Computer simulation of O2 transport and utilization mechanisms at the onset of exercise.

During transitions in work rate, O2 uptake (VO2) kinetics at the working tissue level might be rate limited by O2 transport and/or by O2 utilization. A computer model with parallel working and non-working tissue compartments, connected to an ideal lung by a variable-sized venous blood volume, was developed to study this. The time constant for working tissue O2 demand (tau T) was set by a first-order linear metabolic response. The model attempted to replicate the VO2 response at the alveolar level of a single subject performing step transitions on a cycle ergometer from 25 to 105 W [total lag time (equivalent to 63% increase above baseline) = 40.2 s]. Measured cardiac output kinetics (total lag time = 44.1 s) were used as a model parameter. Blood flow to the nonworking tissue (QNW) was kept constant at 4.5 or 5.0 l/min. A critical PO2 of 20 Torr was set, and the Bohr effect on the O2-hemoglobin dissociation curve was included. The "best" simulation had tau T = 36 s, QNW = 4.5 l/min, and venous blood volume = 2 liters and was not O2 transport limited. The approximation to the real data was good in all but the phase 1 response, where the model underpredicted the measured response. However, when QNW was increased to 5.0 l/min, the model was O2 transport limited; yet the predicted VO2 response at the alveolar level was not notably different from the subject's data.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peripheral circulatory factors limit rate of increase in muscle O2 uptake at onset of heavy exercise

We used anexercise paradigm with repeated bouts of heavy forearm exercise to testthe hypothesis that alterations in local acid-base environment thatremain after the first exercise result in greater blood flow andO₂ delivery at the onset of the second bout of exercise.Two bouts of handgrip exercise at 75% peak workload were performed for5 min, separated by 5 min of recovery. We continuously measured bloodflow using Doppler ultrasound and sampled venous blood forO₂ content, PCO₂, pH, and lactateand potassium concentrations, and we calculated muscle O₂uptake (O₂). Forearm blood flow waselevated before the second exercise compared with the first andremained higher during the first 30 s of exercise (234 ± 18 vs. 187 ± 4 ml/min, P < 0.05). Flow was notdifferent at 5 min. Arteriovenous O₂ content difference waslower before the second bout (4.6 ± 0.9 vs. 7.2 ± 0.7 mlO₂/dl) and higher by 30 s of exercise(11.2 ± 0.7 vs. 10.8 ± 0.7 ml O₂/dl,P < 0.05). Muscle O₂was unchanged before the start of exercise but was elevated during thefirst 30 s of the transition to the second exercise bout(26.0 ± 2.1 vs. 20.0 ± 0.9 ml/min, P < 0.05). Changes in venous blood PCO₂, pH, andlactate concentration were consistent with reduced reliance onanaerobic glycolysis at the onset of the second exercise bout. Thesedata show that limitations of muscle blood flow can restrict theadaptation of oxidative metabolism at the onset of heavy muscular exertion.

     

Effects of compression on muscle tissue oxygenation at the onset of exercise

The effects of compression on gastrocnemius medialis muscle oxygenation and hemodynamics during a short-term dynamic exercise was investigated in a sample of 15 male subjects (mean ± SD; age 25.8 ± 4.9 years; mass 70.6 ± 4.3 kg). Elastic compression sleeves were used to apply multiple levels of compression to the calf muscles during exercise, and noncompressive garments were used for the control condition. Tissue hemoglobin oxygen saturation was measured as the relative "tissue oxygen index" (TOI) with a near-infrared spectrometer. The recovery of TOI during exercise was determined from the slope of oxygenation recovery in a nonoccluded situation. The TOI recovery rate during the first 2 minutes of the exercise was 24% higher (p = 0.042) for the compression condition than for the control condition. A significant correlation (r = 0.61, p = 0.012) between the level of compression and the tissue oxygenation recovery during exercise was observed. Muscle energy use was determined from the rate of decline of TOI immediately upon arterial occlusion during early exercise. Muscle energy use measured during the occluded situation was not significantly influenced by compression. Based on these results, it was concluded that compression induced changes in tissue blood flow and perfusion appear to result in improved oxygenation during short-term exercise. Assuming that increased muscle oxygen availability positively influences performance, compression of muscles may enhance performance especially in sports that require repeated short bouts of exercise.     

O2 uptake and blood pressure regulation at the onset of exercise: interaction of circadian rhythm and priming exercise

Circadian rhythm has an influence on several physiological functions that contribute to athletic performance. We tested the hypothesis that circadian rhythm would affect blood pressure (BP) responses but not O(2) uptake (Vo(2)) kinetics during the transitions to moderate and heavy cycling exercises. Nine male athletes (peak Vo(2): 60.5 ± 3.2 ml·kg(-1)·min(-1)) performed multiple rides of two different cycling protocols involving sequences of 6-min bouts at moderate or heavy intensities interspersed by a 20-W baseline in the morning (7 AM) and evening (5 PM). Breath-by-breath Vo(2) and beat-by-beat BP estimated by finger cuff plethysmography were measured simultaneously throughout the protocols. Circadian rhythm did not affect Vo(2) onset kinetics determined from the phase II time constant (τ(2)) during either moderate or heavy exercise bouts with no prior priming exercise (τ(2) moderate exercise: morning 22.5 ± 4.6 s vs. evening 22.2 ± 4.6 s and τ(2) heavy exercise: morning 26.0 ± 2.7 s vs. evening 26.2 ± 2.6 s, P > 0.05). Priming exercise induced the same robust acceleration in Vo(2) kinetics during subsequent moderate and heavy exercise in the morning and evening. A novel finding was an overshoot in BP (estimated from finger cuff plethysmography) in the first minutes of each moderate and heavy exercise bout. After the initial overshoot, BP declined in association with increased skin blood flow between the third and sixth minute of the exercise bout. Priming exercise showed a greater effect in modulating the BP responses in the evening. These findings suggest that circadian rhythm interacts with priming exercise to lower BP during exercise after an initial overshoot with a greater influence in the evening associated with increased skin blood flow.     

Effect of duration of exercise on excess postexercise O2 consumption

This study was undertaken to determine the effect of exercise duration on the time course and magnitude of excess postexercise O2 consumption (EPOC). Six healthy male subjects exercised on separate days for 80, 40, and 20 min at 70% of maximal O2 consumption on a cycle ergometer. A control experiment without exercise was performed. O2 uptake, respiratory exchange ratio (R), and rectal temperature were monitored while the subjects rested in bed 24 h postexercise. An increase in O2 uptake lasting 12 h was observed for all exercise durations, but no increase was seen after 24 h. The magnitude of 12-h EPOC was proportional to exercise duration and equaled 14.4 +/- 1.2, 6.8 +/- 1.7, and 5.1 +/- 1.2% after 80, 40, and 20 min of exercise, respectively. On the average, 12-h EPOC equaled 15.2 +/- 2.0% of total exercise O2 consumption (EOC). There was no difference in EPOC:EOC for different exercise durations. A linear decrease with exercise duration was observed in R between 2 and 24 h postexercise. No change was observed in recovery rectal temperature. It is concluded that EPOC increases linearly with exercise duration at a work intensity of 70% of maximal O2 consumption.     

Effects of priming exercise on VO2 kinetics and O2 deficit at the onset of stepping and cycling

Breath-by-breath O2 uptake (VO2) kinetics and increase of blood lactate concentration (delta Lab) were determined at the onset of square-wave stepping (S) or cycling (C) exercise on six male subjects during 1) transition from rest (R) to constant work load, 2) transition from lower to heavier work loads, wherein the baseline VO2 (VO2 s) was randomly chosen between 20 and 65% of the subjects' maximal O2 uptake (VO2 max), and 3) inverse transition from higher to lower work loads and/or to rest. VO2 differences between starting and arriving levels were 20-60% VO2 max. In C, the VO2 on-response became monotonically slower with increasing VO2 s, the half time (t1/2) increasing from approximately 22 s for VO2 s = R to approximately 63 s when VO2 s approximately equal to 50% VO2 max. In S, the fastest VO2 kinetics (t1/2 = 16 s) was attained from VO2 s = 15-30% VO2 max, the t1/2 being approximately 25 s when starting from R or from 50% VO2 max. The slower VO2 kinetics in C were associated with a much larger delta Lab. The VO2 kinetics in recovery were essentially the same in all cases and could be approximated by a double exponential with t1/2 of 21.3 +/- 6 and 93 +/- 45 s for the fast and slow components, respectively. It is concluded that the O2 deficit incurred is the sum of three terms: 1) O2 stores depletion, 2) O2 equivalent of early lactate production, and 3) O2 equivalent of phosphocreatine breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle chemoreflex elevates muscle blood flow and O2 uptake at exercise onset in nonischemic human forearm.

We tested the hypothesis that increases in forearm blood flow (FBF) during the adaptive phase at the onset of moderate exercise would allow a more rapid increase in muscle O2 uptake (VO2 mus). Fifteen subjects completed forearm exercise in control (Con) and leg occlusion (Occ) conditions. In Occ, exercise of ischemic calf muscles was performed before the onset of forearm exercise to activate the muscle chemoreflex evoking a 25-mmHg increase in mean arterial pressure that was sustained during forearm exercise. Eight subjects who increased FBF during Occ compared with Con in the adaptation phase by >30 ml/min were considered "responders." For the responders, a higher VO2 mus accompanied the higher FBF only during the adaptive phase of the Occ tests, whereas there was no difference in the baseline or steady-state FBF or VO2 mus between Occ and Con. Supplying more blood flow at the onset of exercise allowed a more rapid increase in VO2 mus supporting our hypothesis that, at least for this type of exercise, O2 supply might be limiting.     

Effect of beta-blockade on the drift in O2 consumption during prolonged exercise

The effect of beta-adrenergic blockade on the drift in O2 consumption (VO2 drift) typically observed during prolonged constant-rate exercise was studied in 14 healthy males in moderate heat at 40% of maximal O2 consumption (VO2max). After an initial maximum cycle ergometer test to determine the subjects' control VO2max, subjects were administered each of three medications: placebo, atenolol (100 mg once daily), and propranolol (80 mg twice daily), in a randomized double-blind fashion. Each medication period was 5 days in length and was followed by a 4-day washout period. On the 3rd day of each medication period, subjects performed a maximal cycle ergometer test. On the final day of each medication period, subjects exercised at 40% of their control VO2max for 90 min on a cycle ergometer in a warm (31.7 +/- 0.3 degrees C) moderately humid (44.7 +/- 4.7%) environment. beta-Blockade caused significant (P less than 0.05) reductions in VO2max, maximal minute ventilation (VEmax), maximal heart rate (HRmax), and maximal exercise time. Significantly greater decreases in VO2max, VEmax, and HRmax were associated with the propranolol compared with the atenolol treatment. During the 90-min submaximal rides, beta-blockade significantly reduced heart rate. Substantially lower values for O2 consumption (VO2) and minute ventilation (VE) were observed with propranolol compared with atenolol or placebo. Furthermore, VO2 drift and HR drift were observed under atenolol and placebo conditions but not with propranolol. Respiratory exchange ratio decreased significantly over time during the placebo and atenolol trials but did not change during the propranolol trial.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phase I dynamics of cardiac output, systemic O2 delivery, and lung O2 uptake at exercise onset in men in acute normobaric hypoxia

We tested the hypothesis that vagal withdrawal plays a role in the rapid (phase I) cardiopulmonary response to exercise. To this aim, in five men (24.6+/-3.4 yr, 82.1+/-13.7 kg, maximal aerobic power 330+/-67 W), we determined beat-by-beat cardiac output (Q), oxygen delivery (QaO2), and breath-by-breath lung oxygen uptake (VO2) at light exercise (50 and 100 W) in normoxia and acute hypoxia (fraction of inspired O2=0.11), because the latter reduces resting vagal activity. We computed Q from stroke volume (Qst, by model flow) and heart rate (fH, electrocardiography), and QaO2 from Q and arterial O2 concentration. Double exponentials were fitted to the data. In hypoxia compared with normoxia, steady-state fH and Q were higher, and Qst and VO2 were unchanged. QaO2 was unchanged at rest and lower at exercise. During transients, amplitude of phase I (A1) for VO2 was unchanged. For fH, Q and QaO2, A1 was lower. Phase I time constant (tau1) for QaO2 and VO2 was unchanged. The same was the case for Q at 100 W and for fH at 50 W. Qst kinetics were unaffected. In conclusion, the results do not fully support the hypothesis that vagal withdrawal determines phase I, because it was not completely suppressed. Although we can attribute the decrease in A1 of fH to a diminished degree of vagal withdrawal in hypoxia, this is not so for Qst. Thus the dual origin of the phase I of Q and QaO2, neural (vagal) and mechanical (venous return increase by muscle pump action), would rather be confirmed.     

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.     

Effect of prior multiple-sprint exercise on pulmonary O2 uptake kinetics following the onset of perimaximal exercise.

We hypothesized that the metabolic acidosis resulting from the performance of multiple-sprint exercise would enhance muscle perfusion and result in a speeding of pulmonary oxygen uptake (VO2)kinetics during subsequent perimaximal-intensity constant work rate exercise, if O2 availability represented a limitation to VO2 kinetics in the control (i.e., no prior exercise) condition. On two occasions, seven healthy subjects completed two bouts of exhaustive cycle exercise at a work rate corresponding to approximately 105% of the predetermined Vo2 peak, separated by 3 x 30-s maximal sprint cycling and 15-min recovery (MAX1 and MAX2). Blood lactate concentration (means +/- SD: MAX1: 1.3 +/- 0.4 mM vs. MAX2: 7.7 +/- 0.9 mM; P < 0.01) was significantly greater immediately before, and heart rate was significantly greater both before and during, perimaximal exercise when it was preceded by multiple-sprint exercise. Near-infrared spectroscopy also indicated that muscle blood volume and oxygenation were enhanced when perimaximal exercise was preceded by multiple-sprint exercise. However, the time constant describing the primary component (i.e., phase II) increase in VO2 was not significantly different between the two conditions (MAX1: 33.8 +/- 5.5 s vs. MAX2: 33.2 +/- 7.7 s). Rather, the asymptotic "gain" of the primary Vo2 response was significantly increased by the performance of prior sprint exercise (MAX1: 8.1 +/- 0.9 ml.min(-1).W(-1) vs. MAX2: 9.0 +/- 0.7 ml.min(-1).W(-1); P < 0.05), such that VO2 was projecting to a higher "steady-state" amplitude with the same time constant. These data suggest that priming exercise, which apparently increases muscle O2 availability, does not influence the time constant of the primary-component VO2 response but does increase the amplitude to which VO2 may rise following the onset of perimaximal-intensity cycle exercise.     

Simultaneous determination of the kinetics of cardiac output, systemic O(2) delivery, and lung O(2) uptake at exercise onset in men

We tested whether the kinetics of systemic O(2) delivery (QaO(2)) at exercise start was faster than that of lung O(2) uptake (Vo(2)), being dictated by that of cardiac output (Q), and whether changes in Q would explain the postulated rapid phase of the Vo(2) increase. Simultaneous determinations of beat-by-beat (BBB) Q and QaO(2), and breath-by-breath Vo(2) at the onset of constant load exercises at 50 and 100 W were obtained on six men (age 24.2 +/- 3.2 years, maximal aerobic power 333 +/- 61 W). Vo(2) was determined using Gr?nlund's algorithm. Q was computed from BBB stroke volume (Q(st), from arterial pulse pressure profiles) and heart rate (f(h), electrocardiograpy) and calibrated against a steady-state method. This, along with the time course of hemoglobin concentration and arterial O(2) saturation (infrared oximetry) allowed computation of BBB QaO(2). The Q, QaO(2) and Vo(2) kinetics were analyzed with single and double exponential models. f(h), Q(st), Q, and Vo(2) increased upon exercise onset to reach a new steady state. The kinetics of QaO(2) had the same time constants as that of Q. The latter was twofold faster than that of Vo(2). The Vo(2) kinetics were faster than previously reported for muscle phosphocreatine decrease. Within a two-phase model, because of the Fick equation, the amplitude of phase I Q changes fully explained the phase I of Vo(2) increase. We suggest that in unsteady states, lung Vo(2) is dissociated from muscle O(2) consumption. The two components of Q and QaO(2) kinetics may reflect vagal withdrawal and sympathetic activation.     

Adaptation of pulmonary O2 uptake kinetics and muscle deoxygenation at the onset of heavy-intensity exercise in young and older adults.

The purpose was to examine the adaptation of pulmonary O(2) uptake (Vo(2p)) and deoxygenation of the vastus lateralis muscle at the onset of heavy-intensity, constant-load cycling exercise in young (Y; 24 +/- 4 yr; mean +/- SD; n = 5) and older (O; 68 +/- 3 yr; n = 6) adults. Subjects performed repeated transitions on 4 separate days from 20 W to a work rate corresponding to heavy-intensity exercise. Vo(2p) was measured breath by breath. The concentration changes in oxyhemoglobin, deoxyhemoglobin (HHb), and total hemoglobin/myoglobin were determined by near-infrared spectroscopy (Hamamatsu NIRO-300). Vo(2p) data were filtered, interpolated to 1 s, and averaged to 5-s bins. HHb-near-infrared spectroscopy data were filtered and averaged to 5-s bins. A monoexponential model was used to fit Vo(2p) [phase 2, time constant (tau) of Vo(2p)] and HHb [following the time delay (TD) from exercise onset to the start of an increase in HHb] data. The tauVo(2p) was slower (P < 0.001) in O (49 +/- 8 s) than Y (29 +/- 4 s). The HHb TD was similar in O (8 +/- 3 s) and Y (7 +/- 1 s); however, the tau HHb following TD was faster (P < 0.05) in O (8 +/- 2 s) than Y (14 +/- 2 s). The slower Vo(2p) kinetics and faster muscle deoxygenation in O compared with Y during heavy-intensity exercise imply that the kinetics of muscle perfusion are slowed relatively more than those of Vo(2p) in O. This suggests that the slowed Vo(2p) kinetics in O may be a consequence of a slower adaptation of local muscle blood flow relative to that in Y.     

Skeletal muscle vasodilation at the onset of exercise

The purpose of this study was to determinewhether -adrenergic or muscarinic receptors are involved in skeletalmuscle vasodilation at the onset of exercise. Mongrel dogs(n = 7) were instrumented with flow probes on both externaliliac arteries and a catheter in one femoral artery. Propranolol (1 mg), atropine (500 µg), both drugs, or saline was infusedintra-arterially immediately before treadmill exercise at 3 miles/h,0% grade. Immediate and rapid increases in iliac blood flow occurredwith initiation of exercise under all conditions. Peak blood flows werenot significantly different among conditions (682 ± 35, 646 ± 49, 637 ± 68, and 705 ± 50 ml/min, respectively). Although thedoses of antagonists employed had no effect on heart rate or systemicblood pressure, they were adequate to abolish agonist-induced increasesin iliac blood flow. Because neither propranolol nor atropine affected iliac blood flow, we conclude that activation of -adrenergic andmuscarinic receptors is not essential for the rapid vasodilation inactive skeletal muscle at the onset of exercise in dogs.

     

Effects of malaria on O2 consumption and brown adipose tissue activity in mice

Increased energy expenditure often occurs during illness or after injection of endotoxin and can contribute to the generation of fever. In laboratory rats and mice the thermogenic response has been attributed to the sympathetic activation of brown adipose tissue (BAT), although mice often fail to show pyrexia. In this study the effects of malaria on O2 consumption and BAT were studied in mice inoculated with Plasmodium berghei. Parasitemia was maximal (greater than 50% of erythrocytes showing positive Leishman staining) 72 h after inoculation. Up to this time body weight and food intake were similar to values for control mice, although colonic temperatures were slightly depressed in infected mice. Thereafter, infected mice showed marked hypophagia, loss of body weight, and severe hypothermia; colonic temperature was less than 31 degrees C at 96 h when the experiment was terminated. Resting O2 consumption (VO2) measured at 24 degrees C was slightly elevated in infected mice 12 h after inoculation and reached a peak value (31% above controls) at 48 h. VO2 returned to the same value as controls at 96 h. In vitro thermogenic activity of BAT (assessed from binding of guanosine diphosphate to isolated mitochondria) was not significantly altered in infected mice. These data demonstrate a marked thermogenic response to malarial infection, but this is not accompanied by fever in mice and is dissociated from stimulation of BAT activity.