11 micromanometer which in turn gave a deflection on the

pen-recorder. Thus different heights on the recorder

chart correspond to known pressure.

°) Rebreathing techniques (similar to Read's 1967) The initial hag CO. concentration was 7# GOg in 0^ for normal subjects. In patients, different initial concentrations were put into the bag, depending on the patients resting PaCOg. Thus the normocapnie patients had an initial bag PGOg similar to that for normal

subjects, whilst in the hypercapnie patients, the initial bag POOg was slightly higher. This ensured rapid

equilibrium on rebreathing, between PGOg in bag, lungs

and pulmonary capillary blood. ( Campbell and Howell 1962 ) All the subjects underwent the same rebreathing

procedure. The subjects were seated comfortably and breathed room air for 1 minute to get used to the ex­ perimental equipment. Rebreathing lasted for 4 to 5 minutes or loss if they could not carry on.

The GOg ventilatory response curve can be expressed

—1 ... ]

in terms of its slope or "8" (litres min~ mm.Hg"") and the intercept of the x axis us B (in mm.Hg.) as shown by Lloyd et al., 1958.

The slopes in normal subjects were mainly obtained for data between about 43 and 70 mm.Hg PGOg.

Blood gas determinations

The resting arterial hCOg in patients was determined by direct measurements from blood samples. PaCOg was also checked by using an Indirect method. The subjects re­ breathed from a small bag (2 litre) of 100^ oxygen for

12

1.5 mlns., rested for two minutes, then rebreathed again for 20 seconds. The concentration of GOp in the bag was determined by a COg analyser and after corrections made for arterial-venous difference, the

PaCOg was determined. In all cases where these checks

were carried out, there was no significant difference in the resting PaCOg measured by direct blood deter­ mination or by the indirect method.

Calibration of COg analyser.

For the normal subjects and normocapnie patients, the COg analyser was calibrated for 1# to 10# COg. For the hypercapnie patients the gain on the COg analyser was reduced so that a maximum reading of 12# COg can be obtained by extrapolation on the COg calibration curve. Method used in Isocapnic Hynoxia Test, (progressive)

The method used in this experiment is similar to the one used by Rebuck et al., 197$.

In this experiment a rebreathing circuit was used (Fig. iA-a )A six-litre rebreathing bag in a sealed box

(iii)

was filled with 7# COg, 20 to 22# Og, and the rest nitrogen. End-tidal measurements of Og and COg were continuously made from samples taken near the mouth and after passing through the CO^ and Og meters were returned to the bag. The gas analysers used were an infra-red COp analyser accuraUe to - 0.1# over range 0 - 10#, and a paramagnetic Og analyser (Servomex} with a 90# response time of 0.15 sec, and - 0.1# accuracy.

Ventilation was measured using a pneumatograph attached to the outlet in the box and connected to a electro-spirometer. A two-way low-resistance Douglas

13

valve was attached to the niouth-piece (as used in the -j_•1 ’'l GOg rebreathing experiment). The opening pressure of -d

the valve 5 at 1 cnuHgO, provided an imperceptible transient t

occlusion of inspiration. An outlet from the mouth­

piece connected to the manometer measured the pressure i

between the mouth and the valve and this was recorded in

a fast-responding 2-channel recorder. The pressure change : was recorded in one channel and in the other channel, the 1

pressure wave signal was electronically differentiated and

recorded as spikes. /

The resistance of the circuit was 0.6 cm.HgO/litre 6 per sec.

Before starting the experiment, the subject was made

to sit comfortably for 10 minutes after which he breathed v

room air through the mouth piece for a further 5 minutes. After this neriod, at the end of a normal expiration, .

the tap was turned to connect the subject to the rebreath- 1 ing bag. The subject was asked to take 2 to 3 deep - breaths to facilitate mixing between lung and bag. When ^ the end-tidal PGOg plateau is reached, usually between 15

to 20 seconds a pump connecting the bag to a soda lime #

cannister by-pass was switched on. A variable flowmeter

was used to control the flow through the COg scrubber so 1

that the end-tidal PCOp was kept constant to within 1

+ 1 mm.Hg. of the initial mixed-venous level throughout

the experiment. The initial POg ranged from 140 to 160 mm.Hg. and was allowed to decrease to a minimum of 50 to

4-0 mm.Hg.

PCOp, ]^0g and ventilation were continuously recorded

14

Repeat testing

Repeat tests were made for the both types of

hypercapnie response tests (also with added resistance) and the hypoxic response test. To prevent bias in the

treatment of results, the results from the first test

only were used for statistical analysis.

Treatment of data from hypoxia test. (Fig,1A~1b)

The ventilatory and (dp/dt) responses to hypoxia and the corresponding bag POg was calculated for every 50 seconds throughout rebreathing, until the last 50

seconds where it was calculated for 15 seconds. The mean,

ventilation (from individual tidal volumes) and the mean (dp/dt)^_^ (from individual spikes) was calculated._{liicl A. «} The resulting relationship obtained, when ventilation

was plotted against hyperbolic. This hyperbolic relationship was converted to a linear function as

suggested by Weil et al., 1970,by an equation similar to one originally suggested by Lloyd et al., 1958. This equation relates ventilation and alveolar POp as follows, Vp = V^0+A/(PA0g-52), _{-1—i C,^} where _I..J is minute ventilation in litres per minute; PAOp is the alveolar Og tension in mm.Hg and V^O (or VO) is the asymptote for ventilation obtained by extrapolation. Parameter A describes the shape of the curve in that the bigger the value of A, the greater is the hypoxic ventilatory drive. The constant 52 represents the PAOg at which the ventilation - PAOg

curve approaches infinity. Byrne-Quinn et al., 1971, Weil et al., 1972, Rebuck et al., 197$ &ud Kelsen et al.,

15