase in would not be possible without a concomitant immediate increase in venous return due to muscle pump action.
If this is so, the kinetics of upon exercise onset would be better represented by a two-phase rather than a single capacitance model. The first, immediate, phase would account for baroreflex resetting, withdrawal of vagal drive, and increase in preload; the second, delayed and kinetically slower, phase might parallel sympathetic drive stimulation.
Of the O2 and aO2 on kinetics.
Application of the single capacitance model to the description of O2 kinetics relied on the assumption that, once possible changes in blood O2 stored are accounted for, lung O2 reflects muscle O2 consumption. This assumption implies that the time constant of O2 ought to be equal to that of muscle O2 consumption, or of its mirror image, the muscle phosphocreatine decrease. This seemed to be the case in previous studies (15, 33), in which algorithms based on Auchincloss's principles were used (1). Furthermore, a correspondence between the time constant of O2 and that of muscle phosphocreatine decrease was reported in a study on single-leg extension exercise (45), further reinforcing this notion. In the present study, however, faster time constants for O2 were obtained than in previous studies (15, 33) with the same exercise mode and intensities. The present time constants for O2 were also faster than those found by others for the monoexponential phosphocreatine decrease upon exercise onset (6, 17, 45), a mirror image of muscle O2 consumption independent of the exercise mode. These fast time constants, perhaps an intrinsic consequence of the improved computational method (10), suggest a lack of correspondence between lung O2 and muscle O2 consumption.
On the other hand, the time constants of and aO2 were definitely faster than those of O2. These findings reinforce the concept that the kinetics of aO2 and of O2 are dissociated. If this is so, then changes in O2 extraction should occur and an "early" effect of aO2 on O2 should be seen, as originally postulated by Wasserman et al. (53) and modeled by Barstow and Molé (4). In fact, these authors assumed similar time constants for pulmonary blood flow as found in the present study for and aO2. Extension of the single capacitance model to the description of the kinetics of and aO2 requires the assumption of a close matching of O2 to aO2. This assumption is not supported by the present results.
The kinetics of leg O2 and leg O2 flow during single-leg exercise were also analyzed by means of a single capacitance model (27). The time constant of leg O2 flow was found to be only slightly faster than that of the leg O2, despite the well-known rapidity of muscle blood flow adaptation at exercise onset (23, 27, 44, 50, 52). Yet the present time constants for and aO2 were definitely faster than those reported for leg O2 flow, suggesting that muscle O2 transfer and systemic O2 flow are the consequence of different, independent phenomena. More recently, on isolated, perfused dog gastrocnemii, the time constant of the O2 kinetics was found to be equal in conditions of normal and forced O2 delivery and equal to that calculated for the kinetics of muscle phosphocreatine decrease (26), demonstrating an independent peripheral component of the kinetics of muscle O2 consumption.
The results obtained with the two-phase model provided a phase I time constant of O2 kinetics that was extremely rapid and functionally instantaneous. This would correspond to a practically immediate upward translation of O2 visible since the first breath. Very fast time constants of phase I (Table 4) were found also for the kinetics of and aO2, compatible with the notion of immediate vagal withdrawal. These time constants cannot be considered different from those obtained for O2 as far as the minimal time window on which the O2 kinetics can be determined is one breath length. The results of the present analysis refine and support quantitatively the observation (12) of a close correspondence between the rapid increase of and ventilation at exercise onset. For all parameters, the time constants of phase II were slower than those of phase I at 100 W, but at 50 W, they were as fast as those of phase I. At both workloads, phase II time constants of and aO2, which may reflect slower sympathetic activation, remained by far faster than those of O2, but the time delay was the same. Thus the phase II of the aO2 kinetics would only partially explain the phase II of the O2 kinetics. Finally, the phase II time constants were slightly but significantly faster than those found within the single capacitance model, as a consequence of the introduction of a time delay. Nevertheless, the time constant of O2 in phase II resulted in faster time constants than reported (4, 57) in studies in which algorithms derived from Auchincloss et al (1) were used and remained faster than previously reported for muscle phosphocreatine decrease (6, 17, 45), suggesting again possible dissociation between lung O2 uptake and muscle O2 consumption.
In two cases at 50 W, phase II could not even be identified by the fitting procedure, and the overall kinetics of was accounted for by a single component. Within the context of a two-phase model, this might have been the consequence of an initial overshoot that perhaps concealed the second phase increase in . Nevertheless, the question arises as to whether sympathetic activation really occurs during very low workloads, and thus as to whether a single capacitance model, with a very fast time constant, would provide a complete description of the events occurring in the cardiovascular system upon light exercise onset.
aO2 is the product of times CaO2. CaO2 variations paralleled those of [Hb] (Fig. 5) and were subject to slow oscillations, with a period ranging between 4 and 5 min. Within the time window of the exercise transients, even in the case of greatest oscillation amplitude (20 ml/l), the effects of these oscillations on CaO2 were at most 1% and thus introduced a practically negligible distortion of the aO2 kinetics with respect to that of . In fact, the time constants of the two phases of the aO2 kinetics did not result significantly different from those of . This allows the conclusion that the kinetics of aO2 upon exercise onset is, indeed, dictated by that of .
If we look at the Fick principle, it helps us understand whether the phase I of the or aO2 kinetics explains the phase I of the O2 kinetics at the mouth. Because of a delay between muscle O2 consumption and lung O2 uptake, we can reasonably assume that during the first seconds of exercise, the composition of mixed venous blood remains unchanged, and thus arterial-venous O2 difference (CaO2-CvO2) stays equal to that at rest (4, 54). This being so, any increase in O2 during phase I would be a consequence of an increase in only. The amplitude of phase I was on average 4.3 l/min (see Table 4). This amplitude, for an average resting CaO2-CvO2 of 87 ml/l, would produce a corresponding immediate O2 increase of 374 ml/min, which is very close to the observed amplitude of phase I for O2, reported in Table 4 (355 ± 148 ml/min). This computation allows the conclusion that the amplitude of phase I for O2 is indeed entirely accounted for by the increase during phase I, in agreement with the hypothesis put forward by others (56, 57). This analysis further supports the notion of a possible dissociation between lung O2 and muscle O2 consumption.
In conclusion, the kinetics of and aO2 upon exercise onset were significantly faster than that of lung O2, as expected. Consistent with the Fick principle, this finding implies a rapid component in the O2 kinetics. Application of a two-phase model showed that the amplitude of phase I O2 increase is entirely accounted for by the amplitude of phase I O2 increase. The second phase of the O2 kinetics is only partially related to the second phase of and aO2 kinetics. The kinetics of aO2 is entirely dictated by the kinetics of . The fast time constants of O2, as well as the fast time constants of aO2 in relation to O2, suggest the potential dissociation between O2 and muscle O2 consumption in unsteady states. We speculate that O2 kinetics is under the influence of the systemic cardiovascular response to exercise, whereas only muscle O2 consumption kinetics is affected by the metabolic regulatory processes. This being the case, the two components of the cardiovascular response to exercise (phase I and phase II) may reflect vagal withdrawal and sympathetic activation, respectively.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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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.
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O2-on kinetics in isolated in situ canine muscle. J Appl Physiol 85: 1394–1403, 1998.
