The intramuscular contribution to the slow oxygen uptake kinetics during exercise in chronic heart failure is related to the severity of the condition

The mechanism for slow pulmonary O(2) uptake (Vo(2)) kinetics in patients with chronic heart failure (CHF) is unclear but may be due to limitations in the intramuscular control of O(2) utilization or O(2) delivery. Recent evidence of a transient overshoot in microvascular deoxygenation supports the latter. Prior (or warm-up) exercise can increase O(2) delivery in healthy individuals. We therefore aimed to determine whether prior exercise could increase muscle oxygenation and speed Vo(2) kinetics during exercise in CHF. Fifteen men with CHF (New York Heart Association I-III) due to left ventricular systolic dysfunction performed two 6-min moderate-intensity exercise transitions (bouts 1 and 2, separated by 6 min of rest) from rest to 90% of lactate threshold on a cycle ergometer. Vo(2) was measured using a turbine and a mass spectrometer, and muscle tissue oxygenation index (TOI) was determined by near-infrared spectroscopy. Prior exercise increased resting TOI by 5.3 ± 2.4% (P = 0.001), attenuated the deoxygenation overshoot (-3.9 ± 3.6 vs. -2.0 ± 1.4%, P = 0.011), and speeded the Vo(2) time constant (τVo(2); 49 ± 19 vs. 41 ± 16 s, P = 0.003). Resting TOI was correlated to τVo(2) before (R(2) = 0.51, P = 0.014) and after (R(2) = 0.36, P = 0.051) warm-up exercise. However, the mean response time of TOI was speeded between bouts in half of the patients (26 ± 8 vs. 20 ± 8 s) and slowed in the remainder (32 ± 11 vs. 44 ± 16 s), the latter group having worse New York Heart Association scores (P = 0.042) and slower Vo(2) kinetics (P = 0.001). These data indicate that prior moderate-intensity exercise improves muscle oxygenation and speeds Vo(2) kinetics in CHF. The most severely limited patients, however, appear to have an intramuscular pathology that limits Vo(2) kinetics during moderate exercise.     

Oxygen uptake kinetics during two bouts of heavy cycling separated by fatiguing sprint exercise in humans.

We tested the hypothesis that O(2) uptake (Vo(2)) kinetics at the onset of heavy exercise would be altered in a state of muscle fatigue and prior metabolic acidosis. Eight well-trained cyclists completed two identical bouts of 6-min cycling exercise at >85% of peak Vo(2) separated by three successive bouts of 30 s of sprint cycling. Not only was baseline Vo(2) elevated after prior sprint exercises but also the time constant of phase II Vo(2) kinetics was faster (28.9 +/- 2.4 vs. 22.2 +/- 1.7 s; P < 0.05). CO(2) output (Vco(2)) was significantly reduced throughout the second exercise bout. Subsequently Vo(2) was greater at 3 min and increased less after this after prior sprint exercise. Cardiac output, estimated by impedance cardiography, was significantly higher in the first 2 min of the second heavy exercise bout. Normalized integrated surface electromyography of four leg muscles and normalized mean power frequency were not different between exercise bouts. Vo(2) and Vco(2) kinetic responses to heavy exercise were markedly altered by prior multiple sprint exercises.     

Morning-to-evening differences in oxygen uptake kinetics in short-duration cycling exercise

This study analyzed diurnal variations in oxygen (O(2)) uptake kinetics and efficiency during a moderate cycle ergometer exercise. Fourteen physically active diurnally active male subjects (age 23+/-5 yrs) not specifically trained at cycling first completed a test to determine their ventilatory threshold (T(vent)) and maximal oxygen consumption (VO(2max)); one week later, they completed four bouts of testing in the morning and evening in a random order, each separated by at least 24 h. For each period of the day (07:00-08:30 h and 19:00-20:30 h), subjects performed two bouts. Each bout was composed of a 5 min cycling exercise at 45 W, followed after 5 min rest by a 10 min cycling exercise at 80% of the power output associated with T(vent). Gas exchanges were analyzed breath-by-breath and fitted using a mono-exponential function. During moderate exercise, the time constant and amplitude of VO(2) kinetics were significantly higher in the morning compared to the evening. The net efficiency increased from the morning to evening (17.3+/-4 vs. 20.5+/-2%; p<0.05), and the variability of cycling cadence was greater during the morning than evening (+34%; p<0.05). These findings suggest that VO(2) responses are affected by the time of day and could be related to variability in muscle activity pattern.     

Speeding of VO2 kinetics during moderate-intensity exercise subsequent to heavy-intensity exercise is associated with improved local O2 distribution

The relationship between the adjustment of muscle deoxygenation (Δ[HHb]) and phase II V(O(2p)) during moderate-intensity exercise was examined before (Mod 1) and after (Mod 2) a bout of heavy-intensity "priming" exercise. Moderate intensity V(O(2p)) and Δ[HHb] kinetics were determined in 18 young males (26 ± 3 yr). V(O(2p)) was measured breath-by-breath. Changes in Δ[HHb] of the vastus lateralis muscle were measured by near-infrared spectroscopy. V(O(2p)) and Δ[HHb] response profiles were fit using a monoexponential model, and scaled to a relative % of the response (0-100%). The Δ[HHb]/Vo(2) ratio for each individual (reflecting the local matching of O(2) delivery to O(2) utilization) was calculated as the average Δ[HHb]/Vo(2) response from 20 s to 120 s during the exercise on-transient. Phase II τV(O(2p)) was reduced in Mod 2 compared with Mod 1 (P < 0.05). The effective τ'Δ[HHb] remained the same in Mod 1 and Mod 2 (P > 0.05). During Mod 1, there was an "overshoot" in the Δ[HHb]/Vo(2) ratio (1.08; P < 0.05) that was not present during Mod 2 (1.01; P > 0.05). There was a positive correlation between the reduction in the Δ[HHb]/Vo(2) ratio and the smaller τV(O(2p)) from Mod 1 to Mod 2 (r = 0.78; P < 0.05). This study showed that a smaller τV(O(2p)) during a moderate bout of exercise subsequent to a heavy-intensity priming exercise was associated with improved microvascular O(2) delivery during the on-transient of exercise, as suggested by a smaller Δ[HHb]/Vo(2) ratio.     

Effects of prior heavy exercise on phase II pulmonary oxygen uptake kinetics during heavy exercise.

We tested the hypothesis that heavy-exercise phase II oxygen uptake (VO(2)) kinetics could be speeded by prior heavy exercise. Ten subjects performed four protocols involving 6-min exercise bouts on a cycle ergometer separated by 6 min of recovery: 1) moderate followed by moderate exercise; 2) moderate followed by heavy exercise; 3) heavy followed by moderate exercise; and 4) heavy followed by heavy exercise. The VO(2) responses were modeled using two (moderate exercise) or three (heavy exercise) independent exponential terms. Neither moderate- nor heavy-intensity exercise had an effect on the VO(2) kinetic response to subsequent moderate exercise. Although heavy-intensity exercise significantly reduced the mean response time in the second heavy exercise bout (from 65.2 +/- 4.1 to 47.0 +/- 3.1 s; P < 0.05), it had no significant effect on either the amplitude or the time constant (from 23.9 +/- 1.9 to 25.3 +/- 2.9 s) of the VO(2) response in phase II. Instead, this "speeding" was due to a significant reduction in the amplitude of the VO(2) slow component. These results suggest phase II VO(2) kinetics are not speeded by prior heavy exercise.     

Similar level of impairment in exercise performance and oxygen uptake kinetics in middle-aged men and women with type 2 diabetes

The present study tested the hypothesis that the magnitude of the type 2 diabetes-induced impairments in peak oxygen uptake (Vo(2)) and Vo(2) kinetics would be greater in females than males in middle-aged participants. Thirty-two individuals with type 2 diabetes (16 male, 16 female), and 32 age- and body mass index (BMI)-matched healthy individuals (16 male, 16 female) were recruited. Initially, the ventilatory threshold (VT) and peak Vo(2) were determined. On a separate day, subjects completed four 6-min bouts of constant-load cycling at 80% VT for the determination of Vo(2) kinetics using standard procedures. Cardiac output (CO) (inert gas rebreathing) was recorded at rest, 30, and 240 s during two additional bouts. Peak Vo(2) (ml·kg(-1)·min(-1)) was significantly reduced in men and women with type 2 diabetes compared with their respective nondiabetic counterparts (men, 27.8 ± 4.4 vs. 31.1 ± 6.2 ml·kg(-1)·min(-1); women, 19.4 ± 4.1 vs. 21.4 ± 2.9 ml·kg(-1)·min(-1)). The time constant (s) of phase 2 (τ(2)) and mean response time (s) of the Vo(2) response (MRT) were slowed in women with type 2 diabetes compared with healthy women (τ(2), 43.3 ± 9.8 vs. 33.6 ± 10.0 s; MRT, 51.7 ± 9.4 vs. 43.5 ± 11.4s) and in men with type 2 diabetes compared with nondiabetic men (τ(2), 43.8 ± 12.0 vs. 35.3 ± 9.5 s; MRT, 57.6 ± 8.3 vs. 47.3 ± 9.3 s). The magnitude of these impairments was not different between males and females. The steady-state CO responses or the dynamic responses of CO were not affected by type 2 diabetes among men or women. The results suggest that the type 2 diabetes-induced impairments in peak Vo(2) and Vo(2) kinetics are not affected by sex in middle aged participants.     

Excessive oxygen uptake during exercise and recovery in heavy exercise

The aim of this study was to determine whether excessive oxygen uptake (Vo2) occurs not only during exercise but also during recovery after heavy exercise. After previous exercise at zero watts for 4 min, the main exercise was performed for 10 min. Then recovery exercise at zero watts was performed for 10 min. The main exercises were moderate and heavy exercises at exercise intensities of 40 % and 70 % of peak Vo2, respectively. Vo2 kinetics above zero watts was obtained by subtracting Vo2 at zero watts of previous exercise (DeltaVo2). Delta Vo2 in moderate exercise was multiplied by the ratio of power output performed in moderate and heavy exercises so as to estimate the Delta Vo2 applicable to heavy exercise. The difference between Delta Vo2 in heavy exercise and Delta Vo2 estimated from the value of moderate exercise was obtained. The obtained Vo2 was defined as excessive Vo2. The time constant of excessive Vo2 during exercise (1.88+/-0.70 min) was significantly shorter than that during recovery (9.61+/-6.92 min). Thus, there was excessive Vo2 during recovery from heavy exercise, suggesting that O2/ATP ratio becomes high after a time delay in heavy exercise and the high ratio continues until recovery.     

Effects of prior heavy-intensity exercise during single-leg knee extension on VO2 kinetics and limb blood flow.

The effects of prior heavy-intensity exercise on O(2) uptake (Vo(2)) kinetics of a second heavy exercise may be due to vasodilation (associated with metabolic acidosis) and improved muscle blood flow. This study examined the effect of prior heavy-intensity exercise on femoral artery blood flow (Qleg) and its relationship with Vo(2) kinetics. Five young subjects completed five to eight repeats of two 6-min bouts of heavy-intensity one-legged, knee-extension exercise separated by 6 min of loadless exercise. Vo(2) was measured breath by breath. Pulsed-wave Doppler ultrasound was used to measure Qleg. Vo(2) and blood flow velocity data were fit using a monoexponential model to identify phase II and phase III time periods and estimate the response amplitudes and time constants (tau). Phase II Vo(2) kinetics was speeded on the second heavy-intensity exercise [mean tau (SD), 29 (10) s to 24 (10) s, P < 0.05] with no change in the phase II (or phase III) amplitude. Qleg was elevated before the second exercise [1.55 (0.34) l/min to 1.90 (0.25) l/min, P < 0.05], but the amplitude and time course [tau, 25 (13) s to 35 (13) s] were not changed, such that throughout the transient the Qleg (and DeltaQleg/DeltaVo(2)) did not differ from the prior heavy exercise. Thus Vo(2) kinetics were accelerated on the second exercise, but the faster kinetics were not associated with changes in Qleg. Thus limb blood flow appears not to limit Vo(2) kinetics during single-leg heavy-intensity exercise nor to be the mechanism of the altered Vo(2) response after heavy-intensity prior exercise.     

Facial cooling-induced bradycardia does not slow pulmonary V.O2 kinetics at the onset of high-intensity exercise.

The mechanism(s) underlying the attenuation of the slow component of pulmonary O2 uptake (Vo2) by prior heavy-intensity exercise is (are) poorly understood but may be ascribed to either an intramuscular-metabolic or a circulatory modification resulting from "priming" exercise. We investigated the effects of altering the circulatory dynamics by delayed vagal withdrawal to the circulation induced by the cold face stimulation (CFS) on the Vo2 kinetics during repeated bouts of heavy-intensity cycling exercise. Five healthy subjects (aged 21-43 yr) volunteered to participate in this study and initially performed two consecutive 6-min leg cycling exercise bouts (work rate: 50% of the difference between lactate threshold and maximal Vo2) separated by 6-min baseline rest without CFS as a control (N1 and N2). CFS was then applied separately, by gel-filled cold compresses to the face for 2-min spanning the rest-exercise transition, to each of the first bout (CFS1) or second bout (CFS2) of repeated heavy-intensity exercise. In the control protocol, Vo2 responses in N2 showed a facilitated adaptation compared with those in N1, mainly attributable to the reduction of slow component. CFS application successfully slowed and delayed the heart rate (HR) kinetics (P < 0.05) on transition to exercise [HR time constant; N1: 55.6 +/- 16.0 (SD) vs. CFS1: 69.0 +/- 12.8 s and N2: 55.5 +/- 11.8 vs. CFS2: 64.0 +/- 17.5 s]; however, it did not affect the "primary" Vo2 kinetics [Vo2 time constant; N1: 23.7 +/- 7.9 (SD) vs. CFS1: 20.9 +/- 3.8 s, and N2: 23.3 +/- 10.3 vs. CFS2: 17.4 +/- 6.3 s]. In conclusion, increased vagal withdrawal delayed and slowed the circulatory response but did not alter the Vo2 kinetics at the onset of supra-lactate threshold cycling exercise. As the facilitation of Vo2 subsequent to prior heavy leg cycling exercise is not attenuated by slowing the central circulation, it seems unlikely that this facilitation is exclusively determined by a blood flow-related mechanism.     

Pulmonary O2 uptake kinetics as a determinant of high-intensity exercise tolerance in humans

Tolerance to high-intensity constant-power (P) exercise is well described by a hyperbola with two parameters: a curvature constant (W') and power asymptote termed "critical power" (CP). Since the ability to sustain exercise is closely related to the ability to meet the ATP demand in a steady state, we reasoned that pulmonary O(2) uptake (Vo(2)) kinetics would relate to the P-tolerable duration (t(lim)) parameters. We hypothesized that 1) the fundamental time constant (τVo(2)) would relate inversely to CP; and 2) the slow-component magnitude (ΔVo(2sc)) would relate directly to W'. Fourteen healthy men performed cycle ergometry protocols to the limit of tolerance: 1) an incremental ramp test; 2) a series of constant-P tests to determine Vo(2max), CP, and W'; and 3) repeated constant-P tests (WR(6)) normalized to a 6 min t(lim) for τVo(2) and ΔVo(2sc) estimation. The WR(6) t(lim) averaged 365 ± 16 s, and Vo(2max) (4.18 ± 0.49 l/min) was achieved in every case. CP (range: 171-294 W) was inversely correlated with τVo(2) (18-38 s; R(2) = 0.90), and W' (12.8-29.9 kJ) was directly correlated with ΔVo(2sc) (0.42-0.96 l/min; R(2) = 0.76). These findings support the notions that 1) rapid Vo(2) adaptation at exercise onset allows a steady state to be achieved at higher work rates compared with when Vo(2) kinetics are slower; and 2) exercise exceeding this limit initiates a "fatigue cascade" linking W' to a progressive increase in the O(2) cost of power production (Vo(2sc)), which, if continued, results in attainment of Vo(2max) and exercise intolerance. Collectively, these data implicate Vo(2) kinetics as a key determinant of high-intensity exercise tolerance in humans.     

Morning‐to‐Evening Differences in Oxygen Uptake Kinetics in Short‐Duration Cycling Exercise

This study analyzed diurnal variations in oxygen (O₂) uptake kinetics and efficiency during a moderate cycle ergometer exercise. Fourteen physically active diurnally active male subjects (age 23±5 yrs) not specifically trained at cycling first completed a test to determine their ventilatory threshold (T_vent) and maximal oxygen consumption (VO_2max); one week later, they completed four bouts of testing in the morning and evening in a random order, each separated by at least 24 h. For each period of the day (07:00–08:30 h and 19:00–20:30 h), subjects performed two bouts. Each bout was composed of a 5 min cycling exercise at 45 W, followed after 5 min rest by a 10 min cycling exercise at 80% of the power output associated with T_vent. Gas exchanges were analyzed breath‐by‐breath and fitted using a mono‐exponential function. During moderate exercise, the time constant and amplitude of VO₂ kinetics were significantly higher in the morning compared to the evening. The net efficiency increased from the morning to evening (17.3±4 vs. 20.5±2%; p<0.05), and the variability of cycling cadence was greater during the morning than evening (+34%; p<0.05). These findings suggest that VO₂ responses are affected by the time of day and could be related to variability in muscle activity pattern.     

Older type 2 diabetic males do not exhibit abnormal pulmonary oxygen uptake and muscle oxygen utilization dynamics during submaximal cycling exercise

There are reports of abnormal pulmonary oxygen uptake (Vo(2)) and deoxygenated hemoglobin ([HHb]) kinetics in individuals with Type 2 diabetes (T2D) below 50 yr of age with disease durations of <5 yr. We examined the Vo(2) and muscle [HHb] kinetics in 12 older T2D patients with extended disease durations (age: 65 ± 5 years; disease duration 9.3 ± 3.8 years) and 12 healthy age-matched control participants (CON; age: 62 ± 6 years). Maximal oxygen uptake (Vo(2max)) was determined via a ramp incremental cycle test and Vo(2) and [HHb] kinetics were determined during subsequent submaximal step exercise. The Vo(2max) was significantly reduced (P < 0.05) in individuals with T2D compared with CON (1.98 ± 0.43 vs. 2.72 ± 0.40 l/min, respectively) but, surprisingly, Vo(2) kinetics was not different in T2D compared with CON (phase II time constant: 43 ± 17 vs. 41 ± 12 s, respectively). The Δ[HHb]/ΔVo(2) was significantly higher in T2D compared with CON (235 ± 99 vs. 135 ± 33 AU·l(-1)·min(-1); P < 0.05). Despite a lower Vo(2max), Vo(2) kinetics is not different in older T2D compared with healthy age-matched control participants. The elevated Δ[HHb]/ΔVo(2) in T2D individuals possibly indicates a compromised muscle blood flow that mandates a greater O(2) extraction during exercise. Longer disease duration may result in adaptations in the O(2) extraction capabilities of individuals with T2D, thereby mitigating the expected age-related slowing of Vo(2) kinetics.     

Effects of "priming" exercise on pulmonary O2 uptake and muscle deoxygenation kinetics during heavy-intensity cycle exercise in the supine and upright positions.

We hypothesized that the performance of prior heavy exercise would speed the phase 2 oxygen consumption (VO2) kinetics during subsequent heavy exercise in the supine position (where perfusion pressure might limit muscle O2 supply) but not in the upright position. Eight healthy men (mean +/- SD age 24 +/- 7 yr; body mass 75.0 +/- 5.8 kg) completed a double-step test protocol involving two bouts of 6 min of heavy cycle exercise, separated by a 10-min recovery period, on two occasions in each of the upright and supine positions. Pulmonary O2 uptake was measured breath by breath and muscle oxygenation was assessed using near-infrared spectroscopy (NIRS). The NIRS data indicated that the performance of prior exercise resulted in hyperemia in both body positions. In the upright position, prior exercise had no significant effect on the time constant tau of the VO2 response in phase 2 (bout 1: 29 +/- 10 vs. bout 2: 28 +/- 4 s; P = 0.91) but reduced the amplitude of the VO2 slow component (bout 1: 0.45 +/- 0.16 vs. bout 2: 0.22 +/- 0.14 l/min; P = 0.006) during subsequent heavy exercise. In contrast, in the supine position, prior exercise resulted in a significant reduction in the phase 2 tau (bout 1: 38 +/- 18 vs. bout 2: 24 +/- 9 s; P = 0.03) but did not alter the amplitude of the VO2 slow component (bout 1: 0.40 +/- 0.29 vs. bout 2: 0.41 +/- 0.20 l/min; P = 0.86). These results suggest that the performance of prior heavy exercise enables a speeding of phase 2 VO2 kinetics during heavy exercise in the supine position, presumably by negating an O2 delivery limitation that was extant in the control condition, but not during upright exercise, where muscle O2 supply was probably not limiting.     

Effects of priming exercise on the speed of adjustment of muscle oxidative metabolism at the onset of moderate-intensity step transitions in older adults

Aging is associated with a functional decline of the oxidative metabolism due to progressive limitations of both O(2) delivery and utilization. Priming exercise (PE) increases the speed of adjustment of oxidative metabolism during successive moderate-intensity transitions. We tested the hypothesis that such improvement is due to a better matching of O(2) delivery to utilization within the working muscles. In 21 healthy older adults (65.7 ± 5 yr), we measured contemporaneously noninvasive indexes of the overall speed of adjustment of the oxidative metabolism (i.e., pulmonary Vo(2) kinetics), of the bulk O(2) delivery (i.e., cardiac output), and of the rate of muscle deoxygenation (i.e., deoxygenated hemoglobin, HHb) during moderate-intensity step transitions, either with (ModB) or without (ModA) prior PE. The local matching of O(2) delivery to utilization was evaluated by the ΔHHb/ΔVo(2) ratio index. The overall speed of adjustment of the Vo(2) kinetics was significantly increased in ModB compared with ModA (P < 0.05). On the contrary, the kinetics of cardiac output was unaffected by PE. At the muscle level, ModB was associated with a significant reduction of the "overshoot" in the ΔHHb/ΔVo(2) ratio compared with ModA (P < 0.05), suggesting an improved O(2) delivery. Our data are compatible with the hypothesis that, in older adults, PE, prior to moderate-intensity exercise, beneficially affects the speed of adjustment of oxidative metabolism due to an acute improvement of the local matching of O(2) delivery to utilization.     

Thigh muscle activation distribution and pulmonary VO2 kinetics during moderate, heavy, and very heavy intensity cycling exercise in humans

The mechanisms underlying the oxygen uptake (Vo(2)) slow component during supra-lactate threshold (supra-LT) exercise are poorly understood. Evidence suggests that the Vo(2) slow component may be caused by progressive muscle recruitment during exercise. We therefore examined whether leg muscle activation patterns [from the transverse relaxation time (T2) of magnetic resonance images] were associated with supra-LT Vo(2) kinetic parameters. Eleven subjects performed 6-min cycle ergometry at moderate (80% LT), heavy (70% between LT and critical power; CP), and very heavy (7% above CP) intensities with breath-by-breath pulmonary Vo(2) measurement. T2 in 10 leg muscles was evaluated at rest and after 3 and 6 min of exercise. During moderate exercise, nine muscles achieved a steady-state T2 by 3 min; only in the vastus medialis did T2 increase further after 6 min. During heavy exercise, T2 in the entire vastus group increased between minutes 3 and 6, and additional increases in T2 were seen in adductor magnus and gracilis during this period of very heavy exercise. The Vo(2) slow component increased with increasing exercise intensity (being functionally zero during moderate exercise). The distribution of T2 was more diverse as supra-LT exercise progressed: T2 variance (ms) increased from 3.6 +/- 0.2 to 6.5 +/- 1.7 between 3 and 6 min of heavy exercise and from 5.5 +/- 0.8 to 12.3 +/- 5.4 in very heavy exercise (rest = 3.1 +/- 0.6). The T2 distribution was significantly correlated with the magnitude of the Vo(2) slow component (P < 0.05). These data are consistent with the notion that the Vo(2) slow component is an expression of progressive muscle recruitment during supra-LT exercise.     

VO(2) kinetics in heavy exercise is not altered by prior exercise with a different muscle group.

We examined whether lactic acidemia-induced hyperemia at the onset of high-intensity leg exercise contributed to the speeding of pulmonary O(2) uptake (VO(2)) after prior heavy exercise of the same muscle group or a different muscle group (i.e., arm). Six healthy male subjects performed two protocols that consisted of two consecutive 6-min exercise bouts separated by a 6-min baseline at 0 W: 1) both bouts of heavy (work rate: 50% of lactate threshold to maximal VO(2)) leg cycling (L1-ex to L2-ex) and 2) heavy arm cranking followed by identical heavy leg cycling bout (A1-ex to A2-ex). Blood lactate concentrations before L1-ex, L2-ex, and A2-ex averaged 1.7 +/- 0.3, 5.6 +/- 0.9, and 6.7 +/- 1.4 meq/l, respectively. An "effective" time constant (tau) of VO(2) with the use of the monoexponential model in L2-ex (tau: 36.8 +/- 4.3 s) was significantly faster than that in L1-ex (tau: 52.3 +/- 8.2 s). Warm-up arm cranking did not facilitate the VO(2) kinetics for the following A2-ex [tau: 51.7 +/- 9.7 s]. The double-exponential model revealed no significant change of primary tau (phase II) VO(2) kinetics. Instead, the speeding seen in the effective tau during L2-ex was mainly due to a reduction of the VO(2) slow component. Near-infrared spectroscopy indicated that the degree of hyperemia in working leg muscles was significantly higher at the onset of L2-ex than A2-ex. In conclusion, facilitation of VO(2) kinetics during heavy exercise preceded by an intense warm-up exercise was caused principally by a reduction in the slow component, and it appears unlikely that this could be ascribed exclusively to systemic lactic acidosis.     

Comparison of oxygen uptake kinetics during knee extension and cycle exercise

The knee extension exercise (KE) model engenders different muscle and fiber recruitment patterns, blood flow, and energetic responses compared with conventional cycle ergometry (CE). This investigation had two aims: 1) to test the hypothesis that upright two-leg KE and CE in the same subjects would yield fundamentally different pulmonary O(2) uptake (pVo(2)) kinetics and 2) to characterize the muscle blood flow, muscle Vo(2) (mVo(2)), and pVo(2) kinetics during KE to investigate the rate-limiting factor(s) of pVo(2) on kinetics and muscle energetics and their mechanistic bases after the onset of heavy exercise. Six subjects performed KE and CE transitions from unloaded to moderate [< ventilatory threshold (VT)] and heavy (>VT) exercise. In addition to pVo(2) during CE and KE, simultaneous pulsed and echo Doppler methods, combined with blood sampling from the femoral vein, were used to quantify the precise temporal profiles of femoral artery blood flow (LBF) and mVo(2) at the onset of KE. First, the gain (amplitude/work rate) of the primary component of pVo(2) for both moderate and heavy exercise was higher during KE ( approximately 12 ml.W(-1).min(-1)) compared with CE ( approximately 10), but the time constants for the primary component did not differ. Furthermore, the mean response time (MRT) and the contribution of the slow component to the overall response for heavy KE were significantly greater than for CE. Second, the time constant for the primary component of mVo(2) during heavy KE [25.8 +/- 9.0 s (SD)] was not significantly different from that of the phase II pVo(2). Moreover, the slow component of pVo(2) evident for the heavy KE reflected the gradual increase in mVo(2). The initial LBF kinetics after onset of KE were significantly faster than the phase II pVo(2) kinetics (moderate: time constant LBF = 8.0 +/- 3.5 s, pVo(2) = 32.7 +/- 5.6 s, P < 0.05; heavy: LBF = 9.7 +/- 2.0 s, pVo(2) = 29.9 +/- 7.9 s, P < 0.05). The MRT of LBF was also significantly faster than that of pVo(2). These data demonstrate that the energetics (as gain) for KE are greater than for CE, but the kinetics of adjustment (as time constant for the primary component) are similar. Furthermore, the kinetics of muscle blood flow during KE are faster than those of pVo(2), consistent with an intramuscular limitation to Vo(2) kinetics, i.e., a microvascular O(2) delivery-to-O(2) requirement mismatch or oxidative enzyme inertia.     

Regulation of VO₂ kinetics by O₂ delivery: insights from acute hypoxia and heavy-intensity priming exercise in young men

This study examined the separate and combined effects of acute hypoxia (Hypo) and heavy-intensity "priming" exercise (Hvy) on pulmonary O(2) uptake (Vo(2p)) kinetics during moderate-intensity exercise (Mod). Breath-by-breath Vo(2p) and near-infrared spectroscopy-derived muscle deoxygenation {deoxyhemoglobin concentration [HHb]} were monitored continuously in 10 men (23 ± 4 yr) during repetitions of a Mod 1-Hvy-Mod 2 protocol, where each of the 6-min (Mod or Hvy) leg-cycling bouts was separated by 6 min at 20 W. Subjects were exposed to Hypo [fraction of inspired O(2) (Fi(O(2))) = 15%, Mod 2 + Hypo] or "sham" (Fi(O(2)) = 20.9%, Mod 2-N) 2 min following Hvy in half of these repetitions; Mod was also performed in Hypo without Hvy (Mod 1 + Hypo). On-transient Vo(2p) and [HHb] responses were modeled as a monoexponential. Data were scaled to a relative percentage of the response (0-100%), the signals were time-aligned, and the individual [HHb]-to-Vo(2) ratio was calculated. Compared with control (Mod 1), τVo(2p) and the O(2) deficit (26 ± 7 s and 638 ± 144 ml, respectively) were reduced (P < 0.05) in Mod 2-N (20 ± 5 s and 529 ± 196 ml) and increased (P < 0.05) in Mod 1 + Hypo (34 ± 14 s and 783 ± 184 ml); in Mod 2 + Hypo, τVo(2p) was increased (30 ± 8 s, P < 0.05), yet O(2) deficit was unaffected (643 ± 193 ml, P > 0.05). The modest "overshoot" in the [HHb]-to-Vo(2) ratio (reflecting an O(2) delivery-to-utilization mismatch) in Mod 1 (1.06 ± 0.04) was abolished in Mod 2-N (1.00 ± 0.05), persisted in Mod 2 + Hypo (1.09 ± 0.07), and tended to increase in Mod 1 + Hypo (1.10 ± 0.09, P = 0.13). The present data do not support an "O(2) delivery-independent" speeding of τVo(2p) following Hvy (or Hvy + Hypo); rather, this study suggests that local muscle O(2) delivery likely governs the rate of adjustment of Vo(2) at τVo(2p) greater than ～20 s.     

Influence of L-NAME on pulmonary O2 uptake kinetics during heavy-intensity cycle exercise.

We hypothesized that inhibition of nitric oxide synthase (NOS) by N(G)-nitro-L-arginine methyl ester (L-NAME) would alleviate the inhibition of mitochondrial oxygen uptake (Vo(2)) by nitric oxide and result in a speeding of phase II pulmonary Vo(2) kinetics at the onset of heavy-intensity exercise. Seven men performed square-wave transitions from unloaded cycling to a work rate requiring 40% of the difference between the gas exchange threshold and peak Vo(2) with and without prior intravenous infusion of L-NAME (4 mg/kg in 50 ml saline over 60 min). Pulmonary gas exchange was measured breath by breath, and Vo(2) kinetics were determined from the averaged response to two exercise bouts performed in each condition. There were no significant differences between the control (C) and L-NAME conditions (L) for baseline Vo(2), the duration of phase I, or the amplitude of the primary Vo(2) response. However, the time constant of the Vo(2) response in phase II was significantly smaller (mean +/- SE: C: 25.1 +/- 3.0 s; L: 21.8 +/- 3.3 s; P < 0.05), and the amplitude of the Vo(2) slow component was significantly greater (C: 240 +/- 47 ml/min; L: 363 +/- 24 ml/min; P < 0.05) after L-NAME infusion. These data indicate that inhibition of NOS by L-NAME results in a significant (13%) speeding of Vo(2) kinetics and a significant increase in the amplitude of the Vo(2) slow component in the transition to heavy-intensity cycle exercise in men. The speeding of the primary component Vo(2) kinetics after L-NAME infusion indicates that at least part of the intrinsic inertia to oxidative metabolism at the onset of heavy-intensity exercise may result from inhibition of mitochondrial Vo(2) by nitric oxide. The cause of the larger Vo(2) slow-component amplitude with L-NAME requires further investigation but may be related to differences in muscle blood flow early in the rest-to-exercise transition.     

Time-of-day effect on cardiac responses to progressive exercise

This study was designed to examine time-of-day effects on markers of cardiac functional capacity during a standard progressive cycle exercise test. Fourteen healthy, untrained young males (mean?±?SD: 17.9?±?0.7 yrs of age) performed identical maximal cycle tests in the morning (08:00-11:00?h) and late afternoon (16:00-19:00?h) in random order. Cardiac variables were measured at rest, submaximal exercise, and maximal exercise by standard echocardiographic techniques. No differences in morning and afternoon testing values at rest or during exercise were observed for oxygen uptake, heart rate, cardiac output, or markers of systolic and diastolic myocardial function. Values at peak exercise for Vo(2) at morning and afternoon testing were 3.20?±?0.49 and 3.24?±?0.55?L min(-1), respectively, for heart rate 190?±?11 and 188?±?15?bpm, and for cardiac output 19.5?±?2.8 and 19.8?±?3.5?L min(-1). Coefficients of variation for morning and afternoon values for these variables were similar to those previously published for test-retest reproducibility. This study failed to demonstrate evidence for significant time-of-day variation in Vo(2)max or cardiac function during standard progressive exercise testing in adolescent males.