The algorithm used for the calculation of gas exchange affects the estimation of O2 uptake kinetics at the onset of moderate-intensity exercise.

At the start of a moderate-intensity square-wave exercise, after a short delay, breath-by-breath O2 uptake at the mouth is approximated to a mono-exponential function, whose time constant is considered matched to that of the O2 uptake of the working muscles. We compared the kinetic parameters obtained from the breath-by-breath gas exchange data yielded by the 'Independent-breath' algorithm (IND), which accounts for the changes in lung gas stores, with those obtained with the classical 'Expiration-only' algorithm (EXP). The two algorithms were applied on the same flow and gas fraction traces acquired on 10 healthy volunteers, performing 10 times the same moderate-intensity exercise transition. Repeated O2 uptake responses were stacked together and the kinetic parameters of a mono-exponential function were estimated by non-linear regression, removing the data pertaining to 1-s progressively longer initial periods (ΔTr ). Independently of ΔTr , the mean response time (time constant + time delay) obtained for the IND data was faster compared to the EXP data (∼43 s vs. ∼47 s, P < 0.001), essentially because of shorter time delays. Between ΔTr  = 16 s and ΔTr  = 29s, the time constants of the IND data decreased (30.7 s vs. 28.0 s, P < 0.05; drop = 10%), but less than those of the EXP data (32.2 s vs. 26.2 s, P < 0.001; drop = 23%); with the same ΔTr , the time constants of the two algorithms' data were not different (P > 0.07). The different decrease in the time constant, together with the different mean response time, suggests that the data yielded by the two algorithms provide a different picture of the phenomena occurring at the beginning of the exercise.

Influence of the fitting window on the O2 uptake kinetics at the onset of moderate intensity exercise.

The O2 uptake (V̇o2) data at the onset of an exercise are usually fitted with a mono-exponential function, after removal of the data pertaining to a conventional initial time period (ΔTr) lasting ∼20 s. We performed a thorough quantitative analysis on the effects of removing data pertaining to different ΔTr, aiming at identifying an objective method to establish the appropriate ΔTr. Breath-by-breath O2 uptake responses, acquired from 25 healthy adults performing a step moderate-intensity exercise, and 104 simulated biexponential responses, were analyzed. For all the responses, the kinetic parameters of a mono-exponential function and the corresponding asymptotic standard errors (ASEs) were estimated by nonlinear regression, removing the data pertaining to progressively longer initial periods (1 s each) up to 60 s. Four methods to establish objectively ΔTr were compared. The minimum estimated τ was obtained for ΔTr ≅ 35 s in both the V̇o2 and simulated data, that was about 30% lower compared with that obtained for ΔTr ≅ 0s. The average ASE values remained quite constant up to ΔTr ≅ 35 s, thereafter they increased remarkably. The τ used to generate the simulated response fell within the confidence intervals of the estimated τ in ∼85% of cases for ΔTr = 20 s ("20 s-w" method); this percentage increased to ∼92% of cases when ΔTr was established according to both the minimum τ and its narrowest confidence interval ("Mixed" method). In conclusion, the effects of removing V̇o2 data pertaining to different ΔTr are remarkable. The "Mixed" method provided estimated parameters close to those used to generate the simulated responses and is thus endorsed.NEW & NOTEWORTHY We propose a method to objectively establish the initial time period to be removed from the fitting window when, using a mono-exponential model, the kinetics of the fundamental component is determined on breath-by-breath O2 uptake data collected at the onset of a moderate-intensity exercise. Innovative statistical parameters ("Coverage" and "Concordance5%," applicable on simulated responses) were used to compare its performance with that of other three methods. The proposed method yielded the best "Coverage" and "Concordance5%."

Interchangeability between two breath-by-breath O2 uptake calculation algorithms in asthmatic and healthy volunteers.

INTRODUCTION: The interchangeability analysis has been recently proposed to objectively assess whether a newly developed measurement tool can substitute the older ones; this analysis assumes that the measures yielded by the compared tools should differ less than a maximum acceptable value. We aimed to assess the interchangeability rate (IR) of the breath-by-breath O2 uptake data calculated with the "Independent breath" (IND) and the "Expiration-only" (EXP) algorithms. METHODS: Oxygen, carbon dioxide fractions, and ventilatory flow were recorded continuously over 26 min in 18 asthmatic and 20 well-matched healthy volunteers at rest, during cycling, and recovery; oxygen uptake (V'O2) was calculated with the two algorithms under comparison. Coefficients of variation (CVs) of all the steady-state condition were modeled as a function of the average V'O2 values and IR was calculated accordingly. RESULTS: CVs were significantly greater in the asthmatic volunteers (F = 5.97, p < 0.05), being lower for IND compared to EXP (F > 7.04, p < 0.02). CVs decreased as a function of the reciprocal of the square root of the average V'O2. The IR, calculated on the basis of this relationship, was not significantly different in the two groups of volunteers (F = 0.77, p = 0.385); taking as reference method the IND, or EXP algorithms, the IR values were significantly different (F = 58.6, p < 0.001), amounting to 97.4 ± 2.2% or to 98.2 ± 1.7%, respectively. CONCLUSION: The relative noise of V'O2 was greater in the asthmatic volunteers compared to the healthy ones and was lower for IND compared to EXP. The interchangeability analysis suggested that IND might be a better substitute for EXP than the opposite.

Breath-by-breath oxygen uptake during running: Effects of different calculation algorithms.

NEW FINDINGS: What is the central question of this study? Breath-by-breath gas exchange analysis during treadmill exercise can be disturbed by different breathing patterns depending on cadence, and the flow sensor might be subjected to variable mechanical stress. It is still unclear whether the outcomes of the gas exchange algorithms can be affected by running at different speeds. What is the main finding and its importance? Practically, the three investigated breath-by-breath algorithms ('Wessel', 'expiration-only' and 'independent breath') provided similar average gas exchange values for steady-state conditions. The 'independent breath' algorithm showed the lowest breath-by-breath fluctuations in the gas exchange data compared with the other investigated algorithms, both at steady state and during incremental exercise. ABSTRACT: Recently, a new breath-by-breath gas exchange calculation algorithm (called 'independent breath') was proposed. In the present work, we aimed to compare the breath-by-breath O2 uptake ( V̇O2 ) values assessed in healthy subjects undergoing a running protocol, as calculated applying the 'independent breath' algorithm or two other commonly used algorithms. The traces of respiratory flow, O2 and CO2 fractions, used by the calculation algorithms, were acquired at the mouth on 17 volunteers at rest, during running on a treadmill at 6.5 and 9.5 km h-1 , and thereafter up to volitional fatigue. Within-subject averages and standard deviations of breath-by-breath V̇O2 were calculated for steady-state conditions; the V̇O2 data of the incremental phase were analysed by means of linear regression, and their root mean square was assumed to be an index of the breath-by-breath fluctuations. The average values obtained with the different algorithms were significantly different (P < 0.001); nevertheless, from a practical point of view the difference could be considered 'small' in all the investigated conditions (effect size <0.3). The standard deviations were significantly lower for the 'independent breath' algorithm (post hoc contrasts, P < 0.001), and the slopes of the relationships with the corresponding data yielded by the other algorithms were <0.70. The root mean squares of the linear regressions calculated for the incremental phase were also significantly lower for the 'independent breath' algorithm, and the slopes of the regression lines with the corresponding values obtained with the other algorithms were <0.84. In conclusion, the 'independent breath' algorithm yielded the least breath-by-breath O2 uptake fluctuation, both during steady-state exercise and during incremental running.

Comparison of different breath-by-breath gas exchange algorithms using a gas exchange simulation system.

BACKGROUND: Mechanical Gas Exchange Simulation Systems (GESS) have never been used to compare different breath-by-breath oxygen uptake calculation algorithms. METHODS: Oxygen uptakes were calculated for each GESS cycle by the "Expiration-only" algorithm (estimating inspiratory volume from the expiratory one), and by two "alveolar" algorithms (both processing inspiratory and expiratory flows and designed to account for the changes in lung gas stores). The volume of oxygen stored in the GESS from one cycle to the subsequent one was either maintained constant or increased/decreased by changing the pumped gas volumes. RESULTS: Overlapping oxygen uptakes were obtained maintaining constant the volume of oxygen stored (grand average: 0.420 ± 0.019 L/min, p = ns). The "Expiration-only" algorithm overestimated the decreases of the stored oxygen by 34%, whereas the "alveolar" algorithms underestimated the increases by 25%; in the other conditions, the changes of the stored oxygen were appropriately accounted for. CONCLUSIONS: The use of "alveolar" algorithms is recommended, particularly so when abrupt changes in the stored oxygen volume occur.

The "independent breath" algorithm: assessment of oxygen uptake during exercise.

PURPOSE: Reduction of noise of breath-by-breath gas-exchange data is crucial to improve measurements. A recently described algorithm ("independent breath"), that neglects the contiguity in time of breaths, was tested. METHODS: Oxygen, carbon dioxide fractions, and ventilatory flow were recorded continuously over 26 min in 20 healthy volunteers at rest, during unloaded and moderate intensity cycling and subsequent recovery; oxygen uptake ([Formula: see text]) was calculated with the "independent breath" algorithm (IND) and, for comparison, with three other "classical" algorithms. Average [Formula: see text] and standard deviations were calculated for steady-state conditions; non-linear regression was run throughout the [Formula: see text] data of the transient phases (ON and OFF), using a mono-exponential function. RESULTS: Comparisons of the different algorithms showed that they yielded similar average [Formula: see text] at steady state (p = NS). The standard deviations were significantly lower for IND (post hoc contrasts, p < 0.001), with the slope of the relationship with the corresponding data obtained from "classical" algorithms being < 0.69. For both transients, the overall kinetics (evaluated as time delay + time constant) was significantly faster for IND (post hoc contrasts, p < 0.001). For the ON transient, the asymptotic standard errors of the kinetic parameters were significantly lower for IND, with the slope of the regression line with the corresponding values obtained from the "classical" algorithms being < 0.60. CONCLUSION: The "independent breath" algorithm provided consistent average O2 uptake values while reducing the overall noise of about 30%, which might result in the halving of the required number of repeated trials needed to assess the kinetic parameters of the ON transient.

Calculation algorithms for breath-by-breath alveolar gas exchange: the unknowns!

PURPOSE: Several papers (algorithm papers) describe computational algorithms that assess alveolar breath-by-breath gas exchange by accounting for changes in lung gas stores. It is unclear, however, if the effects of the latter are actually considered in literature. We evaluated dissemination of algorithm papers and the relevant provided information. METHODS: The list of documents investigating exercise transients (in 1998-2017) was extracted from Scopus database. Documents citing the algorithm papers in the same period were analyzed in full text to check consistency of the relevant information provided. RESULTS: Less than 8% (121/1522) of documents dealing with exercise transients cited at least one algorithm paper; the paper of Beaver et al. (J Appl Physiol 51:1662-1675, 1981) was cited most often, with others being cited tenfold less. Among the documents citing the algorithm paper of Beaver et al. (J Appl Physiol 51:1662-1675, 1981) (N = 251), only 176 cited it for the application of their algorithm/s; in turn, 61% (107/176) of them stated the alveolar breath-by-breath gas exchange measurement, but only 1% (1/107) of the latter also reported the assessment of volunteers' functional residual capacity, a crucial parameter for the application of the algorithm. Information related to gas exchange was provided consistently in the methods and in the results in 1 of the 107 documents. CONCLUSION: Dissemination of algorithm papers in literature investigating exercise transients is by far narrower than expected. The information provided about the actual application of gas exchange algorithms is often inadequate and/or ambiguous. Some guidelines are provided that can help to improve the quality of future publications in the field.

Assessing breath-by-breath alveolar gas exchange: is the contiguity in time of breaths mandatory?

PURPOSE: A new algorithm is illustrated for the determination of breath-by-breath alveolar gas exchange that neglects the contiguity in time of breaths, i.e. it allows the breaths to be partially superimposed or disjoined in time. METHODS: Traces of oxygen, carbon dioxide fractions, and ventilatory flow were recorded continuously over 20 min in 15 healthy subjects in resting conditions; at 5-min intervals, subjects voluntarily hyperventilated for ~ 30 s to induce abrupt changes in lung gas stores. Gas exchange data were calculated applying the new algorithm and were compared to those yielded by a reference algorithm, also providing values at the alveolar level. RESULTS: Average O2 uptakes (V'O2) obtained with the two algorithms were similar during quiet breathing (0.28 ± 0.06 vs. 0.29 ± 0.06 L/min; two-sided paired t test, n = 45, p = NS); during hyperventilation, average V'O2 was significantly lower applying the new algorithm compared to the reference algorithm (0.57 ± 0.15 vs. 0.65 ± 0.17 L/min; difference - 0.077 ± 0.048 L/min; two-sided paired t test, n = 45, p < 0.001). The first breath of each hyperventilation manoeuvre showed the greatest difference in V'O2 (- 0.25 ± 0.23 L/min, z test against zero, n = 45, p < 0.001). The volumes of O2 considered twice (or neglected) because of the lack of contiguity of breaths were overall small (maximum of 3 mL) and, if accounted for, had only a slight softening effect on the fluctuations of the O2 uptake. CONCLUSION: The new algorithm, which assumes each breath as the leading subject, was able to effectively account for changes in lung gas stores without requiring any predetermined value or off-line optimisation procedure.

Calculation algorithms alter the breath-by-breath gas exchange values when abrupt changes in ventilation occur.

The automatic metabolic units calculate breath-by-breath gas exchange from the expiratory data only, applying an algorithm ('expiration-only' algorithm) that neglects the changes in the lung gas stores. These last are theoretically taken into account by a recently proposed algorithm, based on an alternative view of the respiratory cycle ('alternative respiratory cycle' algorithm). The performance of the two algorithms was investigated where changes in the lung gas stores were induced by abrupt increases in ventilation above the physiological demand. Oxygen, carbon dioxide fractions and ventilatory flow were recorded at the mouth in 15 healthy subjects during quiet breathing and during 20-s hyperventilation manoeuvres performed at 5-min intervals in resting conditions. Oxygen uptakes and carbon dioxide exhalations were calculated throughout the acquisition periods by the two algorithms. Average ventilation amounted to 6·1 ± 1·4 l min-1 during quiet breathing and increased to 41·8 ± 27·2 l min-1 during the manoeuvres (P<0·01). During quiet breathing, the two algorithms provided overlapping gas exchange data and noise. Conversely, during hyperventilation, the 'alternative respiratory cycle' algorithm provided significantly lower gas exchange data as compared to the values yielded by the 'expiration-only' algorithm. For the first breath of hyperventilation, the average values provided by the two algorithms amounted to 0·37 ± 0·34 l min-1 versus 0·96 ± 0·73 l min-1 for O2 uptake and 0·45 ± 0·36 l min-1 versus 0·80 ± 0·58 l min-1 for exhaled CO2 (P<0·001 for both). When abrupt increases in ventilation occurred, such as those arising from a deep breath, the 'alternative respiratory cycle' algorithm was able to halve the artefactual gas exchange values as compared to the 'expiration-only' approach.

Influence of phosphagen concentration on phosphocreatine breakdown kinetics. Data from human gastrocnemius muscle.

At the onset of a square-wave exercise of moderate intensity, in the absence of any detectable lactate production, the hydrolysis of phosphocreatine (PCr) fills the gap between energy requirement and energy yield by oxidative pathways, thus representing a readily available source of energy for the muscle. We verified experimentally the relationships between high-energy phosphates and/or their changes and the time constant of PCr concentration ([PCr]) kinetics in humans (tau(PCr)). High-energy phosphate concentration (by (31)P-NMR spectroscopy) in the calf muscles were measured during three repetitions of the rest-to-work transition of moderate aerobic square-wave exercise on nine healthy volunteers, while resting [PCr] was estimated from the appropriate spectroscopy data. PCr concentration decreased significantly (22 +/- 6%) from rest to steady-state exercise, without differences among the three repetitions. Absolute resting [PCr] and tau(PCr) were consistent with literature values, amounting to 27.5 +/- 2.2 mM and 23.9 +/- 2.9 s, respectively. No significant relationships were detected between individual tau(PCr) and mechanical power, fraction or absolute amount of PCr hydrolyzed, or change in ADP concentration. On the contrary, individual tau(PCr) (s) was linearly related to absolute resting [PCr] (mM), the relationship being described by: tau(PCr) = 0.656 + 0.841.[PCr] (n = 9, R = 0.708, P < 0.05). These data support the view that in humans PCr concentration sets the time course of the oxidative metabolism in skeletal muscle at the start of exercise, being one of the main controllers of oxidative phosphorylation.

Vastus lateralis O2 desaturation in response to fast and short maximal contraction.

PURPOSE: The purpose of this study was to investigate, in heavy-resistance strength-trained (N = 10) and untrained (N = 10) subjects, the vastus lateralis muscle oxyhemoglobin (O2Hb) desaturation time course in response to a brief, maximal, voluntary isometric contraction. METHODS: The two groups were not statistically different physically. Mean (+/- SD) age, height, and body mass of all the subjects were 28.0 +/- 6.3 yr, 1.8 +/- 0.1 m, and 77.8 +/- 9.9 kg, respectively. Each subject performed five trials. Every trial consisted of 1) a 1-min rest period, 2) a leg press exercise of 2-4 s, and 3) a 5-min recovery period. Leg press exercise consisted of a static maximal voluntary contraction performed using the dominant leg only. Leg press strength was recorded using a load cell. Muscle O2Hb saturation (SmO2) was measured noninvasively by near-infrared spectroscopy (0.17-s sampling time). RESULTS: Rate of force development was higher in the trained subjects than in the untrained ones (6897 +/- 1654 vs 5515 +/- 1434 N x s(-1); P < 0.05). Once the exercise began, the time to the onset of SmO2 decrease was consistently shorter in the untrained than in the trained subjects (2.81 +/- 0.40 vs 3.91 +/- 0.67 s, P < 0.01). In all the trained subjects and in two of the untrained ones, SmO2 started to decrease once the exercise was stopped. After the end of the exercise, SmO2 transiently decreased and reached its minimum value in 15.0 +/- 3.8 and 10.1 +/- 1.3 s in the trained and untrained subjects, respectively (P < 0.01). CONCLUSION: These data suggest that the vastus lateralis muscle of heavy-resistance strength-trained subjects could have a late activation of the oxidative metabolic system, or greater stored oxygen available, during a very fast, short, isometric maximal contraction.

Functional activity mapping of the mesial hemispheric wall during anticipation of pain.

The relative contributions of autonomic arousal and of cognitive processing to cortical activity during anticipation of pain, and the role of changes in thalamic outflow, are still largely unknown. To address these issues, we investigated with functional magnetic resonance imaging (fMRI) the activity of the contralateral mesial hemispheric wall in 56 healthy volunteers while they expected the stimulation of one foot, which could be either painful or innocuous. The waiting period was characterized by emotional arousal, a moderate rise in heart rate, and by increases in mean fMRI signals in the medial thalamus, mid- and posterior cingulate cortex, and in the putative foot area of the primary somatosensory and motor cortex. The same brain regions, excepting posterior cingulate, were also activated by somatosensory stimulation. We identified by cross-correlation analysis a cluster population whose fMRI signal time course was related to the mean heart rate (HR) profile, showing selective changes of activity during the waiting period. Positively correlated clusters were found mainly in sensorimotor areas, mid- and posterior cingulate, and dorsomedial prefrontal cortex. Negatively correlated clusters predominated in the perigenual anterior cingulate and ventromedial prefrontal cortex. HR clusters had different characteristics from, and showed limited spatial overlap with, clusters whose fMRI signals were related to the psychophysical pain intensity profile; however, both cluster populations were affected by anticipation. These findings unravel a complex pattern of brain activity during uncertain anticipation of noxious input, likely related both to changes in the level of arousal and to cognitive modulation of the pain system.