chemoreceptive areas which are sensitive to pH in their
environment. They mapped out these areas on the medulla
surface as being chemosensitive by applying local
anaesthesia which induced apnea in anaesthesised cats.
However, these chemoreceptive areas do not morphologically
show any receptor cells, thus suggesting that these pH sensitive respiratory centre neurons are located super ficially in these areas in the brain stem.
It has not been resolved whether the pH effect is due only to changes in extracellular pH or whether it is due to changes in intracellular pH.
The sensitivity of the central chemoreceptive areas
can be expressed as ventilation response to pH changes
in the brain extracellular fluid. Since the ventilatory
responses are different when stimulated by pH changes induced
by changing HCO%" and by inspired PGOp, it is difficult
to put absolute values on the sensitivity. However,
maximum and minimum values were computed from data in
goats by Pappenheimer et al 1965 (by Sorensen 19?1).
Minimum values were found by pH changes due to changing
HCO^~ and maximum values by inspired PGOp.
In man Severinghaus et al 1965 calculated the
ventilatory response to CSF pH changes during COp breathing in man, assuming minimal contribution from the peripheral receptors and found that the change in ventilation per change in CSF pH was larger than that found in goats.
46 ;
Different techniques for measuring COg response in diseases. From the time Scott 1920 observed that there was a
reduced ventilatory response to COg in patients with
airways obstruction, workers have developed several methods to measure accurately this response in disease.
Gherniack and Snidal 1956 observed reduced ventilatory
response to GOg when they introduced viscous resistance
at the mouth of subjects, suggesting that this reduced response is solely due to the airways obstruction limiting
the normal ventilatory flow. Similarly, Eldridge and
Davis 1959 suggested that the increased resistance was responsible for the diminished ventilatory response.
Since this v/as so, workers tried to measure a response
other than that of ventilation to assess this GOg drive
in patients. Mechanical work of breathing as the
measured response was used by Eldridge and Davis 1959 and o
BrodVsky et al I960. They found that this mechanical
work in normals, in normals with added external resistance, and in patients with airways obstruction all show similar
slopes when plotted against arterial PGOp. This
suggested that this measurement of response would measure accurately GOp drive without being affected by resistance, even though the PCOg intercept for patients with
obstruction were higher than that for normal.:subjects. Similarly Milic Emili and Tyler 1963 found that added viscous resistance reduced ventilatory response to COp
by 50%, without affecting the inspiratory work rate response. However, when obstructive airways patients are separated into the hypercapnie and normocapnie subjects the response of ventilation to GOp expressed as work rate is lower in
1
4-7 I
:|
the hypercapnies and in patients with elevated
bicarbonate levels (Alexander et al 1955, Cherniack
and Snidal 1956 and Park 1965).
Lane and Howell 1970 also used inspiratory work load performed during COp rebreathing to assess their
subjects' COp drive. A significant positive correlation
was found between work rate response and dyspnoes; patients with reduced response also experienced little
dyspnoea despite severe airways obstruction. There was
also a significant negative correlation between work rate
and high resting PaCOp, suggesting that a diminished work
rate response would mean reduced central COp sensitivity.
Similarly Pritts et al 1959 measured mechanical
work as the measured response to COp and found the response
in 4 emphysematous patients to be normal.
O'Donnell and Hood 1971, in their study of 15
patients with obstructive lung disease and hypercapnia,
used changes in intrathoracic pressure as the COp drive
index. This is done by measuring the end-inspiratory and
end-expiratory intrathoracic pressures using an intra-
oesophageal baTbon during COp rebreathing. They showed
that with increase in P .COp, the intrathoracic pressure
difference increases. Patients showed a decreased COp
ventilatory response when compared to normals but the
"pressure drive" response was the same suggesting that
this "pressure drive" index'is independent of airways
resistance.
48
as the oxygen cost of breathing during increased breathing. Richards et al 1958, in nine emphysematous subjects with elevated PaCOp, measured the oxygen consumption for the increased ventilation and found that the response measured
was similar to that of the normals. However, the
ventilation attained at a given increase in oxygen consumptio was much less in the patients than in the normals, suggest ing that the reduced ventilatory response v/as due to
mechanical factors.
Brodovsky et al I960, measured oxygen consumption (as well as the mechanical efficiency^of the respiratory muscles^ and likewise found no difference in COp response
in their patients and normal subjects. When measuring
oxygen consumption as the measured response an assumption
has to be made. This is the efficiency of the oxygen
cost in terms of the development of mechanical work is similar during COp breathing and room air in the same
individual as well as when comparing different individuals. The measurement of the integrated EMG of the diaphragm as the output from the respiratory centre was also employed to separate reduced central sensitivity from increased
mechanical obstruction. Lourenco and Miranda 1968, found
that the EMG activity is decreased in patients with elevated resting PaCOp when compared to that of normals and normocapnie airway obstruction patients.
Repeatability of slopes of COg response using rebreathinp method.
49
ments were quite-repeatable. Workers have noted the
variability of "normal" COp response from subject to subject, without being able to identify the cause of
variation. Schaefer 1958, suggested that differences
in adrenal and sympathetic responses to hypercapnia might be responsible.
Jennett 1968, observed a large variability in individuals on repeated testings (in 9 subjects in 59 trials, with a mean coefficient of variation of 57% in
individual subjects). However, Jennett and Short 1975,
found that when 25 subjects were studied twice in an interval of 15 minutes, the average difference in slopes is of plus or minus 28%, but there is not a significant difference between the first and second tests.
Using a slight modification of Read's method,
Strachova and Plum 1975, in a study of 45 subjects (normal subjects, hospitalised normals, and patients with acid-base and neurologic disorders), found more repeatable results, with an average coefficient of variation of 5.6% for each subject (for repeated tests in single day it was 5.8% and
for long term repeats of a month it was 5.6%). Differences
in values found in an individual subject, rarely exceeded 2 standard deviations of the mean, and they suggested that the method is reliable for assessing effect of disease on the response to COp.
Clark 1968, found in his study of 56 patients with chronic airways obstruction, repeatability is good with a
coefficient of variation of about 10%. Within subject