Susan A. Ward

Effects of peripheral and central chemoreflex activation on the isopnoeic rating of breathing in exercising humans.

1. Respiratory sensation during exercise is generally considered to be related to respiratory mechanical factors which may be manifest as an abnormal relationship between the force applied to the lungs and chest wall and the resulting motion (if any); that is, a ‘length‐tension’ inappropriateness (Campbell & Howell, 1963). This suggests that there should be a direct correlation between ventilation (VE) and the associated intensity of the perceived sensation, such that the sensation associated with a particular level of VE should remain essentially constant regardless of the source of respiratory stimulation. 2. In order to establish whether certain respiratory stimuli might be ‘dyspnoeagenic’ (i.e. capable of evoking an intensity of respiratory sensation out of proportion to their influence on VE), we investigated the influence of both peripheral chemoreflex activation (induced by isocapnic hypoxia) and central chemoreflex activation (induced by hypercapnic hyperoxia) on the intensity of respiratory sensation in seven healthy adults during moderate cycle ergometer exercise (i.e. below the lactate threshold, theta 1ac). 3. In each test, an ‘isopnoea’ was established for which a particular level of VE was sustained over a prolonged period (approximately 30 min) while the proportional contributions to the ventilatory drive from either exercise and the peripheral chemoreflex or from exercise and the central chemoreflex were slowly altered to new stable levels, without the subjects knowledge, VE, tidal volume, inspiratory and expiratory durations, mean inspiratory flow, and end‐tidal PCO2 and PO2 (PET,CO2, PET,O2) were monitored breath‐by‐breath. The intensity of respiratory sensation was rated with a visual analogue scale. 4. Isopnoeic ratings of respiratory sensation were systematically greater for peripheral chemoreflex activation by isocapnic hypoxia during exercise at 50% theta 1ac (for which the degree of peripheral chemoreflex activation, estimated by hyperoxic transition or ‘Dejours’ testing, averaged approximately 23% of the total VE), compared to 90% theta 1ac during isocapnic hyperoxia. Ratings during exercise at 50% theta 1ac for central chemoreflex activation by hypercapnic hyperoxia were not systematically different from 90% theta 1ac during isocapnic hyperoxia, however. 5. As VE was stable throughout each isopnoea and the MVV (maximum voluntary ventilation) was uninfluenced by the test condition, the dyspnoea index (VE x 100/MVV) was not affected. Breathing pattern was also unaffected. 6. We conclude that in normal subjects exercising moderately, activation of the peripheral chemoreceptors by isocapnic hypoxia evokes an intensity of respiratory sensation which is out of proportion to that evoked by an isopnoeic stimulation of the central chemoreceptors with hypercapnic hyperoxia at the same level of exercise.(ABSTRACT TRUNCATED AT 400 WORDS)

Density-dependent airflow and ventilatory control during exercise

The influence of respired gas density on ventilatory control during cycle-ergometer exercise was investigated in six healthy subjects. They underwent constant-load exercise for 10 min both at 50% and 90% of the anaerobic threshold, inhaling air for the first 5 min followed abruptly by 80% helium-20% oxygen (He-O2) for the remaining 5 min (and vice versa). The He-O2 breathing elicited no discernible effect on ventilation (VI) or mean alveolar PCO2 (PACO2) at rest or at the lower work rate. However, at the higher work rate, He-O2 breathing resulted in a clear and sustained hyperventilation in all subjects. A compensatory response to the hypocapnia, consequent to the helium-induced hyperventilation, was not evident even though all subjects demonstrated a normal ventilatory responsiveness to inhaled CO2 while in this condition. These observations suggest that turbulent airflow normally imposes a constraint on the magnitude of the hyperpnea of high-intensity exercise.

Estimating Arterial PCO2 from Flow-Weighted and Time-Average Alveolar PCO2 During Exercise

The appropriateness of the ventilatory response to muscular exercise is best considered with respect to the precision of arterial PCO2 (PaCO2) regulation for moderate exercise and by the degree of the compensatory hyperventilation at work rates which engender a metabolic acidemia. But in order to avoid the necessity for intra-arterial sampling, which for sufficient data-density usually requires an indwelling catheter, several investigators have proposed non-invasive techniques for PaCO2 estimation. Techniques which are based upon assumptions of dead space volume (VD) or of a constant relationship between PaCO2 and end-tidal PCO2 (PETCO2) are not useful owing to the large inter-subject variability in the former case1 and the invalidity of the assumption in the latter.2,3 DuBois et al.4 proposed that the mean alveolar PCO2 could be derived from a “reconstruction” of the intra-breath time profile of PACO2 (i.e., time-average: PĀCO 2 T ), which in normal subjects would closely approximate PaCO2. Gumming,5 has shown that when the cumulative CO2 output (VCO2) is expressed as a function of the cumulative expired volume (V), the resulting relationship is — to a very close approximation — linear (following a small lag phase) with a slope which represents PĀCO2 (i.e., flow-weighted average: PĀCO 2 F ) and an intercept on the volume axis which is a measure of the “series” dead space (VD)). We were interested, therefore, in developing on-line, breath-by-breath techniques for determining these estimators and to define the acccuracy with which they reflect directly-measured PaCO2 during exercise.

Influence of Body CO2 Stores on Ventilatory-Metabolic Coupling During Exercise

During the steady state of moderate exercise, ventilation (VE) is closely matched to pulmonary gas exchange rates (VO2, VCO2) and, therefore, to current metabolic demands. This maintains arterial PCO2(PaCO2), pH (pHa) and PO2 at, or close to, their resting levels. For the nonsteady state, however, the presence of intervening gas stores and circulatory delays between the sites of increased metabolic rate and the lungs transiently dissociates pulmonary and tissue gas exchange. The influence of the appreciable body CO2 capacitance educes VCO2 kinetics which are substantially slower than for VO2 but similar to those of VE.1, 2, 3, 4 The close co-relation between VCO2 and VE kinetics (with little change of PaCO2) has led to the proposal of a CO2-linked control of VE during moderate exercise, although the precise mechanisms involved remain conjectural.

Dynamic Asymmetries of Ventilation and Pulmonary Gas Exchange during On- and Off-Transients of Heavy Exercise in Humans

Inferences for the physiological control mechanisms which couple: (a) tissue O2 and CO2 exchange to muscular force generation and also (b) pulmonary gas exchange to tissue gas exchange may be drawn from a precise breath-by-breath characterization of the ventilatory and pulmonary gas exchange response transients to appropriately-selected work-rate (W) forcings.1, 2, 3 As the components of these characterizations, in terms of delays (δ), time constants (τ) and gains (G), reflect the underlying physiological processes, this allows a physiological control model to be assembled. However, mathematical features of the model (i. e., the ‘what’ of parametrization) need to have as their frame of reference known, or hypothesized, physiological structures involved in the putative control scheme (i. e., the’ so what’ of model formulation).

The relation between hypoxia and CO2-induced reflex alternation of breathing in man

Four healthy young volunteers, selected for the responsiveness and steadiness of their breathing, were studied in rest and mild exercise while receiving alternate inspirates of low and high PCO2 (0 and 8.6 kPa). PACO2, oscillated between ca. 6 and 7.5 kPa (45-55 torr). PAO2 was held steady at 4-7 levels between 6 and 28 kPa (45-210 torr). Thirteen separate inspiratory and expiratory variables (volumes, times, flows) were recorded and tested for reflex alternation. Matched controls were performed. Responses were generally small in relation to the scatter. Reflex alternation of any one variable was not always evident. The incidences of the responses were, in descending order, inspiratory flows and volumes, expiratory flows and volumes, expiratory duration; inspiratory duration alternated seldom, and then with only small amplitude. Reflex alternation was more likely to be observed in hypoxia than in euoxia or hyperoxia. A tendency for the incidences to be greater in exercise than at rest was not significant, but the amplitudes of alternation showed a significant difference in favour of exercise. In a substantial minority of experiments the amplitude of reflex alternation was significantly and positively correlated with hypoxia (1/(PAO2--C)). Alternation also occurred frequently in another substantial minority of experiments in which, however, there was no significant amplitude-hypoxia correlation. It was concluded that these two groups probably differed not so much in the form of the amplitude-hypoxia relation as in respect of the extent of the scatter in the observations. The results are consistent with interaction of non-steady-state with steady-state signals at the arterial chemoreceptors.

Naloxone and the ventilatory response to exercise in mana

SummaryEndogenous opiate peptides are known to exert a depressant action on ventilation (

Gas-Exchange Inferences for the Proportionality of the Cardiopulmonary Responses During Phase 1 of Exercise

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