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

Five 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 a discontinuous inspiratory elastic load (IEL) of approximately 10 cmH2O/l. 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 IEL. Compared with NL, the VE-VCO2 slope was depressed by IEL, more so in hypercapnic [-28.7 +/- 7.2 (SE) %] than in eucapnic exercise (-16.0 +/- 2.8%). The steady-state hypercapnic ventilatory response at rest was also markedly depressed (-32.1 +/- 11.2%). Occlusion pressure response was augmented in response to IEL during eucapnic exercise (88.7 +/- 13.3%) but not during CO2 inhalation at rest or during exercise. Breathing pattern characteristics were similar regardless of the type of stimulus input and the level of inspiratory load. Results are consistent with the notion that the control of VE and breathing pattern may both be influenced by a balance between the prevailing chemical drive and a propensity of the controller to reduce respiratory effort.     

Breathing pattern during exercise in young black and Caucasian subjects

Lung volumes in sex-, age-, height-, and weight-matched Black subjects are 10-15% lower than those in Caucasians. To determine whether this decreased lung volume affected the ventilatory adaptation to exercise, minute ventilation (VE), its components, frequency (f) and tidal volume (VT), and breathing pattern were observed during incremental cycle-ergometer exercise. Eighteen Caucasian (age 8-30 yr) and 14 Black (age 8-25 yr) subjects were studied. Vital capacity (VC) was lower (P less than 0.001) in the Black subjects [90.6 +/- 8.6 (SD) vs. 112.9 +/- 9.9% predicted], whereas functional residual capacity/total lung capacity was higher (P less than 0.05). VE, mixed expired O2 and CO2, VT, f, and inspiratory (TI), expiratory (TE), and total respiratory cycle (TT) duration were measured during the last 30 s of each 2-min load. Statistical comparisons with increasing power output were made at rest and from 0.6 to 2.4 W/kg in 0.3-W/kg increments. VE was higher in Blacks at all work loads and reached significance (P less than 0.05) at 0.6 and 1.5 W/kg. VE/VO2 was also higher throughout exercise, reaching significance (P less than 0.01) at 1.2, 1.5, and 1.8 W/kg. The Black subjects attained any given level of VE with a higher f (P less than 0.001) and lower VT. TI and TE were shortened proportionately so that TI/TT was not different. Differences in lung volume and the ventilatory response to exercise in these Black and Caucasian subjects suggest differences in the respiratory pressure-volume relationships or that the Black subjects may breathe higher on their pressure-volume curve.     

Hyperpnoea and CO2 sensitivity of the respiratory centres during exercise

The aim of this study was to specify whether exercise hyperpnoea was related to the CO2 sensitivity of the respiratory centres measured during steady-state exercise of mild intensity. Thus, ventilation (VE), breathing pattern [tidal volume (VT), respiratory frequency (f), inspiratory time (TI), total time of the respiratory cycle (TTOT), VT/TI, TI/TTOT] and CO2 sensitivity of the respiratory centres determined by the rebreathing method were measured at rest (SCO2re) and during steady-state exercise (SCO2ex) of mild intensity [CO2 output (VCO2) = 20 ml.kg-1.min-1] in 11 sedentary male subjects (aged 20-34 years). The results showed that SCO2re and SCO2ex were not significantly different. During exercise, there was no correlation between VE and SCO2ex and, for the same VCO2, all subjects had very close VE values normalized for body mass (bm), regardless of their SCO2ex (VEbm0.75 = 1.44 l.min-1.kg-1 SD 0.10). A highly significant positive correlation between SCO2ex and VT (normalised for bm) (r = 0.80, P less than 0.01), TI (r = 0.77, P less than 0.01) and TTOT (r = 0.77, P less than 0.01) existed, as well as a highly significant negative correlation between SCO2ex and (normalised for bm-0.25) (r = -0.73, P less than 0.01). We conclude that the hyperpnoea during steady-state exercise of mild intensity is not related to the SCO2ex. The relationship between breathing pattern and SCO2ex suggests that the breathing pattern could influence the determination of the SCO2ex. This finding needs further investigation.     

Effect of inspiratory resistive loading on control of ventilation during progressive exercise

Eight healthy volunteers performed gradational tests to exhaustion on a mechanically braked cycle ergometer, with and without the addition of an inspiratory resistive load. Mean slopes for linear ventilatory responses during loaded and unloaded exercise [change in minute ventilation per change in CO2 output (delta VE/delta VCO2)] measured below the anaerobic threshold were 24.1 +/- 1.3 (SE) = l/l of CO2 and 26.2 +/- 1.0 l/l of CO2, respectively (P greater than 0.10). During loaded exercise, decrements in VE, tidal volume, respiratory frequency, arterial O2 saturation, and increases in end-tidal CO2 tension were observed only when work loads exceeded 65% of the unloaded maximum. There was a significant correlation between the resting ventilatory response to hypercapnia delta VE/delta PCO2 and the ventilatory response to VCO2 during exercise (delta VE/delta VCO2; r = 0.88; P less than 0.05). The maximal inspiratory pressure generated during loading correlated with CO2 sensitivity at rest (r = 0.91; P less than 0.05) and with exercise ventilation (delta VE/delta VCO2; r = 0.83; P less than 0.05). Although resistive loading did not alter O2 uptake (VO2) or heart rate (HR) as a function of work load, maximal VO2, HR, and exercise tolerance were decreased to 90% of control values. We conclude that a modest inspiratory resistive load reduces maximum exercise capacity and that CO2 responsiveness may play a role in the control of breathing during exercise when airway resistance is artificially increased.     

Effect of mechanical loading on expiratory and inspiratory muscle activity during NREM sleep

We investigated the effect of acute and sustained inspiratory resistive loading (IRL) on the activity of expiratory abdominal muscles (EMGab) and the diaphragm (EMGdi) and on ventilation during wakefulness and non-rapid-eye-movement (NREM) sleep in healthy subjects. EMGdi and EMGab were measured with esophageal and transcutaneous electrodes, respectively. During wakefulness, EMGdi increased in response to acute loading (18 cmH2O.l-1.s) (+23%); this was accompanied by preservation of tidal volume (VT) and minute ventilation (VE). During NREM sleep, no augmentation was noted in EMGdi or EMGab. Inspiratory time (TI) was prolonged (+5%), but this was not sufficient to prevent a decrease in both VT and VE (-21 and -20%, respectively). During sustained loading (12 cmH2O.l-1 s) in NREM sleep, control breaths (C) were compared with the steady-state loaded breaths (SS) defined by breaths 41-50. Steady-state IRL was associated with augmentation of EMGdi (12%) and EMGab (50%). VT returned to control levels, expiratory time shortened, and breathing frequency increased. The net result was the increase in VE above control levels (+5%, P less than 0.01). No change was noted in end-tidal CO2 or O2. We concluded that 1) wakefulness is a prerequisite for immediate load compensation (in its absence, TI prolongation is the only compensatory response) and 2) during sustained IRL, the augmentation of EMGdi and EMGab can lead to complete ventilatory recovery without measurable changes in chemical stimuli.     

Postnatal maturation of ventilation and breathing pattern in kittens: influence of sleep

Ventilation and breathing pattern were studied in kittens at 1, 2, 3, 4, and 8 wk of life during quiet wakefulness (W), quiet sleep (QS), and active sleep (AS) with the barometric method. Tidal volume (VT), respiratory frequency (f), ventilation (VE), inspiratory time (TI), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory "duty cycle" (TI/TT) were measured. VT, VE, TI, TE, and VT/TI increased; f decreased and TI/TT remained constant during postnatal development in wakefulness and in both sleep states. No significant difference was observed between AS and QS for all the ventilatory parameters except TI/TT, which was greater in QS than in AS at 2 wk. VE was larger in W than in both AS and QS at all ages. This was mainly due to a greater f, TI/TT remaining constant. VT/TI, which represents an index of the central inspiratory activity, was larger in W than in sleep, VT not being significantly different whatever the stage of consciousness. The results of this study show that in the kitten 1) unlike in the adult cat, ventilation and breathing pattern are similar in QS and in AS; 2) in sleep, the central inspiratory drive appears to be independent of the type of sleep; and 3) in wakefulness, the increase of the central inspiratory activity could be related to important excitatory inputs.     

Effect of resistive loads on pattern of respiratory muscle recruitment during exercise.

In healthy subjects, we compared the effects of an expiratory (ERL) and an inspiratory (IRL) resistive load (6 cmH2O.l-1.s) with no added resistive load on the pattern of respiratory muscle recruitment during exercise. Fifteen male subjects performed three exercise tests at 40% of maximum O2 uptake: 1) with no-added-resistive load (control), 2) with ERL, and 3) with IRL. In all subjects, we measured breathing pattern and mouth occlusion pressure (P0.1) from the 3rd min of exercise, in 10 subjects O2 uptake (VO2), CO2 output (VCO2), and respiratory exchange ratio (R), and in 5 subjects we measured gastric (Pga), pleural (Ppl), and transdiaphragmatic (Pdi) pressures. Both ERL and IRL induced a high increase of P0.1 and a decrease of minute ventilation. ERL induced a prolongation of expiratory time with a reduction of inspiratory time (TI), mean expiratory flow, and ratio of inspiratory to total time of the respiratory cycle (TI/TT). IRL induced a prolongation of TI with a decrease of mean inspiratory flow and an increase of tidal volume and TI/TT. With ERL, in two subjects, Pga increased and Ppl decreased more during inspiration than during control suggesting that the diaphragm was the most active muscle. In one subject, the increases of Ppl and Pga were weak; thus Pdi increased very little. In the two other subjects, Ppl decreased more during inspiration but Pga also decreased, leading to a decrease of Pdi. This suggests a recruitment of abdominal muscles during expiration and of accessory and intercostal muscles during inspiration. With IRL, in all subjects, Ppl again decreased more, Pga began to decrease until 40% of TI and then increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effort sensation, chemoresponsiveness, and breathing pattern during inspiratory resistive loading.

Although inspiratory resistive loading (IRL) reduces the ventilatory response to CO2 (VE/PCO2) and increases the sensation of inspiratory effort (IES), there are few data about the converse situation: whether CO2 responsiveness influences sustained load compensation and whether awareness of respiratory effort modifies this behavior. We studied 12 normal men during CO2 rebreathing while free breathing and with a 10-cmH2O.l-1.s IRL and compared these data with 5 min of resting breathing with and without the IRL. Breathing pattern, end-tidal PCO2, IES, and mouth occlusion pressure (P0.1) were recorded. Free-breathing VE/PCO2 was inversely related to an index of effort perception (IES/VE; r = -0.63, P less than 0.05), and the reduction in VE/PCO2 produced by IRL was related to the initial free-breathing VE/PCO2 (r = 0.87, P less than 0.01). IRL produced variable increases in inspiratory duration (TI), IES, and P0.1 at rest, and the change in tidal volume correlated with both VE/PCO2 (r = 0.63, P less than 0.05) and IES/VE (r = -0.69, P less than 0.05), this latter index also predicting the changes in TI with loading (r = -0.83, P less than 0.01). These data suggest that in normal subjects perception of inspiratory effort can modify free-breathing CO2 responsiveness and is as important as CO2 sensitivity in determining the response to short-term resistive loading. Individuals with good perception choose a small-tidal volume and short-TI breathing pattern during loading, possibly to minimize the discomfort of breathing.     

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.     

Mechanical impedance as determinant of inspiratory neural drive during exercise in humans

Five healthy males exercised progressively with small 2-min increments in work load. We measured inspiratory drive (occlusion pressure, P0.1), pulmonary resistance (RL), dynamic pulmonary compliance (Cdyn), transdiaphragmatic pressure (Pdi), and diaphragmatic electromyogram (EMGdi). Minute ventilation (VE), mean inspiratory flow rate (VT/TI), and P0.1 all increased exponentially with increased work load, but P0.1 increased at a faster rate than did VT/TI or VE. Thus effective impedance (P0.1/VT/TI) rose throughout exercise. The increasing P0.1 was mostly due to augmented Pdi and coincided with increased EMGdi during this initial portion of inspiration. We found no consistent change in RL or Cdyn throughout exercise. With He breathing (80% He-20% O2), RL was reduced at all work loads; P0.1 fell in comparison with air-breathing values and VE, VT, and VT/TI rose in moderate and heavy work; and P0.1/VT/TI was unchanged with increasing exercise loads. Step reductions in gas density at a constant work load of any intensity showed an immediate reduction in the rate of rise of EMGdi and Pdi followed by increased VT/TI, breathing frequency, and hypocapnia. These changes were maintained during prolonged periods of unloading and were immediately reversible on return to air breathing. These data are consistent with the existence of a reflex effect on the magnitude of inspiratory neural drive during exercise that is sensitive to the load presented by the normal mechanical time constant of the respiratory system. This "load" is a significant determinant of the hyperpneic response and thus of the maintenance of normocapnia during exercise.     

Breathing patterns during varied activities.

The level of ventilation attained and breathing patterns adopted during activity have important implications for the distribution and deposition of particles that are inhaled. However, breathing patterns and levels of ventilation adopted during specific physical activities are unknown. We used a noninvasive means of measuring ventilation in subjects performing a variety of activities (bicycling, arm ergometry, lifting, and pulling) during unencumbered (no mouthpiece) breathing and while breathing through a mouthpiece. Minute ventilation (VE), tidal volume (VT), inspiratory time (TI), and total breathing cycle time (TT) were measured initially both spirometrically and from body surface displacements. When a mouthpiece was used, VE and breathing patterns were significantly altered during all activities such that VE, VT, and TT increased by 16, 34, and 20%, respectively. This mouthpiece effect was attenuated at the higher levels of VE. A task dependency of breathing pattern was also noted such that there was much greater variability of VT and TI for a given VE during the lifting activity compared with bicycling (coefficient of variation for VT of 0.39 +/- 0.09 vs. 0.20 +/- 0.07, P less than 0.01; and for TI of 0.38 +/- 0.08 vs. 0.21 +/- 0.08, P less than 0.01). We conclude that a mouthpiece significantly alters breathing pattern during varied types and intensities of activities, and breathing patterns may differ significantly from one activity to another. When the total dose of particulates inhaled in the lung are assessed, the mouthpiece effect and activity effect on breathing pattern must be considered.     

Effects of acute hyperbaric oxygenation on respiratory control in cats

We studied ventilatory responsiveness to hypoxia and hypercapnia in anesthetized cats before and after exposure to 5 atmospheres absolute O2 for 90-135 min. The acute hyperbaric oxygenation (HBO) was terminated at the onset of slow labored breathing. Tracheal airflow, inspiratory (TI) and expiratory (TE) times, inspiratory tidal volume (VT), end-tidal PO2 and PCO2, and arterial blood pressure were recorded simultaneously before and after HBO. Steady-state ventilation (VI at three arterial PO2 (PaO2) levels of approximately 99, 67, and 47 Torr at a maintained arterial PCO2 (PaCO2, 28 Torr) was measured for the hypoxic response. Ventilation at three steady-state PaCO2 levels of approximately 27, 36, and 46 Torr during hyperoxia (PaO2 450 Torr) gave a hypercapnic response. Both chemical stimuli significantly stimulated VT, breathing frequency, and VI before and after HBO. VT, TI, and TE at a given stimulus were significantly greater after HBO without a significant change in VT/TI. The breathing pattern, however, was abnormal after HBO, often showing inspiratory apneusis. Bilateral vagotomy diminished apneusis and further prolonged TI and TE and increased VT. Thus a part of the respiratory effects of HBO is due to pulmonary mechanoreflex changes.     

Airway anesthesia effects on hypercapnic breathing pattern in humans

Minute ventilation (VE) and breathing pattern during an abrupt increase in fractional CO2 were compared in 10 normal subjects before and after airway anesthesia. Subjects breathed 7% CO2-93% O2 for 5 min before and after inhaling aerosolized lidocaine. As a result of airway anesthesia, VE and tidal volume (VT) were greater during hypercapnia, but there was no effect on inspiratory time (TI). Therefore, airway anesthesia produced an increase in mean inspiratory flow (VT/TI) during hypercapnia. The increase in VT/TI was compatible with an increase in neuromuscular output. There was no effect of airway anesthesia on the inspiratory timing ratio or the shape and position of the curve relating VT and TI. We also compared airway resistance (Raw), thoracic gas volume, forced vital capacity, forced expired volume at 1s, and maximum midexpiratory flow rate before and after airway anesthesia. A small (0.18 cmH2O X l-1 X s) decrease in Raw occurred after airway anesthesia that did not correlate with the effect of airway anesthesia on VT/TI. We conclude that airway receptors accessible to airway anesthesia play a role in hypercapnic VE.     

Background ventilatory stimulus as a determinant of load compensation

Compensation for inspiratory flow-resistive loading was compared during progressive hypercapnia and incremental exercise to determine the effect of changing the background ventilatory stimulus and to assess the influence of the interindividual variability of the unloaded CO2 response on evaluation of load compensation in normal subjects. During progressive hypercapnia, ventilatory response was incompletely defended with loading (mean unloaded delta VE/delta PCO2 = 3.02 +/- 2.29, loaded = 1.60 +/- 0.67 1.min-1.Torr-1 CO2, where VE is minute ventilation and PCO2 is CO2 partial pressure; P less than 0.01). Furthermore the degree of defense of ventilation with loading was inversely correlated with the magnitude of the unloaded CO2 response. During exercise, loading produced no depression in ventilatory response (mean delta VE/delta VCO2 unloaded = 20.5 +/- 1.9, loaded = 19.2 +/- 2.5 l.min-1.l-1.min-1 CO2 where VCO is CO2 production; P = NS), and no relationship was demonstrated between degree of defense of the exercise ventilatory response and the unloaded CO2 response. Differences in load compensation during CO2 rebreathing and exercise suggest the presence of independent ventilatory control mechanisms in these states. The type of background ventilatory stimulus should therefore be considered in load compensation assessment.     

Ventilatory response to fatiguing and nonfatiguing resistive loads in awake sheep

To study the changes in ventilation induced by inspiratory flow-resistive (IFR) loads, we applied moderate and severe IFR loads in chronically instrumented and awake sheep. We measured inspired minute ventilation (VI), ventilatory pattern [inspiratory time (TI), expiratory time (TE), respiratory cycle time (TT), tidal volume (VT), mean inspiratory flow (VT/TI), and respiratory duty cycle (TI/TT)], transdiaphragmatic pressure (Pdi), functional residual capacity (FRC), blood gas tensions, and recorded diaphragmatic electromyogram. With both moderate and severe loads, Pdi, TI, and TI/TT increased, TE, TT, VT, VT/TI, and VI decreased, and hypercapnia ensued. FRC did not change significantly with moderate loads but decreased by 30-40% with severe loads. With severe loads, arterial PCO2 (PaCO2) stabilized at approximately 60 Torr within 10-15 min and rose further to levels exceeding 80 Torr when Pdi dropped. This was associated with a lengthening in TE and a decrease in breathing frequency, VI, and TI/TT. We conclude that 1) timing and volume responses to IFR loads are not sufficient to prevent alveolar hypoventilation, 2) with severe loads the considerable increase in Pdi, TI/TT, and PaCO2 may reduce respiratory muscle endurance, and 3) the changes in ventilation associated with neuromuscular fatigue occur after the drop in Pdi. We believe that these ventilatory changes are dictated by the mechanical capability of the respiratory muscles or induced by a decrease in central neural output to these muscles or both.     

Breathing pattern in highly competitive cyclists during incremental exercise

The purpose of our investigation was to analyse the breathing patterns of professional cyclists during incremental exercise from submaximal to maximal intensities. A group of 11 elite amateur male road cyclists [E, mean age 23 (SD 2) years, peak oxygen uptake (VO2peak) 73.8 (SD 5.0) ml kg(-1) min(-1)] and 14 professional male road cyclists [P, mean age 26 (SD 2) years, (VO2peak) 73.2 (SD 6.6) ml kg(-1) min(-1)] participated in this study. Each of the subjects performed an exercise test on a cycle ergometer following a ramp protocol (exercise intensity increases of 25 W x min(-1)) until the subject was exhausted. For each subject, the following parameters were recorded during the tests: oxygen consumption (VO2), carbon dioxide output (VCO2), pulmonary ventilation (VE), tidal volume (VT), breathing frequency (fb), ventilatory equivalents for oxygen (VE x VO2(-1)) and carbon dioxide (VE x VCO2(-1)), end-tidal partial pressure of oxygen and partial pressure of carbon dioxide, inspiratory (tI) and expiratory (tE) times, inspiratory duty cycle (tI/tTOT, where tTOT is the time for one respiratory cycle), and mean inspiratory flow rate (VT/tI). Mean values of VE were significantly higher in E at 300, 350 and 400 W (P < 0.05, P < 0.05 and P < 0.01, respectively); fb was also higher in E in most moderate-to-maximal intensities. On the other hand, VT showed a different pattern in both groups at near-to maximal intensities, since no plateau was observed in P. The response of tI and tE was also different. Finally, VT/tI and tI/tTOT showed a similar response in both P and E. It was concluded that the breathing pattern of the two groups differed mainly in two aspects: in the professional cyclists, VE increased at any exercise intensity as a result of increases in both VT and fb, with no evidence of tachypnoeic shift, and tE was prolonged in this group at high exercise intensities. In contrast, neither the central drive nor the timing component of respiration seem to have been significantly altered by the training demands of professional cycling.     

Human breathing patterns on mouthpiece or face mask during air, CO2, or low O2

Steady-state breathing patterns on mouthpiece and noseclip (MP) and face mask (MASK) during air and chemostimulated breathing were obtained from pneumotachometer flow. On air, all 10 subjects decreased frequency (f) and increased tidal volume (VT) on MP relative to that on MASK without changing ventilation (VE), mean inspiratory flow (VT/TI), or mean expiratory flow (VT/TE). On elevated CO2 and low O2, MP exaggerated the increase in VE, f, and VT/TE due to profoundly shortened TE. On elevated CO2, MASK exaggerated VT increase with little change in f. Increased VE and VT/TI were thus due to increased VT. During low O2 on MASK, both VT and f increased. During isocapnia, shortened TE accounted for increased f; during hypocapnia, increased f was related primarily to shortened TI. Thus the choice of a mouthpiece or face mask differentially alters breathing pattern on air and all components of ventilatory responses to chemostimuli. In addition, breathing apparatus effects are not a simple consequence of a shift from oronasal to oral breathing, since a noseclip under the mask did not change breathing pattern from that on mask alone.     

Effect of aging on ventilatory response to exercise and CO2

Studies were performed to determine the effects of aging on the ventilatory responsiveness to two known respiratory stimulants, inhaled CO2 and exercise. Although explanation of the physiological mechanisms underlying development of exercise hyperpnea remains elusive, there is much circumstantial evidence that during exercise, however mediated, ventilation is coupled to CO2 production. Thus matched groups of young and elderly subjects were studied to determine the relationship between increasing ventilation and increasing CO2 production (VCO2) during steady-state exercise and the change in their minute ventilation in response to progressive hypercapnia during CO2 rebreathing. We found that the slope of the ventilatory response to hypercapnia was depressed in elderly subjects when compared with the younger control group (delta VE/delta PCO2 = 1.64 +/- 0.21 vs. 2.44 +/- 0.40 l X min-1 X mmHg-1, means +/- SE, respectively). In contrast, the slope of the relationship between ventilation and CO2 production during exercise in the elderly was greater than that of younger subjects (delta VE/delta VCO2 = 29.7 +/- 1.19 vs. 25.3 +/- 1.54, means +/- SE, respectively), as was minute ventilation at a single work load (50 W) (32.4 +/- 2.3 vs. 25.7 +/- 1.54 l/min, means +/- SE, respectively). This increased ventilation during exercise in the elderly was not produced by arterial O2 desaturation, and increased anaerobiasis did not play a role. Instead, the increased ventilation during exercise seems to compensate for increased inefficiency of gas exchange such that exercise remains essentially isocapnic. In conclusion, in the elderly the ventilatory response to hypercapnia is less than in young subjects, whereas the ventilatory response to exercise is greater.     

Effect of elastic loading on ventilatory pattern during progressive exercise

Ventilatory responses to progressive exercise, with and without an inspiratory elastic load (14.0 cmH2O/l), were measured in eight healthy subjects. Mean values for unloaded ventilatory responses were 24.41 +/- 1.35 (SE) l/l CO2 and 22.17 +/- 1.07 l/l O2 and for loaded responses were 24.15 +/- 1.93 l/l CO2 and 20.41 +/- 1.66 l/l O2 (P greater than 0.10, loaded vs. unloaded). At levels of exercise up to 80% of maximum O2 consumption (VO2max), minute ventilation (VE) during inspiratory elastic loading was associated with smaller tidal volume (mean change = 0.74 +/- 0.06 ml; P less than 0.05) and higher breathing frequency (mean increase = 10.2 +/- 0.98 breaths/min; P less than 0.05). At levels of exercise greater than 80% of VO2max and at exhaustion, VE was decreased significantly by the elastic load (P less than 0.05). Increases in respiratory rate at these levels of exercise were inadequate to maintain VE at control levels. The reduction in VE at exhaustion was accompanied by significant decreases in O2 consumption and CO2 production. The changes in ventilatory pattern during extrinsic elastic loading support the notion that, in patients with fibrotic lung disease, mechanical factors may play a role in determining ventilatory pattern.     

Dose effect of caffeine on control of breathing and respiratory response to CO2 in cats

The dose effect of caffeine (10-70 mg/kg iv) on pulmonary ventilation (VE), mean inspiratory flow (VT/TI), and tracheal pressure generated 0.3 and 0.5 s (P0.3 and P0.5, respectively) after the onset of inspiration against airway occluded at end expiration was studied in cats anesthetized with pentobarbital sodium (35 mg/kg ip) breathing various gas mixtures. With air and 50% O2 (balance N2), increasing doses of caffeine caused a progressive increase in VE that was associated with a reduction in end-tidal PCO2. When the latter was maintained at control (precaffeine) level by inhalation of CO2, the increase in VE was, at all caffeine levels, about three times that under nonisocapnic conditions. Both under isocapnic and nonisocapnic conditions the greatest incremental changes of VE were observed after administration of the first 10-mg/kg aliquot of caffeine, i.e., the current acceptable clinical dose. In all instances, the changes in VE were proportionally the same as the corresponding changes in VT/TI, P0.3, and P0.5, suggesting that caffeine did not appreciably alter either the shape of the inspiratory driving pressure waveform or the impedance of the respiratory system but simply acted by increasing the amplitude of the neuromuscular inspiratory output. An additive interaction between caffeine and end-tidal PCO2 was observed in the VE, VT/TI, and P0.3 responses at levels of CO2 at or below the eucapnic range.