Ventilation studied with circulatory occlusion during two intensities of exercise

Our purpose was to study the possible role of a pulmonary chemoreceptor in the control of ventilation during exercise. Respiratory gas exchange was measured breath-by-breath at two intensities of exercise with circulatory occlusion of the legs. Eight male subjects exercised on a cycle ergometer at 49 and 98 W for 12 min; circulation to the legs was occluded by thigh cuffs (26.7 kPa) for two min after six min of unoccluded exercise. PETCO2 and VO2 decreased and PETO2 increased significantly during occlusion at both workloads. Occlusion elicited marked hyperventilation, as evidenced by sharp increases in VE, VE/VCO2, and VE/VO2. A sudden sharp increase in PETCO2 was seen 12.3 +/- 0.5 and 6.5 +/- 1.2s after cuff release in all subjects during exercise at 49 and 98 W, respectively. At 49 W a post-occlusion inflection in VE was seen in 7 subjects 21.1 +/- 5.8s after the PETCO2 inflection. Three subjects showed an inflection in VE at 98 W 23.3 +/- 7.5 s after the PETCO2 inflection. There were significant increases in PETCO2, VO2, VCO2 and VE after cuff release. VE mirrored VCO2 better than VO2, post occlusion. On the basis of a significant lag time between inflections in PETCO2 and VE following cuff release, it is concluded that the influences of a pulmonary CO2 receptor were not seen.     

Determinants of poststimulus potentiation in humans during NREM sleep.

To test whether active hyperventilation activates the "afterdischarge" mechanism during non-rapid-eye-movement (NREM) sleep, we investigated the effect of abrupt termination of active hypoxia-induced hyperventilation in normal subjects during NREM sleep. Hypoxia was induced for 15 s, 30 s, 1 min, and 5 min. The last two durations were studied under both isocapnic and hypocapnic conditions. Hypoxia was abruptly terminated with 100% inspiratory O2 fraction. Several room air-to-hyperoxia transitions were performed to establish a control period for hyperoxia after hypoxia transitions. Transient hyperoxia alone was associated with decreased expired ventilation (VE) to 90 +/- 7% of room air. Hyperoxic termination of 1 min of isocapnic hypoxia [end-tidal PO2 (PETO2) 63 +/- 3 Torr] was associated with VE persistently above the hyperoxic control for four to six breaths. In contrast, termination of 30 s or 1 min of hypocapnic hypoxia [PETO2 49 +/- 3 and 48 +/- 2 Torr, respectively; end-tidal PCO2 (PETCO2) decreased by 2.5 or 3.8 Torr, respectively] resulted in hypoventilation for 45 s and prolongation of expiratory duration (TE) for 18 s. Termination of 5 min of isocapnic hypoxia (PETO2 63 +/- 3 Torr) was associated with central apnea (longest TE 200% of room air); VE remained below the hyperoxic control for 49 s. Termination of 5 min of hypocapnic hypoxia (PETO2 64 +/- 4 Torr, PETCO2 decreased by 2.6 Torr) was also associated with central apnea (longest TE 500% of room air). VE remained below the hyperoxic control for 88 s. We conclude that 1) poststimulus hyperpnea occurs in NREM sleep as long as hypoxia is brief and arterial PCO2 is maintained, suggesting the activation of the afterdischarge mechanism; 2) transient hypocapnia overrides the potentiating effects of afterdischarge, resulting in hypoventilation; and 3) sustained hypoxia abolishes the potentiating effects of after-discharge, resulting in central apnea. These data suggest that the inhibitory effects of sustained hypoxia and hypocapnia may interact to cause periodic breathing.     

Pulmonary clearance of 99mTc-DTPA: influence of background activity

To study the effects of circulatory occlusion on the time course and magnitude of postexercise O2 consumption (VO2) and blood lactate responses, nine male subjects were studied twice for 50 min on a cycle ergometer. On one occasion, leg blood flow was occluded with surgical thigh cuffs placed below the buttocks and inflated to 200 mmHg. The protocol consisted of a 10-min rest, 12 min of exercise at 40% peak O2 consumption (VO2 peak), and a 28-min resting recovery while respiratory gas exchange was determined breath by breath. Occlusion (OCC) spanned min 6-8 during the 12-min work bout and elicited mean blood lactate of 5.2 +/- 0.8 mM, which was 380% greater than control (CON). During 18 min of recovery, blood lactate after OCC remained significantly above CON values. VO2 was significantly lower during exercise with OCC compared with CON but was significantly higher during the 4 min of exercise after cuff release. VO2 was higher after OCC during the first 4 min of recovery but was not significantly different thereafter. Neither total recovery VO2 (gross recovery VO2 with no base-line subtraction) nor excess postexercise VO2 (net recovery VO2 above an asymptotic base line) was significantly different for OCC and CON conditions (13.71 +/- 0.45 vs. 13.44 +/- 0.61 liters and 4.93 +/- 0.26 vs. 4.17 +/- 0.35 liters, respectively). Manipulation of exercise blood lactate levels had no significant effect on the slow ("lactacid") component of the recovery VO2.     

Influence of body CO2 stores on ventilatory dynamics during exercise

Pulmonary CO2 flow (the product of cardiac output and mixed venous CO2 content) is purported to be an important determinant of ventilatory dynamics in moderate exercise. Depletion of body CO2 stores prior to exercise should thus slow these dynamics. We investigated, therefore, the effects of reducing the CO2 stores by controlled volitional hyperventilation on cardiorespiratory and gas exchange response dynamics to 100 W cycling in six healthy adults. The control responses of ventilation (VE), CO2 output (VCO2), O2 uptake (VO2), and heart rate were comprised of an abrupt increase at exercise onset, followed by a slower rise to the new steady state (t1/2 = 48, 43, 31, and 33 s, respectively). Following volitional hyperventilation (9 min, PETCO2 = 25 Torr), the steady-state exercise responses were unchanged. However, VE and VCO2 dynamics were slowed considerably (t1/2 = 76, 71 s) as PETCO2 rose to achieve the control exercise value. VO2 dynamics were slowed only slightly (t1/2 = 39 s), and heart rate dynamics were unaffected. We conclude that pulmonary CO2 flow provides a significant stimulus to the dynamics of the exercise hyperpnea in man.     

Ventilatory and gas exchange kinetics during exercise in chronic airways obstruction

The influence of chronic obstructive pulmonary disease (COPD) on exercise ventilatory and gas exchange kinetics was assessed in nine patients with stable airway obstruction (forced expired volume at 1 s = 1.1 +/- 0.33 liters) and compared with that in six normal men. Minute ventilation (VE), CO2 output (VCO2), and O2 uptake (VO2) were determined breath-by-breath at rest and after the onset of constant-load subanaerobic threshold exercise. The initial increase in VE, VCO2, and VO2 from rest (phase I), the subsequent slow exponential rise (phase II), and the steady-state (phase III) responses were analyzed. The COPD group had a significantly smaller phase I increase in VE (3.4 +/- 0.89 vs. 6.8 +/- 1.05 liters/min), VCO2 (0.10 +/- 0.03 vs. 0.22 +/- 0.03 liters/min), VO2 (0.10 +/- 0.03 vs. 0.24 +/- 0.04 liters/min), heart rate (HR) (6 +/- 0.9 vs. 16 +/- 1.4 beats/min), and O2 pulse (0.93 +/- 0.21 vs. 2.2 +/- 0.45 ml/beat) than the controls. Phase I increase in VE was significantly correlated with phase I increase in VO2 (r = 0.88) and HR (r = 0.78) in the COPD group. Most patients also had markedly slower phase II kinetics, i.e., longer time constants (tau) for VE (87 +/- 7 vs. 65 +/- 2 s), VCO2 (79 +/- 6 vs. 63 +/- 3 s), and VO2 (56 +/- 5 vs. 39 +/- 2 s) and longer half times for HR (68 +/- 9 vs. 32 +/- 2 s) and O2 pulse (42 +/- 3 vs. 31 +/- 2 s) compared with controls. However, tau VO2/tau VE and tau VCO2/tau VE were similar in both groups. The significant correlations of the phase I VE increase with HR and VO2 are consistent with the concept that the immediate exercise hyperpnea has a cardiodynamic basis. The slow ventilatory kinetics during phase II in the COPD group appeared to be more closely related to a slowed cardiovascular response rather than to any index of respiratory function. O2 breathing did not affect the phase I increase in VE but did slow phase II kinetics in most subjects. This confirms that the role attributed to the carotid bodies in ventilatory control during exercise in normal subjects also operates in patients with COPD.     

Relationship between hyperventilation and excessive CO2 output during recovery from repeated cycling sprints

The purpose of the present study was to examine whether excessive CO2 output (VCO2excess) is dominantly attributable to hyperventilation during the period of recovery from repeated cycling sprints. A series of four 10-sec cycling sprints with 30-sec passive recovery periods was performed two times. The first series and second series of cycle sprints (SCS) were followed by 360-sec passive recovery periods (first recovery and second recovery). Increases in blood lactate (DeltaLa) were 11.17+/-2.57 mM from rest to 5.5 min during first recovery and 2.07+/-1.23 mM from the start of the second SCS to 5.5 min during second recovery. CO2 output (VCO2) was significantly higher than O2 uptake (VO2) during both recovery periods. This difference was defined as VCO2excess. VCO2excess was significantly higher during first recovery than during second recovery. VCO2excess was added from rest to the end of first recovery and from the start of the second SCS to the end of second recovery (CO2excess). DeltaLa was significantly related to CO2excess (r=0.845). However, ventilation during first recovery was the same as that during second recovery. End-tidal CO2 pressure (PETCO2) significantly decreased from the resting level during the recovery periods, indicating hyperventilation. PETCO2 during first recovery was significantly higher than that during second recovery. It is concluded that VCO2excess is not simply determined by ventilation during recovery from repeated cycle sprints.     

Effect of inspiratory threshold loading on ventilatory kinetics during constant-load exercise

Humoral factors play an important role in the control of exercise hyperpnea. The role of neuromechanical ventilatory factors, however, is still being investigated. We tested the hypothesis that the afferents of the thoracopulmonary system, and consequently of the neuromechanical ventilatory loop, have an influence on the kinetics of oxygen consumption (VO2), carbon dioxide output (VCO2), and ventilation (VE) during moderate intensity exercise. We did this by comparing the ventilatory time constants (tau) of exercise with and without an inspiratory load. Fourteen healthy, trained men (age 22.6 +/- 3.2 yr) performed a continuous incremental cycle exercise test to determine maximal oxygen uptake (VO2max = 55.2 +/- 5.8 ml x min(-1) x kg(-1)). On another day, after unloaded warm-up they performed randomized constant-load tests at 40% of their VO2max for 8 min, one with and the other without an inspiratory threshold load of 15 cmH2O. Ventilatory variables were obtained breath by breath. Phase 2 ventilatory kinetics (VO2, VCO2, and VE) could be described in all cases by a monoexponential function. The bootstrap method revealed small coefficients of variation for the model parameters, indicating an accurate determination for all parameters. Paired Student's t-tests showed that the addition of the inspiratory resistance significantly increased the tau during phase 2 of VO2 (43.1 +/- 8.6 vs. 60.9 +/- 14.1 s; P < 0.001), VCO2 (60.3 +/- 17.6 vs. 84.5 +/- 18.1 s; P < 0.001) and VE (59.4 +/- 16.1 vs. 85.9 +/- 17.1 s; P < 0.001). The average rise in tau was 41.3% for VO2, 40.1% for VCO2, and 44.6% for VE. The tau changes indicated that neuromechanical ventilatory factors play a role in the ventilatory response to moderate exercise.     

Breath-by-breath gas exchange kinetics during constant-load work

In order to study respiratory transients during exercise, we examined breath-by-breath gas exchange kinetics during constant-load work. Five male subjects performed cycle ergometer tests which 6 min of constant-load work (150, 200, 250W) followed 50W base-line work. VCO2 and VO2 measured at the mouth ((VCO2)E, (VO2)E) and estimated at the alveolar level ((VCO2)A, (VO2)A) were computed breath-by-breath. The kinetic parameter (time constant) of first- and second-order exponential model was estimated using non-linear least-squares method. Our results demonstrated that a relative stability of PETO2, PETCO2, and R at their control values in the first phase. Independent of work intensities, breath-by-breath variation in gas exchange measured at the mouth was larger than those in gas exchange estimated at the alveolar level both at a non-steady state and a steady state. The time constants of (VO2)A and (VO2)E were varied with increase of work load intensity.     

Ventilatory and gas exchange responses under spontaneous and fixed breathing modes during arm exercise

To evaluate the difference of ventilatory and gas exchange response differences between arm and leg exercise, six healthy young men underwent ramp exercise testing at a rate of 15 W.min-1 on a cycle ergometer separately under either spontaneous (SPNT) or fixed (FIX) breathing modes, respectively. Controlled breathing was defined as a breathing frequency (fb; 30 breaths.min-1) which was neither equal to, nor a multiple of, cranking frequency (50 rev.min-1) to prevent coupling of locomotion and respiratory movement, i.e., so-called locomotor-respiratory coupling (LRC). Breath-by-breath oxygen uptake (VO2), ventilation (VE), CO2 output (VCO2), tidal volume (VT), fb and end-tidal PCO2 (PETCO2) were determined using a computerized metabolic cart. Arm exercise engendered a higher level of VO2 at each work rate than leg exercise under both FIX and SPNT conditions. However, FIX did not notably affect the VO2 response during either arm or leg exercise at each work rate compared to SPNT. During SPNT a significantly higher fb and lower PETCO2 during arm exercise was found compared with leg exercise up to a fb of 30 breaths.min-1 while VE and VT were nearly the same. During fixed breathing when fb was fixed at a higher rate than during SPNT, a significantly lower PETCO2 was observed during both exercise modes. These results suggest that: 1) FIX breathing does not affect the VO2 response during either arm or leg exercise even when non-synchronization between limb locomotion movement and breathing rate was adopted; 2) at a fb of 30 breaths.min-1 FIX breathing induced a hyperventilation resulting in a lower PETCO2 which was not associated with the metabolic rate during either arm or leg exercise, showing that VE during only leg exercise under the FIX condition was significantly higher than under the SPNT condition.     

Ventilatory response of spinal cord-lesioned subjects to electrically induced exercise

Seven human spinal cord-lesioned subjects (SPL) underwent electrically induced muscle contractions (EMC) of the quadriceps and hamstring muscles for 10 min: 5 min control, 2 min with venous return from the legs occluded, and 3 min postocclusion. Group mean changes in CO2 output compared with rest were +107 +/- 30.6, +21 +/- 25.7, and +192 +/- 37.0 (SE) ml/min during preocclusion, occlusion, and postocclusion EMC, respectively. Mean arterial CO2 partial pressure (PaCO2) obtained from catheterized radial arteries at 15- to 30-s intervals showed a significant (P less than 0.05) hypocapnia (36.2 Torr) during occlusion and a significant (P less than 0.05) hypercapnia (38.1 Torr) postocclusion relative to a group mean preocclusion EMC PaCO2 of 37.5 Torr. Relative to preocclusion EMC, expired ventilation (VE) decreased during occlusion and increased after release of occlusion. However, changes in VE always occurred after changes in end-tidal PCO2 (mean 41 s after occlusion and 10 s after release of occlusion). In the two subjects investigated during hyperoxia, the VE and PaCO2 responses to occlusion and release did not differ from normoxia. We conclude that the data do not support mediation of the EMC hyperpnea in SPL by humoral mechanisms that others have proposed for mediation of the exercise hyperpnea in spinal cord-intact humans.     

Influence of body size and gender on control of ventilation

Hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses are influenced by both metabolic activity and hormonal factors. By studying 67 subjects of both sexes, including those at the extremes of stature, we examined the influence of gender, CO2 production (VCO2), O2 consumption (VO2), body surface area (BSA), and vital capacity (VC) on resting ventilation (VE), HVR, and HCVR. We measured resting VE, VO2, and VCO2 and then performed isocapnic progressive hypoxic and hypercapnic ventilatory responses. The effect of stature was reflected in higher VE and metabolic rate (both P less than 0.001) in tall men compared with short men that was ablated by correction for BSA. Perhaps because their heights vary less than those of the men, tall women were not statistically distinguishable from short women in any of these measured parameters. Tall men tended to have greater hypoxic chemosensitivity than short men but this was not significantly different (P = 0.07). Gender affected the control of ventilation in a number of ways. Men had higher VE (P less than 0.05) and metabolic rate (P less than 0.001) than women. Even after correction for BSA men still had higher metabolic rates. Women had higher VE/VCO2 than men (P less than 0.05) and lower resting end-tidal Pco2 (PETCO2) values (P less than 0.05). Both A, the shape parameter of the hyperbolic HVR curve, and HVR determined from mouth occlusion pressure (AP) were greater in women than in men, although only AP reached statistical significance. However, corrections of A for BSA (P less than 0.05), VCO2 (P less than 0.01), and VC (P less than 0.001) amplified these differences.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of hyperoxia on substrate utilization during intense submaximal exercise

Six trained males [mean maximal O2 uptake (VO2max) = 66 ml X kg-1 X min-1] performed 30 min of cycling (mean = 76.8% VO2max) during normoxia (21.35 +/- 0.16% O2) and hyperoxia (61.34 +/- 1.0% O2). Values for VO2, CO2 output (VCO2), minute ventilation (VE), respiratory exchange ratio (RER), venous lactate, glycerol, free fatty acids, glucose, and alanine were obtained before, during, and after the exercise bout to investigate the possibility that a substrate shift is responsible for the previously observed enhanced performance and decreased RER during exercise with hyperoxia. VO2, free fatty acids, glucose, and alanine values were not significantly different in hyperoxia compared with normoxia. VCO2, RER, VE, and glycerol and lactate levels were all lower during hyperoxia. These results are interpreted to support the possibility of a substrate shift during hyperoxia.     

Effect of dopamine on transient ventilatory response to exercise

The effect of exogenous dopamine on the development of exercise hyperpnea was studied. Using a bicycle ergometer, five subjects performed repetitive square-wave work-load testing from unloaded pedaling to 80% of each subject's estimated anaerobic threshold. The breath-by-breath ventilation (VE), CO2 production (VCO2), and O2 consumption (VO2) responses were analyzed by curve fitting a first-order exponential model. Comparisons were made between control experiments and experiments with a 3-micrograms X kg-1 X min-1 intravenous infusion of dopamine. Steady-state VE, VCO2 and VO2 were unchanged by the dopamine infusion, both during unloaded pedaling and at the heavier work load. The time constants for the increase in VE (tau VE) and VCO2 (tau CO2) were significantly (P less than 0.05) slowed (tau VE = 56.5 +/- 16.4 s for control, and tau VE = 76.4 +/- 26.6 s for dopamine; tau CO2 = 51.5 +/- 10.6 s for control, and tau CO2 = 64.8 +/- 17.4 s for dopamine) (mean +/- SD), but the time constant for VO2 (tau O2) was not significantly affected (tau O2 = 27.5 +/- 11.7 s for control, and tau O2 = 31.0 +/- 10.1 s for dopamine). We conclude that ablation of carotid body chemosensitivity with dopamine slows the transient ventilatory response to exercise while leaving the steady-state response unaffected.     

Mechanistic basis for the gas exchange threshold in Thoroughbred horses.

The exercising Thoroughbred horse (TB) is capable of exceptional cardiopulmonary performance. However, because the ventilatory equivalent for O2 (VE/VO2) does not increase above the gas exchange threshold (Tge), hypercapnia and hypoxemia accompany intense exercise in the TB compared with humans, in whom VE/VO2 increases during supra-Tge work, which both removes the CO2 produced by the HCO buffering of lactic acid and prevents arterial partial pressure of CO2 (PaCO2) from rising. We used breath-by-breath techniques to analyze the relationship between CO2 output (VCO2) and VO2 [V-slope lactate threshold (LT) estimation] during an incremental test to fatigue (7 to approximately 15 m/s; 1 m x s(-1) x min(-1)) in six TB. Peak blood lactate increased to 29.2 +/- 1.9 mM/l. However, as neither VE/VO2 nor VE/VCO2 increased, PaCO2 increased to 56.6 +/- 2.3 Torr at peak VO2 (VO2 max). Despite the presence of a relative hypoventilation (i.e., no increase in VE/VO2 or VE/VCO2), a distinct Tge was evidenced at 62.6 +/- 2.7% VO2 max. Tge occurred at a significantly higher (P < 0.05) percentage of VO2 max than the lactate (45.1 +/- 5.0%) or pH (47.4 +/- 6.6%) but not the bicarbonate (65.3 +/- 6.6%) threshold. In addition, PaCO2 was elevated significantly only at a workload > Tge. Thus, in marked contrast to healthy humans, pronounced V-slope (increase VCO2/VO2) behavior occurs in TB concomitant with elevated PaCO2 and without evidence of a ventilatory threshold.     

Effects of inspiratory resistive load on respiratory control in hypercapnia and exercise

Eight healthy young men underwent two separate steady-state incremental exercise runs within the aerobic range on a treadmill with alternating periods of breathing with no load (NL) and with an inspiratory resistive load (IRL) of approximately 12 cmH2O.1-1.s. End-tidal PCO2 was maintained constant throughout each run at the eucapnic or a constant hypercapnic level by adding 0-5% CO2 to the inspired O2. Hypercapnia caused a steepening, as well as upward shift, relative to the corresponding eucapnic ventilation-CO2 output (VE - VCO2) relationship in NL and IRL. Compared with NL, the VE - VCO2 slope was depressed by IRL, more so in hypercapnic [-19.0 +/- 3.4 (SE) %] than in eucapnic exercise (-6.0 +/- 2.0%), despite a similar increase in the slope of the occlusion pressure at 100 ms - VCO2 (P100 - VCO2) relationship under both conditions. The steady-state hypercapnic ventilatory response at rest was markedly depressed by IRL (-22.6 +/- 7.5%), with little increase in P100 response. For a given inspiratory load, breathing pattern responses to separate or combined hypercapnia and exercise were similar. During IRL, VE was achieved by a greater tidal volume (VT) and inspiratory duty cycle (TI/TT) along with a lower mean inspiratory flow (VT/TI). The increase in TI/TT was solely because of a prolongation of inspiratory time (TI) with little change in expiratory duration for any given VT. The ventilatory and breathing pattern responses to IRL during CO2 inhalation and exercise are in favor of conservation of respiratory work.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined effects of female hormones and metabolic rate on ventilatory drives in women

Increased resting ventilation (VE) and hypoxic and hypercapnic ventilatory responses occur during pregnancy in association with elevations in female hormones and metabolic rate. To determine whether increases in progestin, estrogen, and metabolic rate produced a rise in VE and hypoxic ventilatory response (HVR) similar in magnitude to that observed at full-term pregnancy, we studied 12 postmenopausal women after 1 wk of treatment with placebo, progestin (20 mg tid medroxyprogesterone acetate), estrogen (1.25 mg bid conjugated equine estrogens), and combined progestin and estrogen. Progestin alone or with estrogen raised VE at rest and decreased end-tidal PCO2 (PETCO2) by 3.9 +/- 0.8 and 3.3 +/- 0.6 Torr, respectively (both P less than 0.05), accounting for approximately one-fourth of the rise in VE and three-fourths of the PETCO2 reduction seen at full-term pregnancy. The addition of mild exercise sufficient to raise metabolic rate by 33-36% produced the remaining three-fourths of the rise in VE but no further decline in PETCO2. Combined progestin and estrogen raised HVR and hypercapnic ventilatory response more consistently than progestin alone and could account for one-half of the increase in HVR seen at full-term pregnancy. Mild exercise alone did not raise HVR, but when exercise was combined with progestin and estrogen administration, HVR rose by amounts equal to that seen at full-term pregnancy. We concluded that female hormones together with mild elevation in metabolic rate were likely responsible for the pregnancy-associated increases in VE and HVR.     

Exertional dyspnea in mitochondrial myopathy: clinical features and physiological mechanisms

Exertional dyspnea limits exercise in some mitochondrial myopathy (MM) patients, but the clinical features of this syndrome are poorly defined, and its underlying mechanism is unknown. We evaluated ventilation and arterial blood gases during cycle exercise and recovery in five MM patients with exertional dyspnea and genetically defined mitochondrial defects, and in four control subjects (C). Patient ventilation was normal at rest. During exercise, MM patients had low Vo(2peak) (28 ± 9% of predicted) and exaggerated systemic O(2) delivery relative to O(2) utilization (i.e., a hyperkinetic circulation). High perceived breathing effort in patients was associated with exaggerated ventilation relative to metabolic rate with high VE/VO(2peak), (MM = 104 ± 18; C = 42 ± 8, P ≤ 0.001), and Ve/VCO(2peak)(,) (MM = 54 ± 9; C = 34 ± 7, P ≤ 0.01); a steeper slope of increase in ΔVE/ΔVCO(2) (MM = 50.0 ± 6.9; C = 32.2 ± 6.6, P ≤ 0.01); and elevated peak respiratory exchange ratio (RER), (MM = 1.95 ± 0.31, C = 1.25 ± 0.03, P ≤ 0.01). Arterial lactate was higher in MM patients, and evidence for ventilatory compensation to metabolic acidosis included lower Pa(CO(2)) and standard bicarbonate. However, during 5 min of recovery, despite a further fall in arterial pH and lactate elevation, ventilation in MM rapidly normalized. These data indicate that exertional dyspnea in MM is attributable to mitochondrial defects that severely impair muscle oxidative phosphorylation and result in a hyperkinetic circulation in exercise. Exaggerated exercise ventilation is indicated by markedly elevated VE/VO(2), VE/VCO(2), and RER. While lactic acidosis likely contributes to exercise hyperventilation, the fact that ventilation normalizes during recovery from exercise despite increasing metabolic acidosis strongly indicates that additional, exercise-specific mechanisms are responsible for this distinctive pattern of exercise ventilation.     

Relationship between arterial oxygen desaturation and ventilation during maximal exercise.

The purpose of the present study was to investigate the contribution of ventilation to arterial O2 desaturation during maximal exercise. Nine untrained subjects and 22 trained long-distance runners [age 18-36 yr, maximal O2 uptake (VO2max) 48-74 ml.min-1 x kg-1] volunteered to participate in the study. The subjects performed an incremental exhaustive cycle ergometry test at 70 rpm of pedaling frequency, during which arterial O2 saturation (SaO2) and ventilatory data were collected every minute. SaO2 was estimated with a pulse oximeter. A significant positive correlation was found between SaO2 and end-tidal PO2 (PETO2; r = 0.72, r2 = 0.52, P < 0.001) during maximal exercise. These statistical results suggest that approximately 50% of the variability of SaO2 can be accounted for by differences in PETO2, which reflects alveolar PO2. Furthermore, PETO2 was highly correlated with the ventilatory equivalent for O2 (VE/VO2; r = 0.91, P < 0.001), which indicates that PETO2 could be the result of ventilation stimulated by maximal exercise. Finally, SaO2 was positively related to VE/VO2 during maximal exercise (r = 0.74, r2 = 0.55, P < 0.001). Therefore, one-half of the arterial O2 desaturation occurring during maximal exercise may be explained by less hyperventilation, specifically for our subjects, who demonstrated a wide range of trained states. Furthermore, we found an indirect positive correlation between SaO2 and ventilatory response to CO2 at rest (r = 0.45, P < 0.05), which was mediated by ventilation during maximal exercise. These data also suggest that ventilation is an important factor for arterial O2 desaturation during maximal exercise.     

Effects of sodium bicarbonate ingestion on hyperventilation and recovery of blood pH after a short-term intense exercise

To determine the relationship between hyperventilation and recovery of blood pH during recovery from a heavy exercise, short-term intense exercise (STIE) tests were performed after human subjects ingested 0.3 g.kg(-1) body mass of either NaHCO3 (Alk) or CaCO3 (Pla). Ventilation (VE)-CO2 output (VCO2) slopes during recovery following STIE were significantly lower in Alk than in Pla, indicating that hyperventilation is attenuated under the alkalotic condition. However, this reduction of the slope was the result of unchanged VE and a small increase in VCO2. A significant correlation between VE and blood pH was found during recovery in both conditions. While there was no difference between the VE-pH slopes in the two conditions, VE at the same pH was higher in Alk than in Pla. Furthermore, the values of pH during recovery in both conditions increased toward the preexercise levels of each condition. Thus, although VE-VCO2 slope was decreased under the alkalotic condition, this could not be explained by the ventilatory depression attributed to increase in blood pH. We speculate that hyperventilation after the end of STIE is determined by the VE-pH relationship that was set before STIE or the intensity of the exercise performed.     

Effect of pH on metabolic and cardiorespiratory responses during progressive exercise

Six healthy male subjects performed three exercise tests in which the power output was increased by 100 kpm/min each minute until exhaustion. The studies were carried out after oral administration of CaCO3 (control), NH4Cl (metabolic acidosis), and NaHCO3 (metabolic alkalosis). Ventilation (VE), O2 intake (VO2), and CO2 output (VCO2) were monitored continuously. Arterialized-venous blood samples were drawn at specific times and analyzed for pH, PCO2, and lactate concentration. Resting pH (mean +/- SE) was lowest in acidosis (7.29 +/- 0.01) and highest in alkalosis (7.46 +/- 0.02). A lower peak power output (kpm/min) was achieved in acidosis (1,717 +/- 95) compared with control (1,867 +/- 120) alkalosis (1,867 +/- 125). Submaximal VO2 and VCO2 were similar, but peak VO2 and VCO2 were lower in acidosis. Plasma lactate concentration was lower at rest and during exercise in acidosis. Although lactate accumulation was reduced in acidosis, increases in hydrogen ion concentration were similar in the three conditions. We conclude that acid-base changes influence the maximum power output that may be sustained in incremental dynamic exercise and modify plasma lactate appearance, but have little effect on hydrogen ion appearance in plasma.