Heavy-, Severe-, and Extreme-, but not Moderate-Intensity Exercise Increase V̇o2max and Thresholds after 6 Weeks of Training.

INTRODUCTION: This study assessed the effect of individualized, domain-based exercise intensity prescription on changes in maximal oxygen uptake (V̇O2max) and submaximal thresholds. METHODS: Eighty-four young healthy participants (42 Females, 42 Males) were randomly assigned to six age, sex, and V̇O2max-matched groups (14 participants each). Groups performed continuous cycling in the 1) moderate (MOD)-, 2) lower heavy (HVY1)-, and 3) upper heavy-intensity (HVY2)- domain; interval cycling, in the form of 4) high-intensity interval training (HIIT) in the severe-intensity domain, or 5) sprint-interval training (SIT) in the extreme-intensity domain; or no exercise for, 6) control (CON). All training groups except SIT, were work-matched. Training participants completed three sessions per week for six weeks with physiological evaluations performed at PRE, MID and POST intervention. RESULTS: Compared to the change in V̇O2max (∆V̇O2max) in CON (0.1 ± 1.2 mL·kg-1·min-1), all training groups except MOD (1.8 ± 2.7 mL·kg-1·min-1), demonstrated a significant increase (p < 0.05). HIIT produced the highest increase (6.2 ± 2.8 mL·kg-1·min-1) followed by HVY2 (5.4 ± 2.3 mL·kg-1·min-1), SIT (4.7 ± 2.3 mL·kg-1·min-1), and HVY1 (3.3 ± 2.4 mL·kg-1·min-1), respectively. The Δ PO at the estimated lactate threshold (θLT) was similar across HVY1, HVY2, HIIT and SIT which were all greater than CON (p < 0.05). The Δ V̇O2 and Δ PO at θLT for MOD was not different from CON (p > 0.05). HIIT produced the highest Δ PO at maximal metabolic steady state, which was greater than CON, MOD, and SIT (p < 0.05). CONCLUSIONS: This study demonstrated that i) exercise intensity is a key component determining changes in V̇O2max and submaximal thresholds and ii) exercise intensity domain-based prescription allows for a homogenous metabolic stimulus across individuals.

A Ramp versus Step Transition to Constant Work Rate Exercise Decreases Steady-State Oxygen Uptake.

PURPOSE: This study aimed to investigate whether a ramp-to-constant WR (rCWR) transition compared with a square-wave-to-constant WR (CWR) transition within the heavy-intensity domain can reduce metabolic instability and decrease the oxygen cost of exercise. METHODS: Fourteen individuals performed (i) a ramp-incremental test to task failure, (ii) a 21-min CWR within the heavy-intensity domain, and (iii) an rCWR to the same WR. Oxygen uptake (V̇O 2 ), lactate concentration ([La - ]), and muscle oxygen saturation (SmO 2 ) were measured. V̇O 2 and V̇O 2 gain (V̇O 2 -G) during the first 10-min steady-state V̇O 2 were analyzed. [La - ] before, at, and after steady-state V̇O 2 and SmO 2 during the entire 21-min steady-state exercise were also examined. RESULTS: V̇O 2 and V̇O 2 -G during rCWR (2.49 ± 0.58 L·min -1 and 10.7 ± 0.2 mL·min -1 ·W -1 , respectively) were lower ( P < 0.001) than CWR (2.57 ± 0.60 L·min -1 and 11.3 ± 0.2 mL·min -1 ·W -1 , respectively). [La - ] before and at steady-state V̇O 2 during the rCWR condition (1.94 ± 0.60 and 3.52 ± 1.19 mM, respectively) was lower than the CWR condition (3.05 ± 0.82 and 4.15 ± 1.25 mM, respectively) ( P < 0.001). [La - ] dynamics after steady-state V̇O 2 were unstable for the rCWR ( P = 0.011). SmO 2 was unstable within the CWR condition from minutes 4 to 13 ( P < 0.05). CONCLUSIONS: The metabolic disruption caused by the initial minutes of square-wave exercise transitions is a primary contributor to metabolic instability, leading to an increased V̇O 2 -G compared with the rCWR condition approach. The reduced early reliance on anaerobic energy sources during the rCWR condition may be responsible for the lower V̇O 2 -G.

Quantifying Improvement in V˙ o2peak and Exercise Thresholds in Cardiovascular Disease Using Reliable Change Indices.

PURPOSE: Improving aerobic fitness through exercise training is recommended for the treatment of cardiovascular disease (CVD). However, strong justifications for the criteria of assessing improvement in key parameters of aerobic function including estimated lactate threshold (θ LT ), respiratory compensation point (RCP), and peak oxygen uptake (V˙ o2peak ) at the individual level are not established. We applied reliable change index (RCI) statistics to determine minimal meaningful change (MMC RCI ) cutoffs of θ LT , RCP, and V˙ o2peak for individual patients with CVD. METHODS: Sixty-six stable patients post-cardiac event performed three exhaustive treadmill-based incremental exercise tests (modified Bruce) ∼1 wk apart (T1-T3). Breath-by-breath gas exchange and ventilatory variables were measured by metabolic cart and used to identify θ LT , RCP, and V˙ o2peak . Using test-retest reliability and mean difference scores to estimate error and test practice/exposure, respectively, MMC RCI values were calculated for V˙ o2 (mL·min -1. kg -1 ) at θ LT , RCP, and V˙ o2peak . RESULTS: There were no significant between-trial differences in V˙ o2 at θ LT ( P = .78), RCP ( P = .08), or V˙ o2peak ( P = .74) and each variable exhibited excellent test-retest variability (intraclass correlation: 0.97, 0.98, and 0.99; coefficient of variation: 6.5, 5.4, and 4.9% for θ LT , RCP, and V˙ o2peak , respectively). Derived from comparing T1-T2, T1-T3, and T2-T3, the MMC RCI for θ LT were 3.91, 3.56, and 2.64 mL·min -1. kg -1 ; 4.01, 2.80, and 2.79 mL·min -1. kg -1 for RCP; and 3.61, 3.83, and 2.81 mL·min -1. kg -1 for V˙ o2peak . For each variable, MMC RCI scores were lowest for T2-T3 comparisons. CONCLUSION: These MMC RCI scores may be used to establish cutoff criteria for determining meaningful changes for interventions designed to improve aerobic function in individuals with CVD.

The Effects of a 90-km Outdoor Cycling Ride on Performance Outcomes Derived From Ramp-Incremental and 3-Minute All-Out Tests.

ABSTRACT: Bitel, M, Keir, DA, Grossman, K, Barnes, M, Murias, JM, and Belfry, GR. The effects of a 90-km outdoor cycling ride on performance outcomes derived from ramp-incremental and 3-minute all-out tests. J Strength Cond Res 38(3): 540-548, 2024-The purpose of this study was to determine whether laboratory-derived exercise intensity and performance demarcations are altered after prolonged outdoor cycling. Male recreational cyclists ( n = 10; RIDE) performed an exhaustive ramp-incremental test (RAMP) and a 3-minute all-out test (3MT) on a cycle ergometer before and after a 90-km cycling ride. RAMP-derived maximal oxygen uptake (V̇O 2max ), gas exchange threshold (GET), respiratory compensation point (RCP), and associated power output (PO), as well as 3MT-derived critical power (CP) and work performed above CP, were compared before and after ∼3 hours of outdoor cycling. Six active men served as "no-exercise" healthy controls (CON), who, instead, rested for 3 hours between repeated RAMP and 3MT tests. During the 90-km ride, the duration within the moderate-intensity, heavy-intensity, and severe-intensity domains was 59 ± 24%, 40 ± 24%, and 1 ± 1%, respectively. Compared with pre-90 km, post-RAMP exhibited reductions in (a) V̇O 2max (4.04 ± 0.48 vs. 3.80 ± 0.38 L·min -1 ; p = 0.026) and associated PO (392 ± 30 W vs. 357 ± 26 W; p = 0.002); (b) the V̇O 2 and PO at RCP (3.49 ± 0.46 vs. 3.34 ± 0.43 L·min -1 ; p = 0.040 and 312 ± 40 W vs. 292 ± 24 W; p = 0.023); and (c) the PO (214 ± 32 W vs. 198 ± 25 W; p = 0.027), but not the V̇O 2 at GET (2.52 ± 0.44 vs. 2.44 ± 0.38 L·min -1 ; p = 0.388). Pre-90 km vs. post-90 km 3MT variables showed reduced W' (9.8 ± 3.4 vs. 6.8 ± 2.6 kJ; p = 0.002) and unchanged CP (304 ± 26 W and 297 ± 34 W; p = 0.275). In the CON group, there were no differences in V̇O 2max , GET, RCP, W', CP, or associated power outputs ( p > 0.05) pre-to-post 3 hours of rest. The preservation of critical power demonstrates that longer-duration maximal efforts may be sustained after long-duration cycle. However, shorter sprints and higher-intensity efforts eliciting V̇O 2max will exhibit decreased PO after 3 hours of a predominantly moderate-intensity cycle.

Evaluation of the "Step-Ramp-Step" Protocol: Accurate Aerobic Exercise Prescription with Different Steps and Ramp Slopes.

PURPOSE: To assess whether: i) a lower amplitude constant-load MOD is appropriate to determine the mean response time (MRT); ii) the method accurately corrects the dissociation in the V̇O 2 -PO relationship during ramp compared with constant-load exercise when using different ramp slopes. METHODS: Eighteen participants (7 females) performed three SRS tests including: i) step-transitions into MOD from 20 to 50 W (MOD 50 ) and 80 W (MOD 80 ); and ii) slopes of 15, 30, and 45 W·min -1 . The V̇O 2 and PO at the gas exchange threshold (GET) and the corrected respiratory compensation point (RCP CORR ) were determined. Two to three 30-min constant-load trials evaluated the V̇O 2 and PO at the maximal metabolic steady state (MMSS). RESULTS: There were no differences in V̇O 2 at GET (1.97 ± 0.36, 1.99 ± 0.36, 1.95 ± 0.30 L·min -1 ), and RCP (2.81 ± 0.57, 2.86 ± 0.59, 2.84 ± 0.59) between 15, 30, and 45 W·min -1 ramps, respectively ( P > 0.05). The MRT in seconds was not affected by the amplitude of the MOD or the slope of the ramp (range 19 ± 10 s to 23 ± 20 s; P > 0.05). The mean PO at GET was not significantly affected by the amplitude of the MOD or the slope of the ramp (range 130 ± 30 W to 137 ± 30 W; P > 0.05). The PO at RCP CORR was similar for all conditions ((range 186 ± 43 W to 193 ± 47 W; P > 0.05). CONCLUSIONS: The SRS protocol accounts for the V̇O 2 MRT when using smaller amplitude steps, and for the V̇O 2 slow component when using different ramp slopes, allowing for accurate partitioning of the exercise intensity domains in a single test.

The ventilatory response to modified rebreathing is unchanged by hyperoxic severity: implications for the hyperoxic hyperventilation paradox.

Normobaric hyperoxia stimulates ventilation (V̇e) in a time- and dose-dependent manner. Whether this occurs via an oxygen (O2)-specific mechanism or secondary to carbon dioxide (CO2) retention at the central chemoreceptors remains unclear. We measured the ventilatory response to hyperoxic CO2 rebreathing with O2 clamped at increasingly higher pressures. We hypothesized that the V̇e versus Pco2 relationship is fixed and independent of Po2. On four occasions, 20 participants (10 F; mean ± SD age: 24 ± 4 yr) performed three repetitions of modified rebreathing in four, randomized, isoxic-hyperoxic conditions: mild: Po2 = 150 mmHg; moderate: Po2 = 200 mmHg; high: Po2 = 300 mmHg; and extreme: Po2 ≈ 700 mmHg. Breath-by-breath V̇e, end-tidal CO2 ([Formula: see text]), and O2 ([Formula: see text]) were measured by pneumotach and gas analyzer. For each rebreathing trial, the [Formula: see text] at which V̇e rose was identified as the ventilatory recruitment threshold (VRT, mmHg), data before VRT provided baseline V̇e (V̇eBSL, L·min-1) and the slope of the response above VRT gave central chemoreflex sensitivity (V̇eS, L·min-1·mmHg-1). For each condition, VRT, V̇eBSL, and V̇eS from like-trials were averaged, and repeated measures ANOVA assessed between-condition differences. There were no effects of [Formula: see text] on V̇eBSL (mild: 7.4 ± 4.2 L·min-1; moderate: 6.9 ± 4.2 L·min-1; high: 6.5 ± 3.7 L·min-1; extreme: 7.5 ± 2.7 L·min-1; P = 0.24), VRT (mild: 42.8 ± 3.2 mmHg; moderate: 42.5 ± 2.7 mmHg; high: 42.3 ± 2.7 mmHg; extreme: 41.8 ± 2.7 mmHg; P = 0.07), or V̇eS (mild: 4.88 ± 2.6 L·min-1·mmHg-1; moderate: 4.76 ± 2.2 L·min-1·mmHg-1; high: 4.81 ± 2.3 L·min-1·mmHg-1; extreme: 4.39 ± 1.9 L·min-1·mmHg-1; P = 0.41). The V̇e-Pco2 relationship is unaltered across a range of mild to extreme Po2. Brief exposure to normobaric hyperoxia may not independently stimulate breathing nor does it alter central chemoreflex sensitivity.NEW & NOTEWORTHY Normobaric hyperoxia stimulates ventilation (V̇e) in a time- and dose-dependent manner. Whether this occurs directly or indirectly through heightened central carbon dioxide pressure (Pco2) or via central chemoreflex sensitization is unclear. Participants who performed modified rebreathing at high oxygen pressures (Po2) of 150, 200, 300, and ≈700 mmHg exhibited no changes to their ventilatory responses to Pco2. Brief exposure to normobaric hyperoxia may not independently stimulate breathing nor does it alter central chemoreflex sensitivity.

Cardiovascular reflex contributions to sympathetic inhibition during low intensity dynamic leg exercise in healthy middle-age.

Aging augments resting muscle sympathetic nerve activity (MSNA) and sympatho-inhibition during mild dynamic 1-leg exercise. To elucidate which reflexes elicit exercise-induced inhibition, we recruited 19 (9 men) healthy volunteers (mean age 56 ± 9 SD years), assessed their peak oxygen uptake (VO2peak ), and, on another day, measured heart rate (HR), blood pressure (BP) and MSNA (microneurography) at rest and during 1-leg cycling (2 min each at 0 load and 30%-40% VO2peak ), 3 times: (1) seated +2 min of postexercise circulatory occlusion (PECO) (elicit muscle metaboreflex); (2) supine (stimulate cardiopulmonary baroreflexes);and (3) seated, breathing 32% oxygen (suppress peripheral chemoreceptor reflex). While seated, MSNA decreased similarly during mild and moderate exercise (p < 0.001) with no increase during PECO (p = 0.44). Supine posture lowered resting MSNA (main effect p = 0.01) BP and HR. MSNA fell further (p = 0.04) along with diastolic BP and HR during mild, not moderate, supine cycling. Hyperoxia attenuated resting (main effect p = 0.01), but not exercise MSNA. In healthy middle-age, the cardiopulmonary baroreflex and arterial chemoreflex modulate resting MSNA, but contrary to previous observations in young subjects, without counter-regulatory offset by the sympatho-excitatory metaboreflex, resulting in an augmented sympatho-inhibitory response to mild dynamic leg exercise.

A test of the interaction between central and peripheral respiratory chemoreflexes in humans.

How central and peripheral chemoreceptor drives to breathe interact in humans remains contentious. We measured the peripheral chemoreflex sensitivity to hypoxia (PChS) at various isocapnic CO2 tensions ( P C O 2 ${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) to determine the form of the relationship between PChS and central P C O 2 ${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ . Twenty participants (10F) completed three repetitions of modified rebreathing tests with end-tidal P O 2 ${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ ( P ET O 2 ${P_{{\mathrm{ET}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) clamped at 150, 70, 60 and 45 mmHg. End-tidal P C O 2 ${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ( P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ), P ET O 2 ${P_{{\mathrm{ET}}{{\mathrm{O}}_{\mathrm{2}}}}}$ , ventilation ( V ̇ $\dot{V}$ E ) and calculated oxygen saturation (SC O2 ) were measured breath-by-breath by gas-analyser and pneumotach. The V ̇ $\dot{V}$ E - P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ relationship of repeat-trials were linear-interpolated, combined, averaged into 1 mmHg bins, and fitted with a double-linear function ( V ̇ $\dot{V}$ E S, L min-1 mmHg-1 ). PChS was computed at intervals of 1 mmHg of P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ as follows: the difference in V ̇ $\dot{V}$ E between the three hypoxic profiles and the hyperoxic profile (∆ V ̇ $\dot{V}$ E ) was calculated; three ∆ V ̇ $\dot{V}$ E values were plotted against corresponding SC O2 ; and linear regression determined PChS (Lmin-1 mmHg-1 %SC O2 -1 ). These processing steps were repeated at each P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ to produce the PChS vs. isocapnic P C O 2 ${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ relationship. These were fitted with linear and polynomial functions, and Akaike information criterion identified the best-fit model. One-way repeated measures analysis of variance assessed between-condition differences. V ̇ $\dot{V}$ E S increased (P < 0.0001) with isoxic P ET O 2 ${P_{{\mathrm{ET}}{{\mathrm{O}}_{\mathrm{2}}}}}$ from 3.7 ± 1.5 L min-1 mmHg-1 at 150 mmHg to 4.4 ± 1.8, 5.0 ± 1.6 and 6.0 ± 2.2 Lmin-1 mmHg-1 at 70, 60 and 45 mmHg, respectively. Mean SC O2 fell progressively (99.3 ± 0%, 93.7 ± 0.1%, 90.4 ± 0.1% and 80.5 ± 0.1%; P < 0.0001). In all individuals, PChS increased with P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ , and this relationship was best described by a linear model in 75%. Despite increasing central chemoreflex activation, PChS increased linearly with P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ indicative of an additive central-peripheral chemoreflex response. KEY POINTS: How central and peripheral chemoreceptor drives to breathe interact in humans remains contentious. We measured peripheral chemoreflex sensitivity to hypoxia (PChS) at various isocapnic carbon dioxide tensions ( P C O 2 ${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) to determine the form of the relationship between PChS and central P C O 2 ${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ . Participants performed three repetitions of modified rebreathing with end-tidal P O 2 ${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ fixed at 150, 70, 60 and 45 mmHg. PChS was computed at intervals of 1 mmHg of end-tidal P C O 2 ${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ( P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) as follows: the difference in V ̇ $\dot{V}$ E between the three hypoxic profiles and the hyperoxic profile (∆ V ̇ $\dot{V}$ E ) was calculated; three ∆ V ̇ $\dot{V}$ E values were plotted against corresponding calculated oxygen saturation (SC O2 ); and linear regression determined PChS (Lmin-1 mmHg-1 %SC O2 -1 ). In all individuals, PChS increased with P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ , and this relationship was best described by a linear (rather than polynomial) model in 15 of 20. Most participants did not exhibit a hypo- or hyper-additive effect of central chemoreceptors on the peripheral chemoreflex indicating that the interaction was additive.

Do Clinical Exercise Tests Permit Exercise Threshold Identification in Patients Referred to Cardiac Rehabilitation?

BACKGROUND: To evaluate the feasibility of "threshold-based" aerobic exercise prescription in cardiovascular disease, we aimed to quantify the proportion of patients whose clinical cardiopulmonary exercise test (CPET) permit identification of estimated lactate threshold (θLT) and respiratory compensation point (RCP) and to characterize the variability at which these thresholds occur. METHODS: Breath-by-breath CPET data of 1102 patients (65 ± 12 years) referred to cardiac rehabilitation were analyzed to identify peak O2 uptake (V˙O2peak; mL·min-1 and mL·kg-1·min-1) and θLT and RCP (reported as V˙O2, %V˙O2peak, and %peak heart rate [%HRpeak]). Patients were grouped by the presence or absence of thresholds: group 0: neither θLT nor RCP; group 1: θLT only; and group 2: both θLT and RCP. RESULTS: Mean V˙O2peak was 1523 ± 627 mL·min-1 (range: 315-3789 mL·min-1) or 18.0 ± 6.5 mL·kg-1·min-1 (5.2-46.5 mL·kg-1·min-1) and HRpeak was 123 ± 24 beats per minute (bpm) (52 bpm-207 bpm). There were 556 patients (50%) in group 0, 196 (18%) in group 1, and 350 (32%) in group 2. In group 1, mean θLT was 1240 ± 410 mL·min-1 (580-2560 mL·min-1), 75% ± 8%V˙O2peak (52%-92%V˙O2peak), or 84% ± 6%HRpeak (64%-96%HRpeak). In group 2, θLT was 1390 ± 360 mL·min-1 (640-2430 mL·min-1), 70% ± 8%V˙O2peak (41%-88%V˙O2peak), or 78% ± 7%HRpeak (52%-96%HRpeak), and RCP was 1680 ± 440 mL·min-1 (730-3090 mL·min-1), 84% ± 7%V˙O2peak (54%-99%V˙O2peak), or 87% ± 6%HRpeak (59%-99%HRpeak). Compared with group 1, θLT in group 2 occurred at a higher V˙O2 but lower %V˙O2peak and %HRpeak (P < 0.05). CONCLUSIONS: Only 32% of CPETs exhibited both θLT and RCP despite flexibility in protocol options. Commonly used step-based protocols are suboptimal for "threshold-based" exercise prescription.

A Single Test Protocol to Establish the Full Spectrum of Exercise Intensity Prescription.

PURPOSE: We aimed to test the extended capabilities of the SRS protocol by validating its capacity to predict the power outputs for targeted metabolic rates (V̇O 2 ) and time-to-task failure ( Tlim ) within the heavy- and severe-intensity domain, respectively. METHODS: Fourteen young individuals completed (i) an SRS protocol from which the power outputs at GET and RCP (RCP CORR ), and the work accruable above RCP CORR , defined as W ' RAMP , were derived; (ii) one heavy-intensity bout at a power output predicted to elicit a targeted V̇O 2 equidistant from GET and RCP; and (iii) four severe-intensity trials at power outputs predicted to elicit targeted Tlim at minutes 2.5, 5, 10, and 13. These severe-intensity trials were also used to compute the constant-load-derived critical power and W ´ ( W ' CONSTANT ). RESULTS: Targeted (2.41 ± 0.52 L·min -1 ) and measured (2.43 ± 0.52 L·min -1 ) V̇O 2 at the identified heavy-intensity power output (162 ± 43 W) were not different ( P = 0.71) and substantially concordant (CCC = 0.95). Likewise, targeted and measured Tlim for the four identified severe-intensity power outputs were not different ( P > 0.05), and the aggregated coefficient of variation was 10.7% ± 8.9%. The derived power outputs at RCP CORR (192 ± 53 W) and critical power (193 ± 53 W) were not different ( P = 0.65) and highly concordant (CCC = 0.99). There were also no differences between W ' RAMP and W ' CONSTANT ( P = 0.51). CONCLUSIONS: The SRS protocol can accurately predict power outputs to elicit discrete metabolic rates and exercise durations, thus providing, with time efficiency, a high precision for the control of the metabolic stimulus during exercise.

The effect of increasing work rate amplitudes from a common metabolic baseline on the kinetic response of V̇o2p, blood flow, and muscle deoxygenation.

A step-transition in external work rate (WR) increases pulmonary O2 uptake (V̇o2p) in a monoexponential fashion. Although the rate of this increase, quantified by the time constant (τ), has frequently been shown to be similar between multiple different WR amplitudes (ΔWR), the adjustment of O2 delivery to the muscle (via blood flow; BF), a potential regulator of V̇o2p kinetics, has not been extensively studied. To investigate the role of BF on V̇o2p kinetics, 10 participants performed step-transitions on a knee-extension ergometer from a common baseline WR (3 W) to: 24, 33, 45, 54, and 66 W. Each transition lasted 8 min and was repeated four to six times. Volume turbinometry and mass spectrometry, Doppler ultrasound, and near-infrared spectroscopy were used to measure V̇o2p, BF, and muscle deoxygenation (deoxy[Hb + Mb]), respectively. Similar transitions were ensemble-averaged, and phase II V̇o2p, BF, and deoxy[Hb + Mb] were fit with a monoexponential nonlinear least squares regression equation. With increasing ΔWR, τV̇o2p became larger at the higher ΔWRs (P < 0.05), while τBF did not change significantly, and the mean response time (MRT) of deoxy[Hb + Mb] became smaller. These findings that V̇o2p kinetics become slower with increasing ΔWR, while BF kinetics are not influenced by ΔWR, suggest that O2 delivery could not limit V̇o2p in this situation. However, the speeding of deoxy[Hb + Mb] kinetics with increasing ΔWR does imply that the O2 delivery-to-O2 utilization of the microvasculature decreases at higher ΔWRs. This suggests that the contribution of O2 delivery and O2 extraction to V̇O2 in the muscle changes with increasing ΔWR.NEW & NOTEWORTHY A step increase in work rate produces a monoexponential increase in V̇o2p and blood flow to a new steady-state. We found that step transitions from a common metabolic baseline to increasing work rate amplitudes produced a slowing of V̇o2p kinetics, no change in blood flow kinetics, and a speeding of muscle deoxygenation kinetics. As work rate amplitude increased, the ratio of blood flow to V̇o2p became smaller, while the amplitude of muscle deoxygenation became greater. The gain in vascular conductance became smaller, while kinetics tended to become slower at higher work rate amplitudes.

An undergraduate laboratory to study exercise thresholds.

In exercise physiology, laboratory components help students connect theoretical concepts to their own exercise experiences and introduce them to data collection, analysis, and interpretation using classic techniques. Most courses include a lab protocol that involves exhaustive incremental exercise during which expired gas volumes and concentrations of oxygen and carbon dioxide are measured. During these protocols, there are characteristic alterations in gas exchange and ventilatory profiles that give rise to two exercise thresholds: the gas exchange threshold (GET) and the respiratory compensation point (RCP). The ability to explain why these thresholds occur and how they are identified is fundamental to learning in exercise physiology and requisite to the understanding of core concepts including exercise intensity, prescription, and performance. Proper identification of GET and RCP requires the assembly of eight data plots. In the past, the burden of time and expertise required to process and prepare data for interpretation has been a source of frustration. In addition, students often express a desire for more opportunities to practice/refine their skills. The objective of this article is to share a blended laboratory model that features the "Exercise Thresholds App," a free online resource that eliminates postprocessing of data and provides a bank of profiles on which end-users can practice threshold identification skills with immediate feedback. In addition to including prelaboratory and postlaboratory recommendations, we present student accounts of understanding, engagement, and satisfaction following completion of the laboratory experience and introduce a new quiz feature of the app to assist instructors with evaluating student learning.NEW & NOTEWORTHY We present a laboratory to study exercise thresholds from gas exchange and ventilatory measures that features the "Exercise Thresholds App," a free online resource that eliminates postprocessing of data and provides a bank of profiles on which end-users can practice threshold identification skills. In addition to including prelaboratory and postlaboratory recommendations, we present student accounts of understanding, engagement, and satisfaction and introduce a new quiz feature of the app to assist instructors with evaluating learning.

Coupling of [Formula: see text] and [Formula: see text] kinetics: insights from multiple exercise transitions below the estimated lactate threshold.

During a step-change in exercise power output (PO), ventilation ([Formula: see text]) increases with a similar time course to the rate of carbon dioxide delivery to the lungs ([Formula: see text]). To test the strength of this coupling, we compared [Formula: see text] and [Formula: see text] kinetics from ten independent exercise transitions performed within the moderate-intensity domain. Thirteen males completed 3-5 repetitions of ∆40 W step transitions initiated from 20, 40, 60, 80, 100, and 120 W on a cycle ergometer. Preceding the ∆40 W step transitions from 60, 80, 100, and 120 W was a 6 min bout of 20 W cycling from which the transitions of variable ∆PO were examined. Gas exchange ([Formula: see text] and oxygen uptake, [Formula: see text]) and [Formula: see text] were measured by mass spectrometry and volume turbine. The kinetics of the responses were characterized by the time constant (τ) and amplitude (Δ[Formula: see text]/Δ[Formula: see text]). Overall, [Formula: see text] kinetics were consistently slower than [Formula: see text] kinetics (by ~ 45%) and τ[Formula: see text] rose progressively with increasing baseline PO and with heightened ∆PO from a common baseline. Compared to τ[Formula: see text], τ[Formula: see text] was on average slightly greater (by ~ 4 s). Repeated-measures analysis of variance revealed that there was no interaction between τ[Formula: see text] and τ[Formula: see text] in either the variable baseline (p = 0.49) and constant baseline (p = 0.56) conditions indicating that each changed in unison. Additionally, for Δ[Formula: see text]/Δ[Formula: see text], there was no effect of either variable baseline PO (p = 0.05) or increasing ΔPO (p = 0.16). These data provide further evidence that, within the moderate-intensity domain, both the temporal- and amplitude-based characteristics of V̇E kinetics are inextricably linked to those of [Formula: see text].

Normal and excessive muscle sympathetic nerve activity in heart failure: implications for future trials of therapeutic autonomic modulation.

AIMS: Patients with sympathetic excess are those most likely to benefit from novel interventions targeting the autonomic nervous system. To inform such personalized therapy, we identified determinants of augmented muscle sympathetic nerve activity (MSNA) in heart failure, versus healthy controls. METHODS AND RESULTS: We compared data acquired in 177 conventionally-treated, stable non-diabetic patients in sinus rhythm, aged 18-79 years (149 males; 28 females; left ventricular ejection fraction [LVEF] 25 ± 11% [mean ± standard deviation]; range 5-60%), and, concurrently, under similar conditions, in 658 healthy, normotensive volunteers (398 males; aged 18-81 years). In heart failure, MSNA ranged between 7 and 90 bursts·min-1 , proportionate to heart rate (p < 0.0001) and body mass index (BMI) (p = 0.03), but was unrelated to age, blood pressure, or drug therapy. Mean MSNA, adjusted for age, sex, BMI, and heart rate, was greater in heart failure (+14.2 bursts·min-1 ; 95% confidence interval [CI] 12.1-16.3; p < 0.0001), but lower in women (-5.0 bursts·min-1 ; 95% CI 3.4-6.6; p < 0.0001). With spline modeling, LVEF accounted for 9.8% of MSNA variance; MSNA related inversely to LVEF below an inflection point of ∼21% (p < 0.006), but not above. Burst incidence was greater in ischaemic than dilated cardiomyopathy (p = 0.01), and patients with sleep apnoea (p = 0.03). Burst frequency correlated inversely with stroke volume (p < 0.001), cardiac output (p < 0.001), and peak oxygen consumption (p = 0.002), and directly with norepinephrine (p < 0.0001) and peripheral resistance (p < 0.001). CONCLUSION: Burst frequency and incidence exceeded normative values in only ∼53% and ∼33% of patients. Such diversity encourages selective deployment of sympatho-modulatory therapies. Clinical characteristics can highlight individuals who may benefit from future personalized interventions targeting pathological sympathetic activation.

Influence of sex and age on the relationship between aerobic fitness and muscle sympathetic nerve activity in healthy adults.

We examined the influence of sex and age on the relationship between aerobic fitness and muscle sympathetic nerve activity (MSNA) in healthy adults. Data were assessed from 224 volunteers (88 females), aged 18-76 yr, in whom resting MSNA (microneurography) and peak oxygen uptake (V̇o2peak; incremental exercise test) were evaluated. When separated into younger (<50 yr) and older (≥50 yr) subgroups, there were inverse relationships between relative V̇o2peak (mL·kg-1·min-1) and MSNA burst frequency in younger males (R2 = 0.21, P < 0.0001) and older females (R2 = 0.36, P < 0.01), but not older males (R2 = 0.05, P = 0.08) or younger females (R2 = 0.03, P = 0.14). Similar patterns were observed with absolute V̇o2peak (L·min-1) and percent-predicted (based on age, sex, weight, height, and modality), and with burst incidence. Sex and age influence the relationship between aerobic fitness and resting MSNA, and, thus, must be considered as key variables when studying these potential associations; inverse relationships are strongest in younger males and older females.NEW & NOTEWORTHY Our data reveal for the first time that associations between aerobic fitness and resting muscle sympathetic nerve activity are sex and age specific; inverse relationships are evident in younger males (<50 yr) and older females (≥50 yr), but absent in younger females (<50 yr) and older males (≥50 yr).

Strategies to improve respiratory chemoreflex characterization by Duffin's rebreathing.

NEW FINDINGS: What is the central question of this study? We assessed the test-retest variability of respiratory chemoreflex characterization by Duffin's modified rebreathing method and explored whether signal averaging of repeated trials improves confidence in parameter estimation. What is the main finding and its importance? Modified rebreathing is a reproducible method to characterize responses of central and peripheral respiratory chemoreflexes. Signal averaging of multiple repeated tests minimizes within- and between-test variability, improves the confidence of chemoreflex characterization and reduces the minimal change in parameters required to establish an effect. Future experiments that apply this method might benefit from signal averaging to improve its discriminatory effect. ABSTRACT: We assessed the test-retest variability of central and peripheral respiratory chemoreflex characterization by Duffin's modified rebreathing method and explored whether signal averaging of repeated trials improves confidence in parameter estimation. Over four laboratory visits, 13 participants (mean ± SD age, 25 ± 5 years) performed six repetitions of modified rebreathing in isoxic-hypoxic conditions [end-tidal P O 2 ${P_{{{\rm{O}}_{\rm{2}}}}}$ ( P ET , O 2 ${P_{{\rm{ET,}}{{\rm{O}}_{\rm{2}}}}}$ )  = 50 mmHg] and isoxic-hyperoxic conditions ( P ET , O 2 ${P_{{\rm{ET,}}{{\rm{O}}_{\rm{2}}}}}$   = 150 mmHg). End-tidal P C O 2 ${P_{{\rm{C}}{{\rm{O}}_{\rm{2}}}}}$ ( P ET , C O 2 ${P_{{\rm{ET,C}}{{\rm{O}}_{\rm{2}}}}}$ ), P ET , O 2 ${P_{{\rm{ET,}}{{\rm{O}}_{\rm{2}}}}}$ and minute ventilation ( V ̇ $\dot {\rm V}$ E ) were measured breath-by-breath, by gas analyser and pneumotachograph. The V ̇ $\dot {\rm V}$ E versus P ET , C O 2 ${P_{{\rm{ET,C}}{{\rm{O}}_{\rm{2}}}}}$ relationships were fitted with a piecewise model to estimate the ventilatory recruitment threshold (VRT) and the slope above the VRT ( V ̇ $\dot {\rm V}$ E S). Breath-by-breath data from the three within- and between-day trials were averaged using two approaches [simple average (fit then average) and ensemble average (average then fit)] and compared with a single-trial fit. Variability was assessed by intraclass correlation (ICC) and coefficient of variance (CV), and the minimal detectable change was computed for each approach using two independent sets of three trials. Within days, the VRT and V ̇ $\dot {\rm V}$ E S exhibited excellent test-retest variability in both hyperoxic conditions (VRT: ICC = 0.965, CV = 2.3%; V ̇ $\dot {\rm V}$ E S: ICC = 0.932, CV = 15.5%) and hypoxic conditions (VRT: ICC = 0.970, CV = 2.9%; V ̇ $\dot {\rm V}$ E S: ICC = 0.891, CV = 17.2%). Between-day reproducibility was also excellent (hyperoxia, VRT: ICC = 0.930, CV = 2.2%; V ̇ $\dot {\rm V}$ E S: ICC = 0.918, CV = 14.2%; and hypoxia, VRT: ICC = 0.940, CV = 3.0%; V ̇ $\dot {\rm V}$ E S: ICC = 0.880, CV = 18.1%). Compared with a single-trial fit, there were no differences in VRT or V ̇ $\dot {\rm V}$ E S using the simple average or ensemble average approaches; however, ensemble averaging reduced the minimal detectable change for V ̇ $\dot {\rm V}$ E S from 2.95 to 1.39 L min-1  mmHg-1 (hyperoxia) and from 3.64 to 1.82 L min-1  mmHg-1 (hypoxia). Single trials of modified rebreathing are reproducible; however, signal averaging of repeated trials improves confidence in parameter estimation.

The effects of exercise intensity and duration on the relationship between the slow component of V̇O2 and peripheral fatigue.

AIM: If the development of the oxygen uptake slow component (V̇O2SC ) and muscle fatigue are related, these variables should remain coupled in a time- and intensity-dependent manner. METHODS: 16 participants (7 females) visited the laboratory on 7 separate occasions: (1) three 6-minutes moderate-intensity cycling exercise bouts proceeded by a ramp incremental test; (2-3) 30-minutes constant power output (PO) exercise bout to determine the maximal lactate steady state (MLSS); (4-7) constant-PO exercise bouts to task failure (TTF), pseudorandomized order, at (i) 15% below the PO at MLSS; (ii) 10 W below MLSS; (iii) MLSS; (iv) 10 W above MLSS (first intensity and randomized order thereafter). Neuromuscular fatigue was characterized by isometric maximal voluntary contractions and femoral nerve electrical stimulation of knee extensors to measure peripheral fatigue at baseline, at min 5, 10, 20, 30 and TTF. Pulmonary oxygen uptake (V̇O2 ) was continuously recorded during the constant-PO bouts and V̇O2SC was characterized based on each individual V̇O2 kinetics during moderate transitions. RESULTS: The development of V̇O2SC and peripheral fatigue were correlated across time (r2 adj range of 0.64-0.80) and amongst each exercise intensity (r2 adj range of 0.26-0.30) (all P < .001). Also, TTF was correlated with V̇O2SC and neuromuscular fatigue parameters (r2 adj range of 0.52-0.82, all P < .001). CONCLUSION: The V̇O2SC and peripheral fatigue development are correlated throughout the exercise in a time- and intensity-dependent manner, suggesting that the V̇O2SC may depend on muscle fatigue even if the mechanisms of reduced contractile function are different amongst intensities.