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J Appl Physiol 105: 575-580, 2008. First published May 15, 2008; doi:10.1152/japplphysiol.01129.2007
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Progressive recruitment of muscle fibers is not necessary for the slow component of VO2 kinetics

Jerzy A. Zoladz,1 L. Bruce Gladden,2 Michael C. Hogan,3 Zenon Nieckarz,4 and Bruno Grassi5,6

1Department of Physiology and Biochemistry, University School of Physical Education, Krakow, Poland; 2Department of Kinesiology, Auburn University, Auburn, Alabama; 3Department of Medicine, University of California San Diego, La Jolla, California; 4Department of Physics, Jagiellonian University, Krakow, Poland; 5Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Udine, Italy; and 6Institute of Bioimaging and Molecular Physiology, Consiglio Nationale delle Ricerche, Milano, Italy


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
The "slow component" of O2 uptake (VO2) kinetics during constant-load heavy-intensity exercise is traditionally thought to derive from a progressive recruitment of muscle fibers. In this study, which represents a reanalysis of data taken from a previous study by our group (Grassi B, Hogan MC, Greenhaff PL, Hamann JJ, Kelley KM, Aschenbach WG, Constantin-Teodosiu D, Gladden LB. J Physiol 538: 195–207, 2002) we evaluated the presence of a slow component-like response in the isolated dog gastrocnemius in situ (n = 6) during 4 min of contractions at ~60–70% of peak VO2. In this preparation all muscle fibers are maximally activated by electrical stimulation from the beginning of the contraction period, and no progressive recruitment of fibers is possible. Muscle VO2 was calculated as blood flow multiplied by arteriovenous O2 content difference. The muscle fatigued (force decreased by ~20–25%) during contractions. Kinetics of adjustment were evaluated for 1) VO2, uncorrected for force development; 2) VO2 normalized for peak force; 3) VO2 normalized for force-time integral. A slow component-like response, described in only one muscle out of six when uncorrected VO2 was considered, was observed in all muscles when VO2/peak force and VO2/force-time were considered. The amplitude of the slow component-like response, expressed as a fraction of the total response, was higher for VO2/peak force (0.18 ± 0.06, means ± SE) and for VO2/force-time (0.22 ± 0.05) compared with uncorrected VO2 (0.04 ± 0.04). A progressive recruitment of muscle fibers may not be necessary for the development of the slow component of VO2 kinetics, which may be caused by the metabolic factors that induce muscle fatigue and, as a consequence, reduce the efficiency of muscle contractions.

skeletal muscle bioenergetics

DURING VOLUNTARY constant-load exercise in humans a steady-state of O2 uptake (VO2) is attainable only for moderate-intensity exercise (for review, see Ref. 38), carried out below the so-called lactate threshold (LT). Above LT, after a rapid monoexponential increase ("fundamental," or phase II component of the kinetics), there is a further increase in VO2 (phase III, or "slow" component; 7, 17, 23, 38) that, during very heavy exercise [above "critical power" (38)], may approach maximal O2 uptake (VO2 max), with exhaustion ensuing at or soon after VO2 max is reached (24). The slow component of VO2 kinetics is not exclusive to dynamic exercise. Vøllestad et al. (36), for example, described a slow component of leg VO2 kinetics in humans during repeated isometric contractions of the quadriceps muscle. While the factors responsible for the slow component of VO2 kinetics are still debated (7, 17, 38, 40), it has been demonstrated that the "excess" VO2 associated with the slow component mainly derives from the exercising muscles (25). Traditionally, the slow component of VO2 kinetics is thought to be caused at least partly by a progressive recruitment, as a function of time, of aerobically less-efficient type II fibers (17) as heavy exercise proceeds and the initially recruited fibers become fatigued (5, 7, 17, 38, 40). According to some evidence, mainly obtained from animal studies, oxidative metabolism in type II fibers is characterized by a lower efficiency compared with type I fibers (4), which would explain the "excess VO2," with respect to the constant external power output, associated with the VO2 slow component.

In previous studies (10, 12) on the isolated dog gastrocnemius muscle preparation in situ (33) we occasionally reported a slow component of VO2 kinetics during electrically induced contractions corresponding to submaximal metabolic requirements. Considering that, in our model, all muscle fibers are maximally activated by electrical stimulation from the very beginning of the contraction period, this was a rather surprising observation, apparently in contradiction with the traditional concept of the slow component mentioned above. In our studies (10, 12), however, we did not attempt to interpret the occasionally observed slow component. Moreover, we neglected the fact that the adopted contraction paradigm was not a constant-load protocol, because the muscle fatigued during the contraction period and the developed force significantly decreased as a function of time. The association between a falling force output and a constant VO2 would indicate a reduced efficiency of oxidative metabolism, a process similar to that thought to be responsible for the slow component of VO2 kinetics during constant-load exercise in humans.

In the present study, which represents a reanalysis of data taken from one of our previous papers (10), we hypothesized that after normalizing the VO2 values per unit of force produced, the observed VO2 kinetics would be different from those originally reported. More specifically, a slow component-like response of VO2 kinetics would appear consistently, in the presence of a maximal activation of all muscle fibers from the beginning of the contraction period. The results would allow insights into the issue of whether a progressive recruitment of type II fibers is required for the development of a reduced efficiency of muscle contraction associated with the slow component of VO2 kinetics.


   METHODS
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 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
The original study was conducted with approval of the Institutional Animal Care and Use Committee of Auburn University, Auburn, Alabama, where the experiments were performed. The methods were previously described in detail in the original publication (10) on which the present study is based. What follows is a general description of the experimental protocol, measurements, and data analysis. The present analysis deals only with the "Control" condition (i.e., the conditions in which no drugs were used) of the study, conducted on six adult mongrel dogs.

The gastrocnemius-plantaris-flexor digitorum superficialis muscle complex (for convenience referred to as "gastrocnemius") preparation (33) was used (left leg). Arterial and venous circulations to and from the muscle were surgically isolated. Blood flow (Q) was measured by an ultrasound flow probe (6NRB440, Transonic Systems) positioned in the popliteal vein draining the muscle. The arterial circulation to the gastrocnemius was isolated by ligating all vessels from the femoral and popliteal artery that did not enter the gastrocnemius. The sciatic nerve was exposed and isolated near the gastrocnemius. To evoke muscle contractions, the nerve was stimulated by supramaximal square pulses of 4.0–6.0 V amplitude and 0.2-ms duration (Grass S48 stimulator). Isometric tetanic contractions were triggered by stimulation with trains of stimuli (4–6 V, 200-ms duration, 50-Hz frequency) at a rate of 2 contractions/3 s. On the basis of studies of peak VO2 in this model (1, 19), this stimulation pattern should elicit ~60–70% of peak VO2. The investigated metabolic transition was therefore a rest-to-submaximal (4 min) transition. Force was measured by an isometric myograph. For each contraction, peak force and the integral of the force vs. time tracing were determined (see Fig. 1). At the end of the experiments the dogs were killed with an overdose of pentobarbital sodium and injection of saturated KCl.


Figure 1
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  		Fig. 1. For each contraction, peak force (F peak, see the arrow drawn for the first contraction) and force-time integral (see the shaded area for the second contraction) were calculated. See METHODS for further details.

 
Muscle biopsies were obtained by superficial excision of muscle pieces with a scalpel, at rest and during the last 15 s of the contraction period. Biopsy samples were immediately frozen in liquid nitrogen. Adenosine triphosphate (ATP), phosphocreatine (PCr), and lactate concentrations were determined according to Harris et al. (14). Muscle hydrogen ion concentration was estimated according to Sahlin et al. (30). Free adenosine diphosphate (ADPfree) concentration was calculated according to Kemp et al. (20).

Samples of arterial blood entering the muscle and of venous blood from the popliteal vein were drawn anaerobically. Arterial samples were taken at rest, before the contractions and immediately after the contraction periods. A polyethylene tube was threaded into the popliteal vein cannula to the point where the vein exited the gastrocnemius. This allowed collection of venous blood immediately draining from the muscle. Venous samples were taken at rest (~10 s before the onset of contractions), every 5–7 s during the first 75 s of contractions, and every 30–45 s thereafter until the end of the contraction period. Blood samples were immediately stored in ice and analyzed at 37°C for PO2, PCO2, and pH by a blood gas, pH analyzer (IL 1304, Instrumentation Laboratories), and for hemoglobin concentration ([Hb]) and percent saturation of Hb (SO2, %) with a CO-oximeter (IL 282, Instrumentation Laboratories) set for dog blood.

VO2 of the gastrocnemius was calculated by the Fick principle as VO2 = Q·C(a-v)O2, where C(a-v)O2 is the difference in O2 concentration between arterial blood and venous blood. VO2 was calculated at discrete time intervals corresponding to the timing of the blood samples. Whereas in the original study only uncorrected VO2 (ml·100 g–1·min–1) was considered, in the present study VO2 data were also normalized per unit of peak force, that is per N/100 g (thus, they were expressed as ml O2·min–1·N–1) as well as per unit of force-time integral, that is per N·100 g–1·s, yielding ml O2·min–1·(N·s)–1. Peak force and the force-time integral were measured/calculated at the times corresponding to the blood samplings. Both variables were used for the normalization, since muscle fatigue is usually associated with both a decrease in peak force and with a slower relaxation phase. Thus the force-time integral might better represent the energy demand of force development by the muscle. Data were subsequently fitted by two equations, i.e., by equation 1 and by equation 2. Equation 1 was of the type:

Formula 1(1)
In this equation, yBAS indicates the baseline value obtained at rest before contraction onset, Af indicates the amplitude between yBAS and the steady-state value at the end of the contraction period, TDf the time delay and {tau}f the time constant of the function. The suffix f indicates that these parameters relate to the "fundamental" component of the Formula 1O2 kinetics (38).

Equation 2 was of the type:

Formula 2(2)
In this equation, As, TDs, and {tau}s indicate, respectively, the amplitude, the time delay, and the time constant of the slow component-like response of the kinetics (38). The equation that best fitted the experimental data was determined by F test (see below). That is to say, when equation 2 provided a better fit of the data, a slow component-like response of the Formula 2O2 kinetics was present, superimposed on the fundamental component. The slow component-like response, however, did not always follow an exponential function, being sometimes linearly related to the time of exercise; moreover, its {tau}s values appear devoid of physiological significance. The actual amplitude of the slow component-like response (A's) was estimated as the difference between the last Formula 2O2 value obtained during the contraction period and the asymptotic value of the primary component. The relative contribution of the slow component-like response to the total amplitude of the response was also calculated (13, 29).

Statistical analysis.   Values were expressed as means ± SE. To determine the statistical significance of differences between two means, a paired Student's t-test (2-tailed) was performed. To determine the statistical significance of differences among more than two means, a repeated-measures analysis of variance was performed. A Tukey's post hoc test was used to discriminate where significant differences occurred. Data fitting by exponential functions was performed by an iterative least-squares approach. Comparison between fittings with different exponential models was done via F test. The level of significance was set at P < 0.05. Data fitting and statistical analyses were carried out by using a commercially available software package (GraphPad Prism 4, GraphPad Software).


   RESULTS
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 METHODS
 RESULTS
DISCUSSION
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Mean (±SE) values of peak force and of the force-time integral are given in Fig. 2, top and middle. Figure 2, bottom, shows mean values of the two variables expressed as a percentage of the values determined during the first contraction. For both variables, after a slight increase during the first four to five contractions, possibly attributable to a "staircase" effect, a progressive decrease was observed, indicating fatigue of the contracting muscles. Although at the end of the contraction period the decreases of the two variables were very similar (75.2 ± 4.1% of initial values for peak force vs. 76.5 ± 3.5% for the force-time integral, no significant difference), their time courses were slightly different (see Fig. 2, bottom). Thus Formula 2O2 values were "normalized" to both variables for comparison.


Figure 2
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  		Fig. 2. Mean (±SE) (dashed lines) values of peak force and of force-time are given at top and middle. At bottom, mean values of the 2 variables are expressed as a percentage of the values determined during the first contraction. See RESULTS for further details.

 
Formula 2O2 kinetics analysis.   Individual values of uncorrected Formula 2O2 (Fig. 3, left), Formula 2O2/peak force (Fig. 3, middle), and Formula 2O2/force time integral (Fig. 3, right) are shown in Fig. 3 as a function of the time of contractions. When uncorrected Formula 2O2 was considered, equation 2 provided a better fit for the data (that is, a slow component-like response of Formula 2O2 kinetics was identified) in only one of the six experiments. On the other hand, a slow component-like response was identified in five of six experiments for Formula 2O2/peak force, and in all six experiments for Formula 2O2/force-time integral. The absence of a slow component-like response when uncorrected Formula 2O2 was considered, and the presence of a substantial slow component-like response when Formula 2O2/peak force and Formula 2O2/force-time integral were presented, is also shown in Fig. 4, in which mean (±SE) data are shown.


Figure 3
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  		Fig. 3. Individual values of uncorrected Formula 2O2 (left), Formula 2O2/peak force (middle), and Formula 2O2/force-time integral (right) as a function of the time of contractions. The dashed lines indicate the asymptote of the fundamental component of the kinetics. See Formula 2O2 kinetics analysis for further details.

 

Figure 4
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  		Fig. 4. Mean (±SE) values for uncorrected Formula 2O2 (top), Formula 2O2/peak force (middle), and Formula 2O2/force-time integral (bottom) as a function of the time of contractions. The dashed lines indicate the asymptote of the fundamental component of the kinetics. See Formula 2O2 kinetics analysis for further details.

 
The amplitudes of the slow component-like response, expressed as a fraction of the total amplitudes of the Formula 2O2 responses, were significantly higher for Formula 2O2/peak force (0.18 ± 0.06) and for Formula 2O2/force-time integral (0.22 ± 0.05) compared with uncorrected Formula 2O2 (0.04 ± 0.04).

As for kinetics parameters related to the "fundamental" component of the Formula 2O2 kinetics, no significant differences were observed, for both the time delay (5.3 ± 0.5 s for uncorrected Formula 2O2, 5.1 ± 0.4 s for Formula 2O2/peak force, 5.6 ± 0.5 s for Formula 2O2/force-time integral) and the time-constant (15.7 ± 1.0 s for uncorrected Formula 2O2, 18.2 ± 1.7 s for Formula 2O2/peak force, 15.6 ± 1.4 s for Formula 2O2/force-time integral) between the three sets of data.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
In the original study (10) from which the data of the present analysis are derived, we occasionally observed a slow component of Formula 2O2 kinetics in maximally activated (by electrical stimulation) canine muscles in situ during 4-min contractions at ~60–70% of peak Formula 2O2. In that study, the muscle fatigued during the contraction period. In the present analysis, a slow component-like response of Formula 2O2 kinetics became a constant feature when the original Formula 2O2 values were normalized per unit of peak force or force-time. A critical issue of the present analysis is the following: can we consider what we observed, after normalizing Formula 2O2 per unit of force, a true slow component of Formula 2O2 kinetics? In strict terms no. During voluntary exercise in humans, a constant power output is maintained by increasing Formula 2O2; in our model, on the other hand, in the presence of a maximally activated muscle we observed a constant Formula 2O2 in the presence of a falling force output, that is a sort of "mirror image" of the slow component. For this reason in the present study we are mostly using the term "slow component-like response." Both observations have a common denominator, however, that is a decreased efficiency of muscle contraction. The novel observation deriving from the present study is that this reduced efficiency of muscle contraction, putative mechanism responsible for the slow component, is not necessarily related to a progressive recruitment of muscle fibers.

Both Barstow et al. (3) and Pringle et al. (26) observed that the amplitude of the slow component of Formula 2O2 kinetics is positively correlated with the percentage of type II fibers. Progressive recruitment of type II muscle fibers has been traditionally supported as the mechanism responsible for the "excess Formula 2O2" and the slow component of Formula 2O2 kinetics (5, 17, 38). According to this hypothesis, during constant-load heavy intensity exercise, some of the motor units recruited first may fatigue, eliciting a progressive recruitment of new motor units, which are probably composed more and more of type II muscle fibers. The evidence most cited in favor of this hypothesis, mainly obtained in animal studies, is that oxidative metabolism in type II fibers is characterized by a lower efficiency compared with type I fibers (4), which would explain the excess Formula 2O2 responsible for the Formula 2O2 slow component. Very few studies, however, have actually compared metabolic efficiency in type I and II fibers of human muscle. According to He et al. (15) peak thermodynamic efficiency is not significantly different between type I and type II or type IIA/IIX fibers, although peak efficiency is obtained in type I fibers at significantly lower load and speed of shortening. Evidence in favor and against a progressive recruitment of type II fibers as the mechanism responsible for the slow component of Formula 2O2 kinetics has been recently discussed in the review by Jones et al. (17). The newly recruited fibers may not necessarily be type II. According to Krustrup et al. (22) during exercise at 80% of Formula 2O2 max, in humans, both type I and type II fibers were recruited from the onset of exercise, and additional fibers (of both types) were recruited with time in temporal association with the development of the slow component of Formula 2O2 kinetics. Although a progressive recruitment of additional fibers likely occurs in other experimental models (22, 35), it was not possible in our model, in which all fibers were maximally activated from the onset of contractions. Nevertheless, after we normalized Formula 2O2 per unit of developed force or force-time, a slow component-like response of skeletal muscle Formula 2O2 kinetics became evident. Our results do not rule out the possibility that during voluntary exercise in exercising humans the slow component may be at least in part explained by progressive motor unit recruitment, but demonstrate that, at least in our isolated canine muscle preparation in situ, a slow component-like response of Formula 2O2 kinetics occurs even in the absence of a progressive recruitment of fibers.

As an alternative explanation for the slow component, the fatigued muscle could become less efficient as a direct consequence of fatigue itself (39). This phenomenon could explain the occurrence of the slow component independently from a sequential recruitment of fibers. The increased Formula 2O2/force (or force-time) ratio, and the associated slow component of Formula 2O2 kinetics, could evolve from factors related to the effects of fatigue on the initially recruited type II fibers (17). The muscles could become less efficient because they are approaching the metabolic characteristics of fatigue, such as a decrease in the Gibbs free energy of ATP hydrolysis, decreases in phosphocreatine and glycogen concentrations, as well as increases in [H+], [ADP], [Pi], [IMP], [NH3], etc. (6, 31, 32, 37, 39). The slow component of Formula 2O2 kinetics, then, could be associated with (or be a consequence of) a lower level of "metabolic stability" (41). Good metabolic stability during rest-to-work transition in skeletal muscle means less decrease in [PCr] and in the cytosolic phosphorylation potential, as well as less increase in [Pi], [ADPfree], [AMPfree], [IMPfree] for a given increase in Formula 2O2 (41). In the present study the exercise-induced increase in muscle Formula 2O2, from 0.4 ± 0.1 ml O2·100 g–1·min–1 at rest to 16.1 ± 1.6 ml O2·100 g–1·min–1 at the end of exercise, was accompanied by essentially no changes in ATP concentration (24.1 ± 1.0 vs. 23.6 ± 0.5 mmol/kg dry matter) and by a significant decrease in [PCr] (from 69.6 ± 3.8 to 41.7 ± 2.4 mmol/kg dry matter) (10). Interestingly, the 40-fold increase in Formula 2O2 was accompanied by only ~2.5-fold increase in the calculated [ADPfree], from 39.8 ± 1.0 µM at rest to 94.2 ± 9.4 µM at the end of the contraction period. Small relative increases in [ADPfree], in the presence of much greater relative increases in Formula 2O2, are typical for well-trained fatigue-resistant oxidative muscles (see e.g., Ref. 2, 16, 21, 41). In the present study, despite a relatively small disturbance in the muscle's metabolic stability, as suggested by the relatively small increase in [ADPfree], the magnitude of the slow component-like response of Formula 2O2 kinetics (after normalizing Formula 2O2 to force or force-time) was substantial, amounting to ~20–25% of the total Formula 2O2 response. This suggests that a slow component-like response of Formula 2O2 kinetics may occur also in muscles characterized by an elevated metabolic stability, in association with relatively small disturbances of the latter (41).

It has also been postulated that even a small decrease in the {Delta}GATP may affect the sarcoplasmic reticulum Ca2+ pump and prolong muscle relaxation time (18). This may lead to a rise in the resistance within the contractile machinery and contribute to the drop of muscle efficiency by increasing the internal work in the muscle (needing some extra ATP not used for the production of external mechanical power) and thus enhancement in the Formula 2O2/power output ratio (40). This concept would be in agreement with the growing body of evidence showing that the slow component in the Formula 2O2 kinetics is caused by a decreased efficiency of the contractile machinery (increase of the ATP/power output ratio) rather than by a decreased efficiency of the ATP production system (increase in the Formula 2O2/ATP ratio) (29, 40). According to Rossiter et al. (29), the slow component of Formula 2O2 kinetics is associated with a slow component of PCr kinetics, that is with an increased "phosphate cost" for force production, which would explain the reduced contractile efficiency.

Another possibility is that the reduced efficiency of muscle could result from the metabolic cost of recovery processes in fatigued fibers, which may contribute little, if any, to force or power output (forcing the muscle to recruit more motor units to keep force or power output constant). Despite a lack of force development, these fatigued fibers would consume O2 for Ca2+ and Na+/K+ pump activities, as hypothesized by previous authors (17, 27).

It must be recognized that the experimental model we used presents some limitations, which have been discussed at length in previous papers (10), and mainly refer to the intrinsic invasiveness of the preparation and to the pattern of muscle activation (synchronous tetanic contractions), which is quite different from that encountered in cycling or running, although it is similar to other common exercise paradigms, such as repeated maximal handgrip contractions. In the present study, however, maximal activation of all muscle fibers from the onset of the contraction period represented an advantage, since it excluded the possibility of a progressive recruitment of fibers during the contraction period.

The concept of a constant ATP turnover rate ("error signal"), which is usually implied in Formula 2O2 kinetics analysis, may not hold true in our model, in which the ATP turnover rate may decrease as a consequence of the decreased force output. On the other hand, the ATP turnover rate may increase as a function of the increased ATP cost for force production associated with fatigue. The net results of these two phenomena, going in opposite directions, is difficult to estimate. An increased ATP cost for force or power production, in the presence of a constant power output (that is, an increased error signal), would also apply to exercising humans, and is considered one of the causes (or the cause) of the slow components of PCr and Formula 2O2 kinetics.

Interestingly, our findings (that is, a substantially constant Formula 2O2 in the presence of a falling force output) appear compatible with observations in exercising humans. Stoudemire et al. (34), for example, observed that, to keep the rate of perceived exertion (and pulmonary Formula 2O2) constant from 15 to 30 min of exercise, subjects running on a treadmill progressively reduced the running speed. In that study, running speed corresponded, at the beginning of the exercise bout, to that associated during a preliminary incremental exercise to a blood lactate of 4 mM. Ribeiro et al. (28) reported that power output had to be reduced by ~15%, during 40 min of cycle ergometer exercise, to keep Formula 2O2 constant at ~80% of Formula 2O2max.

In conclusion, in isolated canine muscle in situ, during contractions corresponding to 60–70% of Formula 2O2 peak and in the absence of a progressive recruitment of muscle fibers, we observed a clear Formula 2O2 slow component-like response after Formula 2O2 data were normalized per unit of produced force. Thus a progressive recruitment of muscle fibers is not necessary for the development of the slow component of Formula 2O2 kinetics. We postulate that the slow component is caused by the metabolic factors that induce muscle fatigue and, as a consequence, reduce the efficiency of muscle contractions.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This study was supported in part by Agentia Spatiala Italiana-Osteoporosie Atrofia Muscolare Contract I/007/06/0 (Workpackage 1B-32) and by North Atlantic Treaty Organization Collaborative Linkage Grant 979220. J. A. Zoladz was also supported by funding from the Akademia Wychowania Fizycznego-Krakow for statutory research (2007).


   FOOTNOTES
 

Address for reprint requests and other correspondence: B. Grassi, Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi di Udine, Piazzale M. Kolbe 4, I-33100 Udine, Italy (e-mail: bgrassi{at}mail.dstb.uniud.it)

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
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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. Ameredes BT, Brechue WF, Stainsby WN. Mechanical and metabolic determination of Formula 2O2 and fatigue during repetitive isometric contractions in situ. J Appl Physiol 84: 1909–1916, 1998.[Abstract/Free Full Text]
  2. Balaban RS. Regulation of oxidative phosphorylation in the mammalian cell. Am J Physiol Cell Physiol 258: C377–C389, 1990.[Abstract/Free Full Text]
  3. Barstow TJ, Jones AM, Nguyen PH, Casaburi R. Influence of muscle fiber type and pedal frequency on oxygen uptake kinetics of heavy exercise. J Appl Physiol 81: 1642–1650, 1996.[Abstract/Free Full Text]
  4. Crow MT, Kushmerick MJ. Chemical energetics of slow- and fast-twitch muscles of the mouse. J Gen Physiol 79: 147–166, 1982.[Abstract/Free Full Text]
  5. Endo MY, Kobayakawa M, Kinugasa R, Kuno S, Akima H, Rossiter HB, Miura A, Fukuba Y. Thigh muscle activation distribution and pulmonary Formula 2O2 kinetics during moderate, heavy and very heavy intensity cycling exercise in humans. Am J Physiol Regul Integr Comp Physiol 293: R812–R820, 2007.[Abstract/Free Full Text]
  6. Fitts R. Cellular mechanisms of muscle fatigue. Physiol Rev 74: 49–94, 1994.[Abstract/Free Full Text]
  7. Gaesser GA, Poole DC. The slow component of oxygen uptake kinetics in humans. Exerc Sport Sci Rev 24: 35–71, 1996.[Medline]
  8. Grassi B, Gladden LB, Samaja M, Stary CM, Hogan MC. Faster adjustment of O2 delivery does not affect Formula 2O2 on-kinetics in isolated in situ canine muscle. J Appl Physiol 85: 1394–1403, 1998.[Abstract/Free Full Text]
  9. Grassi B, Gladden LB, Stary CM, Wagner PD, Hogan MC. Peripheral O2 diffusion does not affect Formula 2O2 on-kinetics in isolated in situ canine muscle. J Appl Physiol 85: 1404–1412, 1998.[Abstract/Free Full Text]
  10. Grassi B, Hogan MC, Greenhaff PL, Hamann JJ, Kelley KM, Aschenbach WG, Constantin-Teodosiu D, Gladden LB. Formula 2O2 on-kinetics in dog gastrocnemius in situ following activation of pyruvate dehydrogenase by dichloroacetate. J Physiol 538: 195–207, 2002.[Abstract/Free Full Text]
  11. Grassi B, Hogan MC, Kelley KM, Aschenbach WG, Hamann JJ, Evans RK, Patillo RE, Gladden LB. Role of convective O2 delivery in determining Formula 2O2 on-kinetics in canine muscle contracting at peak Formula 2O2. J Appl Physiol 89: 1293–1301, 2000.[Abstract/Free Full Text]
  12. Grassi B, Hogan MC, Kelley KM, Howlett RA, Gladden LB. Effects of NOS inhibition by L-NAME on oxygen uptake kinetics in isolated canine muscle in situ. J Physiol 568: 1021–1033, 2005.[Abstract/Free Full Text]
  13. Grassi B, Pogliaghi S, Rampichini S, Quaresima V, Ferrari M, Marconi C, Cerretelli P. Muscle oxygenation and gas exchange kinetics during cycling exercise on-transition in humans. J Appl Physiol 95: 149–158, 2003.[Abstract/Free Full Text]
  14. Harris RC, Hultman E, Nordesjö LO. Glycogen, glycolytic intermediates and high energy phosphates determined in biopsy samples of musculus femoris of man at rest. Methods and variance values. Scand J Clin Lab Inv 33: 109–120, 1974.[CrossRef]
  15. He ZH, Bottinelli R, Pellegrino MA, Ferenczi MA, Reggiani C. ATP consumption and efficiency of human single muscle fibres with different myosin isoform composition. Biophys J 79: 945–961, 2000.[Web of Science][Medline]
  16. Hochachka PW, McClelland GB. Cellular metabolic homeostasis during large-scale change in ATP turnover rates in muscles. J Exp Biol 200: 381–386, 1997.[Abstract]
  17. Jones AM, Pringle JSM, Carter E. Influence of muscle fibre type and motor unit recruitment on Formula 2O2 kinetics. In: Oxygen Uptake Kinetics in Sport, Exercise and Medicine, edited by Jones AM, Poole DC. London: Routledge, 2005, p. 261–293.
  18. Kammermeier H. Why do cells need phosphocreatine and a phosphocreatine shuttle. J Mol Cell Cardiol 19: 115–118, 1987.[CrossRef][Web of Science][Medline]
  19. Kelley KM, Hamann JJ, Aschenbach WG, Gladden LB. Canine gastrocnemius muscle in situ: Formula 2O2max (Abstract). Med Sci Sports Exerc 28: S62, 1996.[CrossRef]
  20. Kemp GJ, Roussel M, Bendahan D, Le Fur Y, Cozzone PJ. Interrelations of ATP synthesis and proton handling in ischaemically exercising human forearm muscle studied by 31P magnetic resonance spectroscopy. J Physiol 535: 901–928, 2001.[Abstract/Free Full Text]
  21. Korzeniewski B, Zoladz JA. Training-induced adaptation of oxidative phosphorylation in skeletal muscles. Biochem J 374: 37–40, 2003.[CrossRef][Web of Science][Medline]
  22. Krustrup P, Söderlund K, Mohr M, Bangsbo J. The slow component of oxygen uptake during intense, sub-maximal exercise in man is associated with additional fibre recruitment. Pflügers Arch 447: 855–866, 2004.[CrossRef][Web of Science][Medline]
  23. Linnarsson D. Dynamics of pulmonary gas exchange and heart rate changes at start and end of exercise. Acta Physiol Scand 415: 1–68, 1974.
  24. Ozyener F, Rossiter HB, Ward SA, Whipp BJ. Influence of exercise intensity on the on- and off- transient kinetics of pulmonary oxygen uptake in humans. J Physiol 533: 891–902, 2001.[Abstract/Free Full Text]
  25. Poole DC, Schaffartzik W, Knight DR, Derion T, Kennedy B, Guy HJ, Prediletto R, Wagner PD. Contribution of exercising legs to the slow component of oxygen uptake kinetics in humans. J Appl Physiol 71: 1245–1253, 1991.[Abstract/Free Full Text]
  26. Pringle JSM, Doust JH, Carter H, Tolfrey K, Campbell IT, Jones AM. Oxygen uptake kinetics during moderate, heavy and severe intensity "submaximal" exercise in humans: the influence of muscle fibre type and capillarisation. Eur J Appl Physiol 89: 289–300, 2003.[Web of Science][Medline]
  27. Pringle JSM, Doust JH, Carter H, Tolfrey K, Jones AM. Effect of pedal rate on primary and slow-component oxygen uptake responses during heavy-cycle exercise. J Appl Physiol 94: 1501–1507, 2003.[Abstract/Free Full Text]
  28. Ribeiro JP, Hughes V, Fielding RA, Holden W, Evans W, Knuttgen HG. Metabolic and ventilatory responses to steady state exercise relative to lactate thresholds. Eur J Appl Physiol 55: 215–221, 1986.[CrossRef][Web of Science]
  29. Rossiter HB, Ward SA, Kowalchuk JM, Howe FA, Griffiths JR, Whipp BJ. Dynamic asymmetry of phosphocreatine concentration and O2 uptake between the on- and off-transients of moderate- and high-intensity exercise in humans. J Physiol 541: 991–1002, 2002.[Abstract/Free Full Text]
  30. Sahlin K, Harris RC, Nylind B, Hultman E. Lactate content and pH in muscle obtained after dynamic exercise. Pflügers Arch 367: 143–149, 1976.[CrossRef][Web of Science][Medline]
  31. Sahlin K, Tonkonogi M, Soderlund K. Energy supply and muscle fatigue in humans. Acta Physiol Scand 162: 261–266, 1998.[CrossRef][Web of Science][Medline]
  32. Sargeant AJ, de Haan A. Human muscle fatigue: the significance of muscle fibre type variability studied using a micro-dissection approach. J Physiol Pharmacol 57, Suppl 10: 5–16, 2006.
  33. Stainsby WN, Welch HG. Lactate metabolism of contracting skeletal muscle in situ. Am J Physiol 211: 177–183, 1966.[Free Full Text]
  34. Stoudemire NM, Wideman L, Pass KA, McGinnes CL, Gaesser GA, Weltman A. The validity of regulating blood lactate concentration during running by ratings of perceived exertion. Med Sci Sports Exerc 28: 490–495, 1996.[Web of Science][Medline]
  35. Vøllestad NK, Vaage O, Hermansen L. Muscle glycogen depletion patterns in type I and subgroups of type II fibres during prolonged severe exercise in man. Acta Physiol Scand 122: 433–441, 1984.[Web of Science][Medline]
  36. Vøllestad NK, Wesche J, Sejersted OM. Gradual increase in leg oxygen uptake during repeated submaximal contractions in humans. J Appl Physiol 68: 1150–1156, 1990.[Abstract/Free Full Text]
  37. Westerblad H, Dahlstedt AJ, Lannergren J. Mechanisms underlying reduced maximum shortening velocity during fatigue of intact, single fibres of mouse muscle. J Physiol 510: 269–277, 1998.[Abstract/Free Full Text]
  38. Whipp BJ, Ward SA, Rossiter HB. Pulmonary O2 uptake during exercise: conflating muscular and cardiovascular responses. Med Sci Sports Exerc 37: 1574–1585, 2005.[CrossRef][Web of Science][Medline]
  39. Woledge RC. Possible effects of fatigue on muscle efficiency. Acta Physiol Scand 162: 267–273, 1998.[CrossRef][Web of Science][Medline]
  40. Zoladz JA, Korzeniewski B. Physiological background of the change point in O2 and the slow component of oxygen uptake kinetics. J Physiol Pharmacol 52: 167–184, 2001.[Web of Science][Medline]
  41. Zoladz JA, Korzeniewski B, Grassi B. Training-induced acceleration of oxygen uptake kinetics in skeletal muscle: the underlying mechanisms. J Physiol Pharmacol 57, Suppl 10: 67–84, 2006.



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