Kinetics of O₂ With Very High Intensity Exercise

The following is the abstract of the article discussed in the subsequent letter:

	ABSTRACT

Bangsbo, J., P. Krustrup, J. González-Alonso, R. Boushel, and B. Saltin. Muscle oxygen kinetics at onset of intense dynamic exercise in humans. Am J Physiol Regulatory Integrative Comp Physiol 279: R899-R906, 2000.The present study examined the onset and the rate of rise of muscle oxidation during intense exercise in humans and whether oxygen availability limits muscle oxygen uptake in the initial phase of intense exercise. Six subjects performed 3 min of intense one-legged knee-extensor exercise [65.3 ± 3.7 (means ± SE) W]. The femoral arteriovenous blood mean transit time (MTT) and time from femoral artery to muscle microcirculation was determined to allow for an examination of the oxygen uptake at capillary level. MTT was 15.3 ± 1.8 s and 4.7 ± 0.5 s at the end of exercise. Arterial venous O₂ difference (a-v_diff O₂) of 18 ± 5 ml/l before the exercise was unchanged after 2 s, but it increased (P < 0.05) after 6 s of exercise. Thigh oxygen uptake increased (P < 0.05) from 32 ± 8 to 102 ± 28 ml/min after 6 s of exercise and to 789 ± 88 ml/min at the end of exercise. The difference between thigh oxygen delivery (blood flow × arterial oxygen content) and thigh oxygen uptake increased (P < 0.05) after 6 s and returned to preexercise level after 14 s. The present data suggest that, at the onset of exercise, oxygen uptake of the exercising muscles increases after a delay of only a few seconds, and oxygen extraction peaks after ~50 s of exercise. The limited oxygen utilization in the initial phase of intense exercise is not caused by insufficient oxygen availability.

	LETTER

Kinetics of O₂ With Very High Intensity Exercise

To the Editor: In their study of O₂ uptake (O₂) at the onset of very high intensity leg exercise, Bangsbo and colleagues (1) provided important new information about the mean transit time for blood flow across the working leg muscles. However, the application of these data to interpretation of the kinetics of leg blood flow and muscle O₂ has not been applied correctly. As a consequence, statements about rate-limiting factors might not be correct.

The subjects in the study of Bangsbo et al. (1) completed single leg knee-extension exercise at an intensity that was selected to represent ~120% of the peak O₂ for this muscle group. Kinetics for O₂ and thigh blood flow were estimated as the time to achieve 50% of the end exercise response. As recently demonstrated, using the end exercise value as the "plateau" in exercise that exceeds peak O₂ causes an underestimation of the true kinetic time course (2). It is possible to use the data of Bangsbo and colleagues from their Fig. 4C to obtain an estimate of the thigh muscle O₂ kinetics. If the end exercise O₂ of 789 ml/min is taken as equivalent to 100% peak O₂ (the O₂ appeared to be still rising), then the estimated cost of the exercise would be ~947 ml/min. The time to achieve 50% of this "required O₂" would be ~35 s rather than the 25 s reported. Furthermore, the kinetic response is normally characterized by the time constant (time to achieve 63% of the required O₂), which was ~55 s, a value quite slow compared with submaximal exercise (2).

The significance of this new analysis of the time constant for O₂ at the onset of very high intensity exercise is that a very large portion of the required energy was not supplied from oxidative phosphorylation. For exercise at 120% O₂ peak, there must have been a large contribution from phosphocreatine stores and anaerobic glycolysis with lactate accumulation. Bangsbo et al. did not attempt to improve O₂ delivery after the onset of exercise, and thus it cannot be stated whether O₂ availability influenced O₂ kinetics. For knee-extension exercise, Richardson et al. (3) observed that the increase in intracellular PO₂ from 3 Torr during maximal exercise in normoxia to 4.1 Torr with hyperoxia was associated with a higher peak O₂. These levels of PO₂ can also be expected to modify metabolic control at the onset of exercise (4).

	REFERENCES

1.   Bangsbo, J, Krustrup P, González-Alonso J, Boushel R, and Saltin B. Muscle oxygen kinetics at onset of intense dynamic exercise in humans. Am J Physiol Regulatory Integrative Comp Physiol 279: R899-R906, 2000[Abstract/Free Full Text].

2.   Hughson, RL, O'Leary DD, Betik AC, and Hebestreit H. Kinetics of oxygen uptake at the onset of exercise near or above peak oxygen uptake. J Appl Physiol 88: 1812-1819, 2000[Abstract/Free Full Text].

3.   Richardson, RS, Leigh JS, Wagner PD, and Noyszewski EA. Cellular PO₂ as a determinant of maximal mitochondrial O₂ consumption in trained human skeletal muscle. J Appl Physiol 87: 325-331, 1999[Abstract/Free Full Text].

4.   Tschakovsky, ME, and Hughson RL. Interaction of factors determining oxygen uptake at the onset of exercise. J Appl Physiol 86: 1101-1113, 1999[Abstract/Free Full Text].

Richard L. Hughson, Department of Kinesiology University of Waterloo Waterloo, Ontario N2L 3G1, Canada

	REPLY

To the Editor: We appreciate Dr. Hughson's interest in our work (2) and his comments.

Dr. Hughson challenges our estimates of the O₂ kinetics at onset of exercise. He bases his criticism on data from experiments where pulmonary oxygen uptake has been measured. To what extent they apply to the present study, in which a small dynamically contracting muscle group was examined, is not immediately apparent. Anyway, it is of no value to estimate an imagined number (representing the total energy turnover) for an oxygen uptake level that cannot be reached. For example, the time constant t_1/2 for oxygen uptake would be infinite when the exercise intensity is higher than that corresponding to 200% of maximal oxygen uptake. The rate of rise in oxygen uptake during the present knee-extensor exercise should be related to the peak muscle oxygen uptake (as done in the article), which was not different from the maximum oxygen uptake of the muscle. t_1/2 for muscle oxygen uptake was 25 s, or, if one prefers, t_63% was 37 s. These values are not different from what is observed during submaximal exercise with the knee extensors. Muscle oxygen uptake is the product of blood flow and O₂ extraction (femoral arterial-venous O₂ difference) and one should look at these variables separately. O₂ extraction reaches a stable level during the course of the exercise. Thus there can be no doubt to which value the rate of change in O₂ extraction should be related. t_1/2 for O₂ extraction was 13 s and t_1/2 for thigh blood flow was 12 s, which are similar to what are observed for submaximal exercise.

The fact that the delay in increase in oxygen uptake, also at the muscle level, leads to a significant anaerobic energy turnover is not new. This is well described using the knee-extensor model, see for example Bangsbo et al. (1) and González-Alonso et al. (3), with precise measurements of the rate of anaerobic energy production as well as contribution of creatine phosphate and anaerobic glycolysis. Indeed what is new is that oxidative phosphorylation contributes both earlier and to a larger extent than has been anticipated. This leads us to the second point brought up by Dr. Hughson. Is oxygen available in the muscle cell and is it a limiting factor for oxygen uptake in the initial phase of exercise? With the design used in our study, the preexercise O₂ delivery was raised about fourfold (from ~80 to 320 ml/min) at onset of the voluntary work. We also know from the use of Doppler measurements of arterial inflow to dynamically contracting muscles that blood flow is elevated instantaneously after the first contraction. Thus it can be concluded that oxygen is available in ample amounts in the muscle capillaries before and immediately after onset of muscle contraction, which is confirmed by the observation that femoral venous oxygen content in the first 10 s of exercise was above 140 ml/l. It is, therefore, doubtful whether a further elevation in oxygen delivery or rise in oxygen gradient between blood and muscle cells would have had an effect on muscle oxygen uptake, but this issue was not examined in the present study. Dr. Hughson also brings up the study by Richardson et al. (4), which focused on the effect of hypoxia and hyperoxia on peak oxygen uptake during "maximal" exercise. The study does, however, not provide any information about what causes the limitation of oxygen uptake during the initial phase of exercise. It should also be mentioned that even though an advanced technique has been used to estimate myoglobin-associated PO₂ (P_MbO₂) in the study by Richardson et al. (4), the calculations have been suggested to underestimate P_MbO₂ (5). Nevertheless, P_MbO₂ values of 3-4 Torr are not believed to limit muscle respiration (6). Therefore, these data rather support the suggestion that there is sufficient oxygen available in the muscle cells during intense exercise.

	REFERENCES

1.   Bangsbo, J., Gollnick PD, Graham TE, Juel C, Kiens B, Mizuno M, and Saltin B. Anaerobic energy production and O₂ deficitdebt relationship during exhaustive exercise in humans. J Physiol (Lond) 422: 539-559, 1990[Abstract/Free Full Text].

2.   Bangsbo, J, Krustrup P, González-Alonso J, Boushel R, and Saltin B. Muscle oxygen kinetics at onset of intense dynamic exercise in humans. Am J Physiol Regulatory Integrative Comp Physiol 279: R899-R906, 2000.

3.   González-Alonso, J, Quistorff B, Krustrup P, Bangsbo J, and Saltin B. Heat production in human skeletal muscle at the onset of intense dynamic exercise. J Physiol (Lond) 524: 603-615, 2000[Abstract/Free Full Text].

4.   Richardson, RS, Leigh JS, Wagner PD, and Noyszewski EA. Cellular PO₂ as determinant of maximal mitochondiral O₂ consumption in trained human skeletal muscle. J Appl Physiol 87: 325-331, 1999.

5.   Tran, T-K, Sailasuta N, Kreutzer U, Hurd R, Chung Y, Mole P, Kuno S, and Jue T. Comparative analysis of NMR and NIRS measurements of intracellular PO₂ in human skeletal muscle. Am J Physiol Regulatory Integrative Comp Physiol 276: R1682-R1690, 1999[Abstract/Free Full Text].

6.   Wilson, DF, and Rumsey WL. Factors modulating the oxygen dependence of mitochondrial oxidative phosphorylation. Adv Exp Med Biol 222: 121-131, 1988[Medline].

Jens Bangsbo, Peter Krustrup, José González-Alonso, Robert Boushel, Bengt Saltin, The August Krogh Institute Copenhagen, Denmark DK-2100