K.B. Saunders

Transient, steady-state and rebreathing responses to carbon dioxide in man, at rest and during light exercise.

1. The transient ventilatory response to CO2, measured using short pulses at constant inflow, was compared with the steady‐state response at rest and during exercise at 50 W, and with the rebreathing response at rest, in nine healthy subjects. At rest CO2 was given at flow rates of 0.2 and 0.4 l min‐1 and during exercise, to compensate for the smaller inhaled CO2 fraction as ventilation increased, at flow rates of 0.4 and 0.8 l min‐1. 2. We calculated two indexes of gain for the transient response: the ratio of the peaks of the ventilation and PCO2 pulses, and the ratio of their integrals. 3. The steady‐state response was greater than the transient response at rest and during exercise, but there was no correlation between the two. The rebreathing response was greater than both. Both the transient and the steady‐state responses were greater during exercise than at rest. 4. To assess alinearity, the steady‐state responses to the two CO2 flow rates were compared. At rest, there was no significant difference. During exercise, the response was greater to 0.4 than 0.8 l min‐1, indicating alinearity concave downwards. 5. We conclude that the transient response as we calculate it is not representative of steady‐state gain, and that the CO2 response in light exercise is steeper, and concave downwards in shape. The rebreathing technique overestimates CO2 sensitivity near the control point.

Hypoxia following voluntary hyperventilation during exercise in man

The importance of carbon dioxide in the control of ventilation during exercise was tested by emptying CO2 stores by voluntary hyperventilation. Healthy subjects were studied after 3 min hyperventilation down to an end-tidal PCO2 of about 20 mmHg on a background of steady exercise at 75 W. Control runs were performed when the hyperventilation was made isocapnic by the addition of CO2. Following hypocapnic hyperventilation, there was a period when ventilation fell below control and this was accompanied by a fall in end-tidal PO2 (minimum 48 mmHg) and oximeter reading (minimum 73%). Ventilation rapidly returned to baseline following isocapnic hyperventilation and hypoxia was not seen. A mathematical simulation suggested that brain PCO2 recovered more slowly than arterial PCO2 and that at the times that ventilation was depressed central chemoreceptor PCO2 would have been low. We conclude that CO2 provides a crucial drive for maintaining adequate ventilation during steady exercise and that the central chemoreceptor may be involved.

Ventilatory sensitivity to single breaths of CO2 around the control point in man

We used single inspiratory capacity breaths of 5, 6 or 8% CO2 in air to obtain ventilatory responses in normal subjects, with ensemble averaging of repeated runs to define stimulus and response (Protocol 1). We also compared the effect of an inspiratory capacity (IC) breath of 8% CO2 with that of two tidal volumes (TV) at the same concentration (Protocol 2). The ventilatory response was defined first as the ratio of peak changes in ventilation and end-tidal PCO2, and secondly by the ratio of their integrals. We obtained group mean values of 0.21 L min-1 mmHg-1 for the peak method and 0.80 L min-1 mmHg-1 for integrals (Protocol 1). There was no significant difference between IC and TV response values (Protocol 2) either by the peak method (0.17 vs 0.19 L min-1 mmHg-1) or by integrals (0.47 vs 0.53 L min-1 mmHg-1). A significant decrease in ventilation was seen in the second tidal volume 8% CO2 breath, even though the stimulus was unperceived by four out of five subjects. CO2 responses can be obtained from these techniques, but the necessary analysis is too cumbersome for general use. Taking a deep breath had no detectable separate effect, but CO2 in the airway may depress ventilation even at concentrations which the subject cannot detect.

Effects of deep breaths on subsequent ventilation in man during rest and exercise.

1. We examined the effects of twenty‐four to thirty inspiratory capacity (IC), expiratory capacity (EC) and vital capacity (VC) breaths on subsequent breathing pattern in five normal subjects at rest. 2. During IC breaths and following EC and VC breaths at rest, end‐tidal CO2 pressure (PET,CO2) fell by 7.5, 8.5 and 9.5 mmHg, respectively. In the group analysis significant inhibition of ventilation of 1.5 l min‐1 was seen after the IC breath but not after EC or VC breaths. 3. We repeated the study with five normal subjects under conditions of higher ventilatory drive, namely 50 W exercise (one subject was common to both groups). 4. During exercise, the drop in PET,CO2 was smaller (4.0, 3.5 and 4.0 mmHg, respectively, with IC, EC and VC breaths) but ventilation was inhibited to a greater extent. Ventilatory undershoot was seen after all three types of deep breaths. 5. We propose that the expiration to residual volume in EC and VC breaths abolished the hypocapnic inhibition of ventilation at rest, possibly by a deflation reflex which was not sufficiently powerful to overcome the ventilatory undershoot during exercise. Our results also support the view that the slope of the CO2 response curve is steeper near the control point during exercise.

Immediate ventilatory response to sudden changes in venous return in humans.

We changed venous return transiently by postural manoeuvres, and by lower body positive pressure, to see what happened simultaneously to ventilation. Cardiac output was measured by a Doppler technique. In seven subjects, after inflation of a pressure suit to 80 and 40 mmHg at 30 deg head‐up tilt, both cardiac output and ventilation increased. Ventilation increased rapidly to a peak in the first 5 s, cardiac output more slowly to a steady state in about 20 s, at 80 mmHg inflation. After inflation to 80 mmHg in six subjects at 12.5 deg head‐up and 30 deg head‐down tilt, cardiac output did not change in the first, and fell in the second case. There were no significant changes in ventilation. On release of pressure there were transient increases in both cardiac output and ventilation, with ventilation lagging behind cardiac output, in contrast to (2) above. In five subjects, elevation of the legs at 30 deg head‐up tilt caused a rise in both cardiac output and ventilation, but in two subjects neither occurred. In all seven subjects there was a transient increase in cardiac output and ventilation when the legs were lowered. Ventilation and cardiac output changes were approximately in phase. We were therefore unable to dissociate entirely increasing cardiac output from increasing ventilation. The relation between them was certainly not a simple proportional one.

Decreasing the particle size of aerosols of local anaesthetic by heating

We used a cascade impactor and radioactive labelling to determine the distribution of particle size in aerosols from several commercially available nebulizers, and the effect of heating on the size distribution. Mass median diameter (MMD) of the unheated aerosols ranged from 1.4 to 4.8 μm and this was reduced by heating to a range of 06 to 1.9 μm. Bupivacaine (0.5%) can be given as an aerosol after heating with minimal side-effects from anaesthesia of the upper respiratory tract, since the smaller, concentrated, particles are deposited deeper in the lung. This may have clinical applications.

Modelling the Ventilatory Response to Pulses of Inhaled Carbon Dioxide in Exercise

Recent computer-assisted techniques permit experimental inhaled CO2 stimuli to be precisely shaped, for example to a square wave, while alveolar PO2 (PAO2) is held constant. The respiratory control mechanisms sensitive to CO2 have then been modelled as a two-compartmental first order system, with central and peripheral components, each with a defined time delay (mainly circulatory), time constant and gain1.