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1. The effects of changes in ventilation and/or alveolar PCO2on the baroreflex control of heart rate have been studied in seven experiments on six young men and women who had been trained to control tidal volume and respiratory frequency at various levels independent of alveolar PCO2, during hyperoxia.

1. Three healthy young males were maintained for sessions of about 1 hr in a state of mild asphyxia (PA,O2 approximately 55, PA,CO2 approximately 45 torr), i.e. with moderately strong drives from both arterial and intracranial chemoreceptors. Tidal volume (VT), breath duration (TT) and duration of inspiration (TI) were recorded, and ventilation (VE) and duration of expiration (TE) were derived breath by breath. 2. The arterial chemoreceptor component of the drive was briefly and abruptly reduced, perhaps silenced, by three separate procedures: the inspiratory pathway was connected for two breaths to a second gas supply line containing, B, hypoxia with Pi,CO2 zero (removal of hypercapnia with maintained hypoxia); C, pure oxygen (removal of asphyxia); and D, oxygen with 40 torr added PCO2 (removal of hypoxia with maintained hypercapnia). In controls, A, the second inspiratory line contained the maintenance mixture so that the switch involved no change of inspiratory gas composition. Each type of test was repeated twenty‐four times on each subject. 3. Responses attributable to silencing of arterial chemoreceptors (i.e. with 1 1/2‐‐3 breath latencies about equal to the lung‐to‐ear circulation time) are reported elsewhere. 4. Very small responses, occurring only half a respiratory cycle after first inhalation of the test mixture, were detected by pooling all responses of each kind from all subjects. When hypoxia was withdrawn, with (C) or without (D) simultaneous withdrawal of hypercapnia, VT and VE were reduced by 3 and 2% respectively, probably because gas mixtures containing high oxygen concentrations are appreciably more viscous than hypoxic mixtures and so require more effort to breathe in and out. When hypercapnia was withdrawn with (C) or without (B) simultaneous withdrawal of hypoxia, TE was significantly lengthened (mean, + 65 +/‐ 18 msec), 5. The change of TE was discussed in relation to known effects of CO2 on airway receptors in the dog.

1. Quantitative data on the pattern of breathing in normal men and women (Gardner, 1977) have been used to derive expressions that are based on known physiological mechanisms.

Sine waves of alveolar CO2 at constant high alveolar O2, and sine waves of alveolar hypoxia (1/(PA, O2 ‐C) where C congruent to 32 torr) at constant alveolar CO2 have been administered to three subjects in each case. Six different periods of the sine waves were studied, ranging between 900 and 30 s for the CO2 sine waves and 300 and 20 s for the hypoxic sine waves. The sinusoidal variations in inspiratory and expiratory volumes (VT, I, VT, E), durations (TI, TE) and mean flows (vI, vE) produced by these manoeuvres were calculated, and the results analysed from the phase shifts of the responses. For the CO2 sine‐wave results, the peak in the TI oscillation generally appeared after the minima for VT, I and vI, but before their maxima. The peak in the TE oscillation was variable. For the hypoxic sine‐wave results, the peak in the TI oscillation showed no over‐all tendency to lead or lag the peaks of VT, I and vI. The peak in the TE oscillation generally appeared after the maxima for VT, E and vE but before their minima. For the CO2 sine‐wave results, expiratory mean flow led inspiratory mean flow, with the volumes showing no significant difference. For the hypoxic sine‐wave results expiratory volumes and mean flows led inspiratory volumes and mean flows. The results are discussed in relation to the transient responses of the components of breathing pattern obtained from other perturbations of chemical drive.

The time profile of alveolar PCO2 within the respiratory cycle has been forced to follow contrasting patterns in alternate breaths, in two different ways. Within‐breath changes (w.b.c., with a CO2‐rich inspirate supplied early or late in alternate inspirations) involved minimal alternation of end‐tidal PCO2. Between‐breath changes (b.b.c., with whole inspirates of CO2‐free or CO2‐rich gas) involved large swings of end‐tidal PCO2. As previously reported (Metias, Cunningham, Howson, Petersen & Wolff, 1981), both patterns of forcing were associated with alternation of ventilation, but only when hypoxia was present. The patterns of the alternating reflex responses in 118 runs on four human subjects in steady hypoxia are described in terms of alternation of inspiratory and expiratory tidal volume, time and mean flow. These patterns often disappeared, or changed unpredictably in mid‐run. The inspiratory pattern of reflex alternation depended in part on the type of forcing, but alternation of inspiratory tidal volume was usually observed with both types. No single pattern of expiratory alternation emerged as predominant. The pattern of reflex expiratory alternation was surprisingly independent of the pattern of inspiratory alternation: indeed, in w.b.c., but not in b.b.c., alternation of mean expiratory flow and of mean inspiratory flow were mutually exclusive. It is concluded that in man, as in cats and dogs, the arterial chemoreceptor pathway has access to various parts of the respiratory pattern generator, the exact response depending to some extent on the timing within the respiratory cycle. In particular, expiratory variables may be influenced directly through the arterial chemoreceptor pathway, i.e. without any supposedly mediating inspiratory alternation being demonstrable. The results are discussed briefly in relation to some current views on the organization of respiratory control.

1. Four human subjects exercised in hypoxia (end‐tidal partial pressure of O2 (P(ET),O2) ca 55 Torr; heart rate ca 100‐130 beats min‐1), and the contribution to the respiratory drive of the peripheral and central chemoreflex pathways have been separated on the basis of the latencies and the time courses of the responses to sudden changes of stimulus. 2. The subjects were exposed to repeated end‐tidal step changes in PCO2 of ca 3‐3.5 Torr (at nearly constant P(ET),O2) and PO2 (between ca 55 and 230 Torr) at three regions along the expiratory ventilation VE‐P(ET),CO2 response line (hypocapnia, eucapnia, hypercapnia). The dynamics of the ventilatory responses were calculated using a two‐compartment non‐linear least‐squares optimization method. 3. The component of the response attributable to the peripheral chemoreflex loop may in some subjects contribute up to 75% of the ventilatory drive during mild hypocapnic hypoxic exercise and ca 72% of the total gain following steps of P(ET),CO2 during hypoxic exercise. These data support the notion that the effectiveness of the peripheral chemoreceptor pathway is enhanced in moderate exercise. 4. During hypoxic exercise, the time delays and time constants attributed to the peripheral chemoreflex pathways (ca 3.5 and 9 s respectively) and to the central chemoreflex pathways (ca 9.5 and 47 s respectively) are some of the shortest reported. 5. The dynamics of the peripheral and central chemoreflex pathways appeared to be largely independent of each other. 6. There was a notable absence of systematic change of inspiratory and expiratory durations during the step‐induced transients.

1. We have examined the relationship between ventilation (VE), lactate (La) and arterial plasma K+ concentrations [( K+]a) during incremental exercise in six normal subjects and in four subjects with McArdle's syndrome (myophosphorylase deficiency) who do not become acidotic during exercise. 2. In normal subjects, [K+]a rose to ca 7 mM at the point of exhaustion. The time courses of the increases in VE, La and [K+]a were all similar during the exercise period. La reached its peak concentration during the recovery from exercise when both VE and [K+]a were returning to resting levels. 3. McArdle's subjects, like normal subjects, had a non‐linear ventilatory response during incremental exercise. Their [K+]a was closely related to VE throughout exercise and recovery. 4. The arterial pH of McArdle's subjects, rather than remaining constant, actually rose from the onset of exercise. 5. For a given level of exercise, the levels of VE and [K+]a were greater in the McArdle's subjects than in normal subjects. 6. These findings are consistent with the idea that hyperkalaemia may contribute significantly to the drive to breathe, especially during heavy exercise.

1. The effects of moderate degrees of hypercapnia in hypoxia and in hyperoxia on the baroreceptor‐cardiodepressor reflex have been studied in nine normal men.

1. Breathing hypoxic gas through an external dead space (ca.1200 c.c.) stimulated ventilation disproportionately. A loop (ca.250 c.c.) in the inspiratory pathway reduced the effect.