Ventilatory Response To Exercise Research Articles

A review of the control of breathing during exercise

During the past 100 years many experimental investigations have been carried out in an attempt to determine the control mechanisms responsible for generating the respiratory responses observed during incremental and constant-load exercise tests. As a result of these investigations a number of different and contradictory control mechanisms have been proposed to be the sole mediators of exercise hyperpnea. However, it is now becoming evident that none of the proposed mechanisms are solely responsible for eliciting the exercise respiratory response. The present-day challenge appears to be one of synthesizing the proposed mechanisms, in order to determine the role that each mechanism has in controlling ventilation during exercise. This review, which has been divided into three primary sections, has been designed to meet this challenge. The aim of the first section is to describe the changes in respiration that occur during constant-load and incremental exercise. The second section briefly introduces the reader to traditional and contemporary control mechanisms that might be responsible for eliciting at least a portion of the exercise ventilatory response during these types of exercise. The third section describes how the traditional and contemporary control mechanisms may interact in a complex fashion to produce the changes in breathing associated with constant-load exercise, and incorporates recent experimental evidence from our laboratory.

Hypoxic exercise does not elicit long-term modulation of the normoxic exercise ventilatory response in Goats.

Ventilation typically increases during exercise to an extent whereby PaCO2 is maintained at or below resting levels (4).Traditionally, attempts to describe the neural mechanisms responsible for the exercise hyperpnoea have invoked a combination of feed-forward and feedback signals (5,8).

Long-term modulation of the exercise ventilatory response in goats.

1. To test the hypothesis that repeated associations of exercise and increased respiratory dead space elicit mechanisms that augment future ventilatory responses to exercise alone, experiments were conducted on normal adult goats familiarized with experimental procedures. 2. Measurements of ventilation, arterial blood gases and CO2 production were made at rest, during mild steady-state exercise (4 km h-1; 5% grade) and with increased dead space at rest in seven goats before and after training. In Series I experiments, training consisted of fourteen to twenty exercise trials explicitly paired with increased dead space (0.8 l) over 2 days. Increased dead space predominantly represents a CO2 chemoreceptor stimulus with only mild hypoxic stimulation. Post-training measurements were made 1-6 h and 1 week after training was completed. 3. The same goats repeated a slightly modified protocol several months later (Series II; 6 trials per day for 4 days) to determine if responses were both repeatable and reversible, and to investigate training effects on dynamic ventilatory responses at the onset of exercise. 4. In Series I experiments, resting minute ventilation and breathing frequency were elevated 1-6 h post-training compared to baseline (44 and 74% respectively), whereas resting tidal volume decreased (14%). One week post-training, resting values had returned to baseline. Series II training had no significant effects on resting measurements. 5. Relative to baseline, arterial partial pressure of CO2 (Pa,CO2) values decreased significantly more from rest to exercise 1-6 h post-training in both Series I (2.7 +/- 0.2 vs. 1.8 +/- 0.9 mmHg) and Series II (3.4 +/- 0.6 vs. 2.0 +/- 0.6 mmHg). The exercise ventilatory response increased 25-28% 1-6 h post-training (both series), largely due to a greater exercise frequency response, but returned to baseline 1 week post-training. Training had no effect on ventilatory responses to CO2 at rest, suggesting that decreases in CO2 chemoreceptor responsiveness did not cause the greater exercise ventilatory response. Model estimates indicate that the net feedforward exercise ventilatory stimulus was increased 40-50% by training. 6. Training had no discernable effects on ventilatory dynamics at the onset of exercise. However, post-training differences in Pa,CO2 regulation and ventilation were established early in exercise, prior to steady state. 7. Collectively, these experiments suggest a previously unsuspected degree of repeatable and reversible plasticity in the control system subserving the exercise ventilatory response. Such plasticity may contribute to the development of normal exercise hyperpnoea and to adaptive responses of the ventilatory control system in adult animals.

Exercise ventilatory response to upright and aero-posture cycling

The aero-cycling posture has become increasingly popular among cyclists. Because of the potential for altered lung mechanics in the aero-cycling posture, the ventilatory and gas exchange profiles of 10 moderately trained males (31.1 +/- 6.3 yr, mean +/- SD) exercising on a cycle ergometer in the upright posture (UC) and aero-cycling (AC) posture were studied. Exercise consisted of 3-min work stages with 50-W incremental changes until volitional exhaustion. Ventilatory and gas exchange responses to exercise were averaged each minute. Maximal oxygen consumption (54.3 +/- 6.3 vs 53.4 +/- 6.9 ml.kg-1.min-1) in the UC and AC were not significantly different. Maximal values for ventilation (132.5 +/- 32.3 vs 128.0 +/- 28.7 l.min-1), tidal volume (2.7 +/- 0.5 vs 2.6 +/- 0.3 1.br-1), breathing frequency (50.0 +/- 8.0 vs 47.0 +/- 5.0 br.min-1), and submaximal ventilatory and heart rate responses in the UC were not significantly different compared with the AC. No significant difference existed between postures for mean inspiratory flow and inspiratory duty cycle at comparable submaximal power outputs. These results indicate that at absolute power outputs, ventilatory responses, as determined by respiratory pattern and timing, and metabolic cost, were similar in the UC and AC. Thus, the AC does not impair physiologic responses to high intensity exercise.

Serotonin is necessary for short-term modulation of the exercise ventilatory response

The exercise ventilatory response is augmented during conditios of increased respiratory dead space (ΔVd), a phenomenon that we refer to as short term modulation (STM). To test the hypothesis that serotonin is necessary in the mechanims underlying STM, experiments were conducted on ten awake goats. Ventilation, CO 2 production and Pa CO 2 were measured at rest and during treadmill exercise (4 km/h, 5% grade), with and without ΔVd (0.25 L), before and after systemic administration of the serotonin receptor antagonist, methysergide maleate ( n=6; 1 mg/kg, i.v), or the tryptophan hydroxylase inhibitor, p-chlorophenylalanine (PCPA; n = 4; 100 mg/kg, i.v.). Pre-methysergide: (1) Pa CO 2 decreased from rest to exercise to similar degree with (−1.9mmHg) and without (−1.8mmHg) ΔVd; (2) the exercise ventilatory response increased 59%±13% ( p<0.01) with ΔVd, accounting for similar exercise Pa CO 2 regulation and demonstrating STM; and (3) effects of ΔVd on exercise tidal volume and frequency responses were inconsistent. Post-methysergide: (1) there were no significant effects on ventilation or Pa CO 2 at rest or during exercise in control (mask) conditions; (2) the exercise ventilatory response was unaffected by ΔVd, thereby allowing Pa CO 2 to increase 4.1±3.0 mmHg from the rest to exercise ( P<0.05); and (3) with ΔVd during exercise, the tidal volume response was increased, but was offset by a decreased frequency response. Following PCPA (16–24 h): (1) hyperventilation was evident at rest and during exercise; (2) the exercise ventilatory response was augmented, indicating STM; and (3) the exercise ventilatory response with ΔVd was not affected further, allowing Pa CO 2 to increase form rest to exercise and indicating an inability to elicit further STM. These data suggest that serotonin is necessary for short term modulation of the exercise ventilatory response with increased respiratory dead space, although the location of relevant serotonin receptors is not yet clear.

Potentiation of exercise ventilatory response by airway CO2 and dead space loading.

We examined the effects of different modes of airway CO2 load on the ventilation-CO2 output (VE-VCO2) relationship during mild to moderate exercise. Four young and three older male subjects underwent incremental steady-state treadmill exercise while breathing a mixture of CO2 in O2 (CO2 loading) or 100% O2 with and without a large external dead space [DS loading and control (C), respectively]. During DS loading, the elevated arterial PCO2 (PaCO2) remained constant from rest to mild exercise and began to increase only at higher work rates. To achieve similar chemical drive, the same PaCO2 levels were established during CO2 loading by external PCO2 forcing. In the young group, CO2 loading resulted in a steepening of the VE-VCO2 relationship compared with C, whereas in the older group the reverse pattern was found. DS loading resulted in a consistent increase in the VE-VCO2 slope compared with C and CO2 loading [39.1 +/- 5.6 (mean +/- SD) vs. 24.9 +/- 5.0 and 26.7 +/- 4.4, respectively] in all subjects. The difference in potentiation of VE-VCO2 by CO2 and DS loading was not due to differences in mean chemical drive or changes in breathing pattern. Thus changes in the profile of airway CO2 influx may have an independent influence on ventilatory CO2-exercise interaction. Peripheral chemoreceptors mediation, although important, is not obligatory for this behavior.

Ventilation and Gas Exchange during Exercise in Sickle Cell Anemia

Adults with sickle cell anemia (SCA) have restrictive lung impairment, increased alveolar dead space, and hypoxemia. These factors, together with increased anaerobic metabolism, are thought to cause exercise hyperventilation. To assess the role of each of these in children, 34 patients with SCA and 16 control subjects performed pulmonary function and exercise tests. Twenty-eight patients with SCA had spirometric values and lung volumes, and all but two patients with SCA had arterial saturation greater than 91% during exercise. Despite a low VO2max (30.07 +/- 6.55 ml/min/kg), the ventilatory anaerobic threshold (VAT) in the patients occurred at a similar %VO2max as in the control subjects (69 +/- 9% versus 63 +/- 12%). The slope of the delta VE/delta VCO2 relationship for sub-VAT work was steeper in the patients (29.4 +/- 6.5 versus 24.7 +/- 5.2, p = 0.01), and the ventilatory equivalent for CO2 (VE/VCO2) in steady-state exercise was greater in the patients than in the control subjects (33.2 +/- 3.5 versus 30.8 +/- 3.5, p = 0.03). End-tidal PCO2 did not differ (38.3 +/- 3.0 versus 39.2 +/- 3.1), indicating equivalent alveolar ventilation. The patients had a higher dead space:tidal volume ratio (VD/VT) than did the control subjects (0.204 +/- 0.033 versus 0.173 +/- 0.024, p = 0.0005). The PaCO2 was significantly lower in those with lower Hb, but there was no difference in pH. In conclusion, children with SCA have an increased exercise ventilatory response caused in part by increased physiologic dead space, and in part by their low Hb. The greater dead space may be the result of sickle cells impairing capillary perfusion to ventilated alveoli.

Single Lung Transplantation for Primary Pulmonary Hypertension

Single lung transplantation has become a therapeutic option for end-stage interstitial lung disease and obstructive lung disease. Our group recently extended this treatment to three patients with primary pulmonary hypertension. All patients had marked decreases in pulmonary artery pressures and pulmonary vascular resistance and increases in cardiac output following single lung transplantation. Spirometry, lung volumes, and diffusion capacity were not different in comparison to preoperative studies. Quantitative ventilation-perfusion scans revealed the majority of perfusion distributed to the transplanted lung, with ventilation approximately equally divided between the native and the transplanted lung. Despite ventilation-perfusion imbalance, there was no resting hypoxemia and there was no arterial oxygen desaturation with exercise. One patient expired on the 30th postoperative day due to cytomegalovirus infection of the lungs. In the remaining two patients, maximum exercise capacity following transplantation was near normal in one recipient and reduced in the second recipient. Of note, there was no evidence of ventilatory limitation or impaired oxygenation during exercise in these two recipients. Although an exaggerated exercise ventilatory response was present, this did not limit exercise performance. This report supports the use of single lung transplantation for the treatment of primary pulmonary hypertension.

Ventilatory control during exercise with increased respiratory dead space in goats

Our objectives were to determine 1) the effects of increased respiratory dead space (VD) on the ventilatory response to exercise and 2) whether changes in the ventilatory response are due to changes in chemoreceptor feedback (rest to exercise) vs. changes in the feedforward exercise stimulus. Steady-state ventilation (VI) and arterial blood gas responses to mild or moderate hyperoxic exercise in goats were compared with and without increased VD. Responses were compared using a simple mathematical model with the following assumptions: 1) steady state, 2) linear CO2 chemoreceptor feedback, 3) linear feedforward exercise stimulus proportional to CO2 production (VCO2) and characterized by an exercise gain (Gex), and 4) additive exercise stimulus and CO2 feedback producing the system gain (Gsys = delta VI/delta VCO2). Model predictions at constant Gex [assuming VD-to-tidal volume (VT) ratio independent of VCO2] are that increased VD/VT will 1) increase arterial PCO2 (PaCO2) and VI at rest and 2) increase Gsys via changes in chemoreceptor feedback due to a small increase in the PaCO2 vs. VCO2 slope. Experimental results indicate that increased VD increased VD/VT, PaCO2, and VI at rest and increased Gsys during exercise. However, measurable changes in the PaCO2 vs. VCO2 slope occurred only at high VD/VT or running speeds. Gex was estimated at each VD for each goat by using the model in conjunction with experimental measurements. With 0.2 liter VD, Gex increased 40% (P less than 0.01); with 0.6 liter VD, Gex increased 110% between 0 and 2.4 km/h and 5% grade (P less than 0.01) but not between 2.4 and 4.8 km/h. Thus, Gex is increased by VD through a limited range. In goats, increases in Gsys with increased VD result from increases in both Gex and CO2 chemoreceptor feedback. These results are consistent with other experimental treatments that increase the exercise ventilatory response, maintaining constant relative PaCO2 regulation, and suggest that a common mechanism linked to resting ventilatory drive modulates Gex.

Exercise and recovery ventilatory and VO2 responses of patients with McArdle's disease

This study was designed to determine whether patients with McArdle's disease, who do not increase their blood lactate levels during and after maximal exercise, have a slow "lactacid" component to their recovery O2 consumption (VO2) response after high-intensity exercise. VO2 was measured breath by breath during 6 min of rest before exercise, a progressive maximal cycle ergometer test, and 15 min of recovery in five McArdle's patients, six age-matched control subjects, and six maximal O2 consumption- (VO2 max) matched control subjects. The McArdle's patients' ventilatory threshold occurred at the same relative exercise intensity [71 +/- 7% (SD) VO2max] as in the control groups (60 +/- 13 and 70 +/- 10% VO2max) despite no increase and a 20% decrease in the McArdle's patients' arterialized blood lactate and H+ levels, respectively. The recovery VO2 responses of all three groups were better fit by a two-, than a one-, component exponential model, and the parameters of the slow component of the recovery VO2 response were the same in the three groups. The presence of the same slow component of the recovery VO2 response in the McArdle's patients and the control subjects, despite the lack of an increase in blood lactate or H+ levels during maximal exercise and recovery in the patients, provides evidence that this portion of the recovery VO2 response is not the result of a lactacid mechanism. In addition, it appears that the hyperventilation that accompanies high-intensity exercise may be the result of some mechanism other than acidosis or lung CO2 flux.

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.

Acute altitude exposure and altered acid-base states. I. Effects on the exercise ventilation and blood lactate responses.

This study examined the influence of acute altitude (AL) exposure alone or in combination with metabolic acid-base manipulations on the exercise ventilatory and blood lactate responses. Four subjects performed a 4 min, 30 W incremental test to exhaustion at ground level (GL) and a 4 min, 20 W incremental test during three acute exposures to a simulated altitude of 4200 m; (i) normal (NAL), (ii) following 0.2 g.kg-1 ingestion of sodium bicarbonate (BAL), and (iii) following 0.5 g.day-1 ingestion of acetazolamide for 2 days prior to exposure (AAL). VE.VO2-1 increased progressively throughout the incremental tests at AL and the minimum value was not related to a change in the blood lactate response. In contrast, the VE.VCO2-1 decreased initially to reach a minimum value at the same power output for each altitude trial and was related to a lactate threshold defined by a log-log transformation (r = 0.78). This transformation of the blood lactate data was not influenced by the altered acid-base states. The relative exercise intensity corresponding to both a delta lactate of 1 mM and an absolute lactate of 4 mM was significantly increased during the AAL (79.9 +/- 12.9 and 93.9 +/- 13.7% VO2max, respectively) compared with NAL (59.1 +/- 5.5 and 78.0 +/- 5.8% VO2max, respectively). These data suggest that strong relationships exist between the ventilatory and blood lactate response during AL exposure and altered acid-base states. Further, it is concluded that, unless the acid-base status is known, the use of an absolute or delta lactate value to compare submaximal exercise should be interpreted with caution.

Arterial hypocapnia during exercise in beagle dogs.

Previous investigators have assumed that during exercise there is a tight coupling of ventilation with CO2 delivery to the lungs such that arterial blood remains isocapnic. We measured arterial blood gases in a group of 10 beagle dogs in which arterial blood sampling could be accomplished via exteriorized carotid artery loops and in six of the same dogs following chronic pulmonary denervation. Samples were taken at rest, at 15-s intervals during the first minute of unrestrained treadmill exercise at 5.0 km/h, 0% grade, and then at 2 and 3 min at the same work load. Mean resting arterial PCO2 for the control dogs was 37.1 Torr. At the onset of exercise arterial PCO2 fell progressively to a nadir of 34.6 Torr during the 30- to 45-s sampling period. Samples at 2 and 3 min remained significantly hypocapnic (PCO2 = 34.8 Torr). The arterial PCO2 and pH responses to exercise in the lung-denervated dogs were not significantly different from those of the control dogs, although arterial PO2 was lower at rest and during exercise following denervation of the lungs. The arterial hypocapnia exhibited in intact beagle dogs at the onset of exercise persists into the steady state and suggests that there is not a tight coupling of ventilation with pulmonary CO2 delivery. The similarity of the response in lung-denervated dogs suggests that intrapulmonary receptors with afferents in the vagi are not the primary mediators of the ventilatory response to exercise.

Abnormal ventilation during exercise in McArdle's syndrome: modulation by substrate availability.

We evaluated ventilation during cycle exercise in four men lacking myophosphorylase. In submaximal exercise of similar relative intensity, ventilation was higher relative to oxygen uptake in McArdle patients than in normal men. The exercise ventilatory response returned to normal after glucose infusion, by fasting to increase free fatty acid availability or by combining fasting and submaximal exercise. Excessive ventilation in exercise was potentiated by inhibiting lipolysis with nicotinic acid. The excessive ventilatory effort and resultant respiratory alkalosis may contribute to exercise intolerance.

Differences in the effect of mediastinal radiotherapy on lung function and the ventilatory response to exercise.

To examine the effect of lung inflammation on lung volumes and carbon monoxide transfer and their relationship to the ventilatory and gas exchange responses to exercise, a prospective study was performed in patients having Hodgkin's disease, with no evidence of intrathoracic involvement, who received prophylactic mantle-field radiotherapy to the chest. From 6 weeks to 6 months from the start of therapy, vital capacity (FVC) was on average 10.4% lower than during the baseline period and the total transfer of carbon monoxide (TLCO) was 10.5% lower. Minute ventilation (VE) at any given work load during an incremental exercise test was on average 10.5% higher than baseline. The stimulation of ventilation after radiotherapy was present at all work rates, but greater at high work rates. A number of other changes in the ventilatory and gas exchange responses to exercise were also seen. Most of these lay outside the range of variability observed in a group of normal subjects tested concurrently with the patients. There was a poor, but statistically significant, positive correlation between reduction in FVC and increase in VE after radiotherapy and between reduction in carbon monoxide transfer and increase in VE. A significant correlation between reduction in FVC and change in respiratory rate was also seen after radiotherapy, together with a significant inverse correlation between increase in respiratory rate and fall in tidal volume. The ratio of VE to oxygen consumption, the ventilatory equivalent for oxygen, was calculated at each work rate. There was a negative correlation between the mean increase in this parameter, averaged over all work rates, and the reduction in FVC and TLCO, i.e. the greatest stimulation of breathing relative to metabolic demand occurred in those patients with the least change in lung volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved exercise ventilatory responses after training in coronary heart disease during long-term beta-adrenergic blockade

Exercise ventilatory responses of 7 men with well-documented myocardial infarction receiving long-term beta-adrenergic blockade were studied before and after 4 months of endurance training. Observations were obtained during graded levels of upright treadmill exercise continued until 85% of the predetermined symptom-limited heart rate (working heart frequency limit). This submaximal testing procedure revealed a significant slowing of the heart rate (p less than 0.005) together with an increased oxygen pulse (p less than 0.05) after training, for what was previously a maximal work load for the working heart frequency limit. In addition, all patients achieved an increased exercise duration and work load, accompanied by significant increases in maximal oxygen uptake (p less than 0.01), oxygen pulse (p less than 0.025), and respiratory exchange ratio, for their working heart frequency limit after exercise conditioning. These results show that prolonged physical training results in physiologic adaptations to cardiac rehabilitation in the presence of long-term beta-adrenergic blockade.

Altered exercise ventilatory responses by apparent propranolol-diminished glucose metabolism: Implications concerning impaired physical training benefit in coronary patients

The effect of a single oral 40 mg dose of propranolol on ventilatory responses to symptom-limited maximal exercise were studied in 14 coronary artery disease (CAD) patients and in four normal volunteers. In both groups, there was significant reduction of carbon dioxide production, minute ventilation, and respiratory exchange ratio at matched workloads. Propranolol did not affect oxygen uptake at matched workloads. A possible explanation of these findings was that propranolol, as a result of beta blockade, inhibited stimulation of glucose metabolism during exercise. Such an effect may diminish ability of CAD patients taking propranolol to obtain beneficial results of an exercise training program.

The human ventilatory response to exercise.

The human ventilatory response to exercise.

Influence of local chemical change on ventilatory stimulus from the legs during exercise.

Experiments on normal humans are presented which were designed to study the effect of graded local chemical change in the legs on the ventilatory response to exercise. The ventilatory stimulus from proprioceptive ventilatory receptors is augmented by local chemical change which occurs in the extremities during exercise. The strength of the stimulus is proportional to the degree of physicochemical change. Submitted on May 28, 1956

Analysis of factors concerned in regulation of breathing in exercise.

ArticlesANALYSIS OF FACTORS CONCERNED IN REGULATION OF BREATHING IN EXERCISEFred S. GrodinsFred S. GrodinsPublished Online:01 Apr 1950https://doi.org/10.1152/physrev.1950.30.2.220MoreSectionsPDF (3 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Download PDF FiguresReferencesRelatedInformation Cited ByShort-term modulation of the exercise ventilatory response in young menHelen E. Wood, Gordon S. Mitchell, and Tony G. Babb1 January 2008 | Journal of Applied Physiology, Vol. 104, No. 1Point:Counterpoint: Supraspinal locomotor centers do/do not contribute significantly to the hyperpnea of dynamic exerciseTony G. Waldrop, and Gary A. Iwamoto1 March 2006 | Journal of Applied Physiology, Vol. 100, No. 3Invited Review: Neuroplasticity in respiratory motor controlGordon S. Mitchell, and Stephen M. Johnson1 January 2003 | Journal of Applied Physiology, Vol. 94, No. 1The physiological control of respirationMolecular Aspects of Medicine, Vol. 13, No. 6Allometry of respiratory and haematological parameters of arctic mammalComparative Biochemistry and Physiology Part A: Physiology, Vol. 64, No. 3Addendum1 January 1975 | Annals of the ICRP/ICRP Publication, Vol. OS_23, No. 1Human core temperature increase as a stimulus to breathing during moderate exerciseRespiration Physiology, Vol. 21, No. 2Effect of body temperature on the ventilatory response to exerciseRespiration Physiology, Vol. 8, No. 3Ventilatory responses to hind limb exercise in anesthetized cats and dogsRespiration Physiology, Vol. 6, No. 1Models of the regulation of external respiration in mammals. Problems and promisesComputers and Biomedical Research, Vol. 1, No. 1Ventilatory responses to intravenous and inspired carbon dioxide in anesthetized catsRespiration Physiology, Vol. 2, No. 1The influence of sodium amytal on the respiratory abnormalities of anxious psychiatric patientsJournal of Psychosomatic Research, Vol. 5, No. 1RESPIRATORY ADAPTATIONThe Lancet, Vol. 264, No. 6850 More from this issue > Volume 30Issue 2April 1950Pages 220-239 https://doi.org/10.1152/physrev.1950.30.2.220PubMed15424035History Published online 1 April 1950 Published in print 1 April 1950 Metrics