Changes in lung volume and breathing pattern during exercise and CO2 inhalation in humans

Lung volume changes during CO2 inhalation and exercise were compared in seven human subjects. Expiratory reserve volume (ERV) normalized by vital capacity (VC) was used as an index of end-expiratory lung volume (EELV). Work loads tried were 30, 60, and 90 W and inspired CO2 concentrations were 3.5 and 5.0%. Exercise at 30 W led to a significant decrease in EELV, by 7% VC (P less than 0.005), with no further change at higher levels of exercise (P greater than 0.1). Both 3.5 and 5.0% CO2 inhalation resulted in an increase in EELV that was not statistically significant (3% VC, P greater than 0.1). A possible linkage of this different EELV behavior to breathing pattern was tested. The tidal volume-inspiratory duration curve shifted to a higher volume region during exercise compared with CO2 inhalation. Consequently, the volume-time threshold characteristic was better described by an end-inspiratory lung volume-inspiratory duration plot, resulting in a common relationship under these two different stimuli. These results suggest that the depth and rate of breathing in humans can be affected by not only phasic but also tonic components. A decrease in functional residual capacity or EELV was peculiar to exercise and should be associated with increased mechanical efficiency compared with CO2 inhalation. Theoretical predictions based on work of breathing optimization via a decreased EELV seemed to be capable of explaining isocapnic exercise hyperpnea in conjunction with proportional control of arterial CO2 tension.     

Early dynamics of O2 uptake and heart rate as affected by exercise work rate

The kinetics of O2 uptake (Vo2) and heart rate (HR) in response to constant work rate exercise have been characterized as two phases, an immediate response as the result largely of abrupt hemodynamic changes and a slower response as the result of increases in both blood flow and arteriovenous O2 difference (avDo2). There are few data reported concerning Vo2 and HR during phase I or the relationship between their kinetics and work rate or intensity. Because phase I responses depend on abrupt cardiovascular adjustments, it was hypothesized that phase I increases in Vo2 and HR would be greater the more "fit" the subject and would be relatively independent of work rate. To test this, 10 normal subjects exercised from rest to each of five work rates ranging from unloaded cycling to 150 W. The phase I increases of Vo2, HR, and Vo2/HR had small but significant correlations with work rate but not with fitness. At very low work rates (unloaded cycling and 25 W), Vo2 and HR often exceeded their steady-state levels in phase I. There was therefore no phase II increase for Vo2 or HR at these work rates, the entire O2 requirement having been met by phase I circulatory adjustments. For all other work rates, mean response times for Vo2 and HR were related to fitness and were slower than those for Vo2/HR, suggesting that avDo2 reached a steady state before cardiac output did.     

Effect of bronchomotor tone on work rate of breathing

We studied the optimal airway caliber for minimizing the work rate of breathing in the lung (W) with different bronchomotor tones in six normal subjects. The inhalation of methacholine contracted airway smooth muscle, and the inhalation of salbutamol relaxed it. To calculate W at a given alveolar ventilation (VA), anatomical dead space (VDanat), pulmonary resistance (RL), and dynamic compliance were measured simultaneously, breath by breath, during various breathing maneuvers. VDanat increased and RL decreased with both increased breathing frequency and tidal volume, even at a given airway tone. This suggests that the airway caliber varied even at a given bronchomotor tone. The minimum W at a given VA increased in constricted airways, but there was no significant difference between control airways after saline inhalation and relaxed airways. It has been suggested that airway smooth muscle tones at both control and relaxed conditions bring W to a minimum and that the airway smooth muscle tone existing in the control state acts to keep the airway caliber optimal in order to minimize the W and stabilize the airway mechanics.     

Muscular efficiency during steady-rate exercise: effects of speed and work rate.

In a comparison of traditional and theoretical exercise efficiency calculations male subjects were studied during steady-rate cycle ergometer exercises of "0," 200, 400, 600, and 800 kgm/min while pedaling at 40, 60, 80, and 100 rpm. Gross (no base-line correction), net (resting metabolism as base-line correction), work (unloading cycling as base-line correction), and delta (measurable work rate as base-line correction) efficiencies were computed. The result that gross (range 7.5-20.4%) and net (9.8-24.1%) efficiencies increased with increments in work rate was considered to be an artifact of calculation. A LINEAR OR SLIGHTLY EXPONENTIAL RELATIONSHIP BETWEEN CALORIC OUTPUT AND WORK RATE DICTATES EITHER CONSTANT OR DECREASING EFFICIENCY WITH INCREMENTS IN WORK. The delta efficiency (24.4-34.0%) definition produced this result. Due to the difficulty in obtaining 0 work equivalents, the work efficiency definition proved difficult to apply. All definitions yielded the result of decreasing efficiency with increments in speed. Since the theoretical-thermodynamic computation (assuming mitochondrial P/O = 3.0 and delta G = -11.0 kcal/mol for ATP) holds only for CHO, the traditional mode of computation (based upon VO2 and R) was judged to be superior since R less than 1.0. Assuming a constant phosphorylative-coupling efficiency of 60%, the mechanical contraction-coupling efficiency appears to vary between 41 and 57%.     

O2 Uptake in hyperthyroidism during constant work rate and incremental exercise

To investigate the effect of hyperthyroidism on the pattern and time course of O2 uptake (VO2) following the transition from rest to exercise, six patients and six healthy subjects performed cycle exercise at an average work rate (WR) of 18 and 20 W respectively. Cardiorespiratory variables were measured breath-by-breath. The patients also performed a progressively increasing WR test (1-min increments) to the limit of tolerance. Two patients repeated the studies when euthyroid. Resting and exercise steady-state (SS) VO2 (ml.kg-1.min-1) were higher in the patients than control (5.8, SD 0.9 vs 4.0, SD 0.3 and 12.1, SD 1.5 vs 10.2, SD 1.0 respectively). The increase in VO2 during the first 20 s exercise (phase I) was lower in the patients (mean 89 ml.min-1, SD 30) compared to the control (265 ml.min-1, SD 90), while the difference in half time of the subsequent (phase II) increase to the SS VO2 (patient 26 s, SD 8; controls 17 s, SD 8) were not significant (P = 0.06). The O2 cost per WR increment (delta VO2/delta WR) in ml.min-1.w-1, measured during the incremental period (mean 10.9; range 8.3-12.2), was always within two standard deviations of the normal value (10.3, SD 1). In the two patients who repeated the tests, both the increment of VO2 from rest to SS during constant WR exercise and the delta VO2/delta WRs during the progressive exercise were higher in the hyperthyroid state than during the euthyroid state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pressure-time product, work rate, and endurance during resistive breathing in humans

We examined the effect of increasing work rate, without a corresponding increase in the pressure-time product, on energy cost and inspiratory muscle endurance (Tlim) in five normal subjects during inspiratory resistive breathing. Tidal volume, mean inspiratory mouth pressure, duty cycle, and hence the pressure-time product were kept constant, whereas work rate was varied by changing the frequency of breathing. There was a linear decrease in Tlim of -2.1 +/- 0.5 s.J-1.min-1 (r = 0.87 +/- 0.06) with increasing work rate. The data satisfied a model of energy balance during fatiguing runs (Monod and Scherrer. Ergonomics 8: 329-337, 1965) and were consistent with the hypothesis that the rate of energy supply, or respiratory muscle blood flow, is fixed when the pressure-time product is constant. Our results indicate that during inspiratory resistive breathing against fatiguing loads, work rate determines endurance independently of the pressure-time product. On the basis of the model, our results lead to estimates of respiratory muscle blood flow and available energy stores under the conditions of our experiment.     

Ventilatory response to exercise in aged runners breathing He-O2 or inspired CO2.

The ventilatory response to exercise below ventilatory threshold (VTh) increases with aging, whereas above VTh the ventilatory response declines only slightly. We wondered whether this same ventilatory response would be observed in older runners. We also wondered whether their ventilatory response to exercise while breathing He-O(2) or inspired CO(2) would be different. To investigate, we studied 12 seniors (63 +/- 4 yr; 10 men, 2 women) who exercised regularly (5 +/- 1 days/wk, 29 +/- 11 mi/wk, 16 +/- 6 yr). Each subject performed graded cycle ergometry to exhaustion on 3 separate days, breathing either room air, 3% inspired CO(2), or a heliox mixture (79% He and 21% O(2)). The ventilatory response to exercise below VTh was 0.35 +/- 0.06 l x min(-1) x W(-1) and above VTh was 0.66 +/- 0.10 l x min(-1) x W(-1). He-O(2) breathing increased (P < 0.05) the ventilatory response to exercise both below (0.40 +/- 0.12 l x min(-1) x W(-1)) and above VTh (0.81 +/- 0.10 l x min(-1) x W(-1)). Inspired CO(2) increased (P < 0.001) the ventilatory response to exercise only below VTh (0.44 +/- 0.10 l x min(-1) x W(-1)). The ventilatory responses to exercise with room air, He-O(2), and CO(2) breathing of these fit runners were similar to those observed earlier in older sedentary individuals. These data suggest that the ventilatory response to exercise of these senior runners is adequate to support their greater exercise capacity and that exercise training does not alter the ventilatory response to exercise with He-O(2) or inspired CO(2) breathing.     

Luft's syndrome: O2 cost of exercise and chemical control of breathing.

The oxygen cost of exercise and chemical control of breathing were studied in a subject with Luft's syndrome, a disorder in which skeletal muscle mitochondria have a high "resting" O2 consumption which is imcreased only slightly by stimulation with excess phosphate acceptor, but a normal P/O ratio. The O2 consumption was more than three times normal (1.05 1/min) at rest but could be doubled when stimulated by maximal exercise. The O2 cost of exercise was similar to that of normal subjects. At rest, arterial blood PCO2 and ventilatory response to CO2 were normal, while ventilatory response to hypoxia was four times the predicted value. The data 1) confirm, in vivo, the normal respiratory efficiency of skeletal muscles in this disorder; 2) suggest that in vitro estimates of the extent to which mitochondrial respiration can be stimulated may not correlate with in vivo determinations; and 3) suggests that hypermetabolism per se can cause the ventilatory adjustments which are associated with exercise in normal subjects.     

Individuality of breathing patterns during hypoxia and exercise.

Breathing was recorded via a pulsed ultrasonic flowmeter in 11 healthy subjects, at rest and during steady-state exercise (at 50% of their maximal O2 consumption) at both sea level (200 m) and simulated altitude (4,500 m in a hypobaric chamber). The pattern of breathing was quantified breath by breath in terms of classical respiratory variables (tidal volume and inspiratory and expiratory times), and the shape of the entire airflow profile was quantified by harmonic analysis. Statistical tests were used to compare the within-individual with the between-individual variations. In comparing the sea level vs. altitude rest (16% increase in ventilation) and sea level vs. altitude exercise (40% increase in ventilation) airflow profiles, we found a significantly greater resemblance within the individual than between individuals. Comparisons of sea level rest and exercise (295% increase in ventilation) and altitude rest and exercise (375% increase in ventilation) revealed no similarity within individuals. Despite airflow profile changes between rest and exercise, it is still possible to attest to a diversity of flow profile between individuals during exercise. Hypoxia at rest or during exercise does not alter the phenomenon of the individuality of breathing patterns.     

Nasal resistance and flow resistive work of nasal breathing during exercise: effects of a nasal dilator strip.

Using posterior rhinomanometry, we measured nasal airflow resistance (Rn) and flow-resistive work of nasal breathing (WONB), with an external nasal dilator strip (ENDS) and without (control), in 15 healthy adults (6 men, 9 women) during exclusive nasal breathing and graded (50-230 W) exercise on a cycle ergometer. ENDS decreased resting inspiratory and/or expiratory Rn (at 0.4 l/s) by >0.5 cmH(2)O. l(-1). s in 11 subjects ("responders"). Inspired ventilation (VI) increased with external work rate, but tended to be greater with ENDS. Inspiratory and expiratory Rn (at 0.4 l/s) decreased as VI increased but, in responders, tended to remain lower with ENDS. Inspiratory (but not expiratory) Rn at peak nasal airflow (Vn) increased as VI increased but, again, was lower with ENDS. At a VI of approximately 35 l/min, ENDS decreased flow limitation and hysteresis of the inspiratory transnasal pressure-flow curve. In responders, ENDS reduced inspiratory WONB per breath and inspiratory nasal power values during exercise. We conclude that ENDS stiffens the lateral nasal vestibule walls and, in responders, may reduce the energy required for nasal ventilation during exercise.     

Muscle fiber recruitment and the slow component of O2 uptake: constant work rate vs. all-out sprint exercise

The slow component of pulmonary O(2) uptake (Vo(2)) during constant work rate (CWR) high-intensity exercise has been attributed to the progressive recruitment of (type II) muscle fibers. We tested the following hypotheses: 1) the Vo(2) slow component gain would be greater in a 3-min all-out cycle test than in a work-matched CWR test, and 2) the all-out test would be associated with a progressive decline, and the CWR test with a progressive increase, in muscle activation, as estimated from the electromyogram (EMG) of the vastus lateralis muscle. Eight men (aged 21-39 yr) completed a ramp incremental test, a 3-min all-out test, and a work- and time-matched CWR test to exhaustion. The maximum Vo(2) attained in an initial ramp incremental test (3.97 ± 0.83 l/min) was reached in both experimental tests (3.99 ± 0.84 and 4.03 ± 0.76 l/min for all-out and CWR, respectively). The Vo(2) slow component was greater (P < 0.05) in the all-out test (1.21 ± 0.31 l/min, 4.2 ± 2.2 ml·min(-1)·W(-1)) than in the CWR test (0.59 ± 0.22 l/min, 1.70 ± 0.5 ml·min(-1)·W(-1)). The integrated EMG declined by 26% (P < 0.001) during the all-out test and increased by 60% (P < 0.05) during the CWR test from the first 30 s to the last 30 s of exercise. The considerable reduction in muscle efficiency in the all-out test in the face of a progressively falling integrated EMG indicates that progressive fiber recruitment is not requisite for development of the Vo(2) slow component during voluntary exercise in humans.     

Muscle kinematics for minimal work of breathing.

A mathematical model was analyzed to obtain a quantitative and testable representation of the long-standing hypothesis that the respiratory muscles drive the chest wall along the trajectory for which the work of breathing is minimal. The respiratory system was modeled as a linear elastic system that can be expanded either by pressure applied at the airway opening (passive inflation) or by active forces in respiratory muscles (active inflation). The work of active expansion was calculated, and the distribution of muscle forces that produces a given lung expansion with minimal work was computed. The calculated expression for muscle force is complicated, but the corresponding kinematics of muscle shortening is simple: active inspiratory muscles shorten more during active inflation than during passive inflation, and the ratio of active to passive shortening is the same for all active muscles. In addition, the ratio of the minimal work done by respiratory muscles during active inflation to work required for passive inflation is the same as the ratio of active to passive muscle shortening. The minimal-work hypothesis was tested by measurement of the passive and active shortening of the internal intercostal muscles in the parasternal region of two interspaces in five supine anesthetized dogs. Fractional changes in muscle length were measured by sonomicrometry during passive inflation, during quiet breathing, and during forceful inspiratory efforts against a closed airway. Active muscle shortening during quiet breathing was, on average, 70% greater than passive shortening, but it was only weakly correlated with passive shortening. Active shortening inferred from the data for more forceful inspiratory efforts was approximately 40% greater than passive shortening and was highly correlated with passive shortening. These data support the hypothesis that, during forceful inspiratory efforts, muscle activation is coordinated so as to expand the chest wall with minimal work.     

Effect of hilar nerve denervation on breathing and arterial PCO2 during CO2 inhalation

We determined the effects of denervating the hilar branches (HND) of the vagus nerves on breathing and arterial PCO2 (PaCO2) in awake ponies during eupnea and when inspired PCO2 (PICO2) was increased to 14, 28, and 42 Torr. In five carotid chemoreceptor-intact ponies, breathing frequency (f) was less, whereas tidal volume (VT), inspiratory time (TI), and ratio of TI to total cycle time (TT) were greater 2-4 wk after HND than before HND. HND per se did not significantly affect PaCO2 at any level of PICO2, and the minute ventilation (VE)-PaCO2 response curve was not significantly altered by HND. Finally, the attenuation of a thermal tachypnea by elevated PICO2 was not altered by HND. Accordingly, in carotid chemoreceptor-intact ponies, the only HND effect on breathing was the change in pattern classically observed with attenuated lung volume feedback. There was no evidence suggestive of a PCO2-H+ sensory mechanism influencing VE, f, VT, or PaCO2. In ponies that had the carotid chemoreceptors denervated (CBD) 3 yr earlier, HND also decreased f, increased VT, TI, and TT, but did not alter the slope of the VE-PaCO2 response curve. However, at all levels of elevated PICO2, the arterial hypercapnia that had persistently been attenuated, since CBD was restored to normal by HND. The data suggest that during CO2 inhalation in CBD ponies a hilar-innervated mechanism influences PaCO2 by reducing physiological dead space to increase alveolar ventilation.