Brian J. Whipp

Influence of exercise intensity on the on- and off-transient kinetics of pulmonary oxygen uptake in humans

1 The maximal oxygen uptake (V̇O2,peak) during dynamic muscular exercise is commonly taken as a crucial determinant of the ability to sustain high‐intensity exercise. Considerably less attention, however, has been given to the rate at which V̇O2 increases to attain this maximum (or to its submaximal requirement), and even less to the kinetic features of the response following exercise. 2 Six, healthy, male volunteers (aged 22 to 58 years), each performed 13 exercise tests: initial ramp‐incremental cycle ergometry to the limit of tolerance and subsequently, on different days, three bouts of square‐wave exercise each at moderate, heavy, very heavy and severe intensities. Pulmonary gas exchange variables were determined breath by breath throughout exercise and recovery from the continuous monitoring of respired volumes (turbine) and gas concentrations (mass spectrometer). 3 For moderate exercise, the V̇O2 kinetics were well described by a simple mono‐exponential function, following a short cardiodynamic phase, with the on‐ and off‐transients having similar time constants (τ1); i.e. τ1,on averaged 33 ± 16 s (± S.D.) and τ1,off 29 ± 6 s. 4 The on‐transient V̇O2 kinetics were more complex for heavy exercise. The inclusion of a second slow and delayed exponential component provided an adequate description of the response; i.e. τ1,on= 32 ± 17 s and τ2,on= 170 ± 49 s. The off‐transient V̇O2 kinetics, however, remained mono‐exponential (τ1,off= 42 ± 11 s). 5 For very heavy exercise, the on‐transient V̇O2 kinetics were also well described by a double exponential function (τ1,on= 34 ± 11 s and τ2,on= 163 ± 46 s). However, a double exponential, with no delay, was required to characterise the off‐transient kinetics (i.e. τ1,off= 33 ± 5 s and τ2,off= 460 ± 123 s). 6 At the highest intensity (severe), the on‐transient V̇O2 kinetics reverted to a mono‐exponential profile (τ1,on= 34 ± 7 s), while the off‐transient kinetics retained a two‐component form (τ1,off= 35 ± 11 s and τ2,off= 539 ± 379 s). 7 We therefore conclude that the kinetics of V̇O2 during dynamic muscular exercise are strikingly influenced by the exercise intensity, both with respect to model order and to dynamic asymmetries between the on‐ and off‐transient responses.

Dynamic asymmetry of phosphocreatine concentration and O2 uptake between the on- and off-transients of moderate- and high-intensity exercise in humans

The on‐ and off‐transient (i.e. phase II) responses of pulmonary oxygen uptake (V̇O2) to moderate‐intensity exercise (i.e. below the lactate threshold, θL) in humans has been shown to conform to both mono‐exponentiality and ‘on‐off’ symmetry, consistent with a system manifesting linear control dynamics. However above θL the V̇O2 kinetics have been shown to be more complex: during high‐intensity exercise neither mono‐exponentiality nor ‘on‐off’ symmetry have been shown to appropriately characterise the V̇O2 response. Muscle [phosphocreatine] ([PCr]) responses to exercise, however, have been proposed to be dynamically linear with respect to work rate, and to demonstrate ‘on‐off’ symmetry at all work intenisties. We were therefore interested in examining the kinetic characteristics of the V̇O2 and [PCr] responses to moderate‐ and high‐intensity knee‐extensor exercise in order to improve our understanding of the factors involved in the putative phosphate‐linked control of muscle oxygen consumption. We estimated the dynamics of intramuscular [PCr] simultaneously with those of V̇O2 in nine healthy males who performed repeated bouts of both moderate‐ and high‐intensity square‐wave, knee‐extension exercise for 6 min, inside a whole‐body magnetic resonance spectroscopy (MRS) system. A transmit‐receive surface coil placed under the right quadriceps muscle allowed estimation of intramuscular [PCr]; V̇O2 was measured breath‐by‐breath using a custom‐designed turbine and a mass spectrometer system. For moderate exercise, the kinetics were well described by a simple mono‐exponential function (following a short cardiodynamic phase for V̇O2,), with time constants (τ) averaging: τV̇O2,on 35 ± 14 s (±s.d.), τ[PCr]on 33 ± 12 s, τV̇O2,off 50 ± 13 s and τ[PCr]off 51 ± 13 s. The kinetics for both V̇O2 and [PCr] were more complex for high‐intensity exercise. The fundamental phase expressing average τ values of τV̇O2,on 39 ± 4 s, τ[PCr]on 38 ± 11 s, τV̇O2,off 51 ± 6 s and τ[PCr]off 47 ± 11 s. An associated slow component was expressed in the on‐transient only for both V̇O2 and [PCr], and averaged 15.3 ± 5.4 and 13.9 ± 9.1 % of the fundamental amplitudes for V̇O2 and [PCr], respectively. In conclusion, the τ values of the fundamental component of [PCr] and V̇O2 dynamics cohere to within 10 %, during both the on‐ and off‐transients to a constant‐load work rate of both moderate‐ and high‐intensity exercise. On average, ≈90 % of the magnitude of the V̇O2 slow component during high‐intensity exercise is reflected within the exercising muscle by its [PCr] response.

Inferences from pulmonary O2 uptake with respect to intramuscular [phosphocreatine] kinetics during moderate exercise in humans

1 In the non‐steady state of moderate intensity exercise, pulmonary O2 uptake (V̇p,O2) is temporally dissociated from muscle O2 consumption (V̇m,O2) due to the influence of the intervening venous blood volume and the contribution of body O2 stores to ATP synthesis. A monoexponential model of V̇p,O2 without a delay term, therefore, implies an obligatory slowing of V̇p,O2 kinetics in comparison to V̇m,O2. 2 During moderate exercise, an association of V̇m,O2 and [phosphocreatine] ([PCr]) kinetics is a necessary consequence of the control of muscular oxidative phosphorylation mediated by some function of [PCr]. It has also been suggested that the kinetics of V̇p,O2 will be expressed with a time constant within 10 % of that of V̇m,O2. 3 V̇p,O2 and intramuscular [PCr] kinetics were investigated simultaneously during moderate exercise of a large muscle mass in a whole‐body NMR spectrometer. Six healthy males performed prone constant‐load quadriceps exercise. A transmit‐receive coil under the right quadriceps allowed determination of intramuscular [PCr]; V̇p,O2 was measured breath‐by‐breath, in concert with [PCr], using a turbine and a mass spectrometer system. 4 Intramuscular [PCr] decreased monoexponentially with no delay in response to exercise. The mean of the time constants (τPCr) was 35 s (range, 20–64 s) for the six subjects. 5 Two temporal phases were evident in the V̇p,O2 response. When the entire V̇p,O2 response was modelled to be exponential with no delay, its time constant (τ′V̇p,O2) was longer in all subjects (group mean = 62 s; range, 52–92 s) than that of [PCr], reflecting the energy contribution of the O2 stores. 6 Restricting the V̇p,O2 model fit to phase II resulted in matching kinetics for V̇p,O2 (group mean τV̇p,O2= 36 s; range, 20–68 s) and [PCr], for all subjects. 7 We conclude that during moderate intensity exercise the phase II τV̇p,O2 provides a good estimate of τPCr and by implication that of V̇m,O2 (τV̇m,O2).

Effects of prior exercise on oxygen uptake and phosphocreatine kinetics during high‐intensity knee‐extension exercise in humans

1 A prior bout of high‐intensity square‐wave exercise can increase the temporal adaptation of pulmonary oxygen uptake (V̇O2) to a subsequent bout of high‐intensity exercise. The mechanisms controlling this adaptation, however, are poorly understood. 2 We therefore determined the dynamics of intramuscular [phosphocreatine] ([PCr]) simultaneously with those of V̇O2 in seven males who performed two consecutive bouts of high‐intensity square‐wave, knee‐extensor exercise in the prone position for 6 min with a 6 min rest interval. A magnetic resonance spectroscopy (MRS) transmit‐receive surface coil under the quadriceps muscle allowed estimation of [PCr]; V̇O2 was measured breath‐by‐breath using a custom‐designed turbine and a mass spectrometer system. 3 The V̇O2 kinetics of the second exercise bout were altered compared with the first such that (a) not only was the instantaneous rate of V̇O2 change (at a given level of V̇O2) greater but the phase II τ was also reduced ‐ averaging 46.6 ± 6.0 s (bout 1) and 40.7 ± 8.4 s (bout 2) (mean ±s.d.) and (b) the magnitude of the later slow component was reduced. 4 This was associated with a reduction of, on average, 16.1 % in the total exercise‐induced [PCr] decrement over the 6 min of the exercise, of which 4.0 % was due to a reduction in the slow component of [PCr]. There was no discernable alteration in the initial rate of [PCr] change. The prior exercise, therefore, changed the multi‐compartment behaviour towards that of functionally first‐order dynamics. 5 These observations demonstrate that the V̇O2 responses relative to the work rate input for high‐intensity exercise are non‐linear, as are, it appears, the putative phosphate‐linked controllers for which [PCr] serves as a surrogate.

Utility of cardiopulmonary exercise in the assessment of clinical determinants of functional capacity in hypertrophic cardiomyopathy.

The utility of metabolic gas exchange measurements in evaluating the severity and determinants of exercise limitation was studied during upright symptom-limited cardiopulmonary exercise in 135 consecutive patients with hypertrophic cardiomyopathy (HC) and 50 healthy age- and gender-matched volunteers. Peak oxygen consumption (VO(2)) was less than predicted (age, gender, and size) in 99% patients. Peak VO(2) was significantly associated with New York Heart Association functional class; however, there was considerable overlap of peak VO(2) between classes I and III (70 +/- 15%, 56 +/- 15%, 35 +/- 11%, respectively). Patients with abnormal blood pressure responses and patients with chronotropic incompetence during exercise had lower percent-predicted peak VO(2) than patients with normal blood pressure and heart rate responses during exercise (p = 0.0001 and p <0.001, respectively). Percent-predicted peak VO(2) was similar in patients with and without resting left ventricular outflow obstruction. Of those patients with resting gradients, however, there was a strong inverse correlation between the magnitude of the gradient and peak VO(2) (r = 0.5; p <0.001). In conclusion, peak VO(2) is significantly related to New York Heart Association functional class in this group of patients with HC, but peak VO(2) is a superior measure of cardiovascular performance in individual patients. Our peak VO(2) data indicate that mechanical obstruction has an adverse pathophysiologic effect on functional capacity and provide the rationale to support treatments aimed at gradient reduction. Low peak VO(2) characteristics including those with normal or near-normal left ventricular wall thickness suggests that measurement of peak VO(2) may aid in the differential diagnosis between HC and athletes heart.

Effect of prior metabolic rate on the kinetics of oxygen uptake during moderate-intensity exercise.

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The effect of resistive breathing on leg muscle oxygenation using near-infrared spectroscopy during exercise in men

dot V{rm O}_{rm 2}

Cardiopulmonary responses to exercise in patients with hypertrophic cardiomyopathy

n) dynamics during moderate-intensity exercise are often assumed to be dynamically linear (i.e. neither the gain nor the time constant (τ) of the response varies as a function of work rate). However, faster, slower and unchanged % MathType!MTEF!2!1!+-n% feaaeaart1ev0aqatCvAUfKttLearuavP1wzZbqedmvETj2BSbWexLn% MBbXgBcf2CPn2qVrwzqf2zLnharyWqVvNCPvMCG4uz3bqee0evGueEn% 0jxyaibaieYlf9irVeeu0dXdh9vqqj-hEeeu0xXdbba9frFj0-OqFfn% ea0dXdd9vqaq-JfrVkFHe9pgea0dXdar-Jb9hs0dXdbPYxe9vr0-vrn% 0-vqpWqaaeaabiGaciaacaqabeaadaqaaqaaaOqaaiqbdAfawzaacan% Gaee4ta80aaSbaaSqaaiabbkdaYaqabaaaaa!386A!

Effect of recovery duration from prior exhaustive exercise on the parameters of the power-duration relationship

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Intersample fluctuations in phosphocreatine concentration determined by 31P-magnetic resonance spectroscopy and parameter estimation of metabolic responses to exercise in humans

n kinetics have been reported during work-to-work transitions compared to rest-to-work transitions, all within the moderate-intensity domain. In an attempt to resolve these discrepancies and to improve the confidence of the parameter estimation, we determined the % MathType!MTEF!2!1!+-n% feaaeaart1ev0aqatCvAUfKttLearuavP1wzZbqedmvETj2BSbWexLn% MBbXgBcf2CPn2qVrwzqf2zLnharyWqVvNCPvMCG4uz3bqee0evGueEn% 0jxyaibaieYlf9irVeeu0dXdh9vqqj-hEeeu0xXdbba9frFj0-OqFfn% ea0dXdd9vqaq-JfrVkFHe9pgea0dXdar-Jb9hs0dXdbPYxe9vr0-vrn% 0-vqpWqaaeaabiGaciaacaqabeaadaqaaqaaaOqaaiqbdAfawzaacan% Gaee4ta80aaSbaaSqaaiabbkdaYaqabaaaaa!386A!