This thesis, after a general introduction, is divided into two parts.
PART I STUDIES OF THE INFLUENCE OF VOLATILE ANAESTHETIC DRUGS ON
THE BLOOD FLOW AND OXYGEN UPTAKE OF THE CEREBRAL CORTEX
(1) This Part begins with a detailed account of the methodology of the
techniques used for measuring the blood flow and oxygen uptake of the
cerebral cortex in the dog including discussion of relevant anaesthetic,
anatomical and surgical details.
(2) It is demonstrated that halothane dilates the blood vessels of the
cerebral cortex, producing increases in cerebral cortical perfusion. The
intensity of cerebral vasodilatation increases with increasing concentration
of halothane so that cerebral cortical blood flow is greater with 2%
halothane than with 0.5%. Also with the higher concentration the flow
increase is maintained for at least one hour while with 0.5% halothane it
lasts only about 20 minutes. These increases in cerebral cortical blood
flow with 0.5% and 2% halothane occur despite the lowering of systemic
arterial blood pressure produced by these concentrations of halothane.
However in the case of 2% halothane, the increase in cerebral cortical blood
flow is greater when the mean arterial pressure is above 90 mm.Hg. With
the highest halothane concentration studied (4) the fall in blood pressure
is such that flow is not above control (nitrous oxide-oxygen) levels. By
administering a vasopressor drug the underlying vasodilatation produced by
4% halothane is revealed. Finally it is demonstrated that blood flow over
the cortical surface is uniform within the reproducibility of the method,
during anaesthesia with 0.5% and 2% halothane.
Halothane depresses the oxygen uptake of the cerebral cortex and the
amount of the depression is greater with 2% than with 0.5% halothane. The
E.E.G. patterns present at the times of these changes in cerebral metabolic
activity are illustrated.
As a result of the changes in the blood flow and oxygen uptake of the
cerebral cortex, the oxygen saturation of cerebral venous blood rises and
the arterio-venous differences across the cerebral cortex for oxygen, carbon
dioxide and hydrogen ion concentration are narrowed. The consequent
changes in mean tissue oxygen and carbon dioxide tensions are calculated.
(3) It is shown that trichloroethylene, in concentrations of less than l%.
increases blood flow through the cerebral cortex in the first 20 minutes of
its administration but that thereafter flow tends to return to control
values.
These concentrations of trichloroethylene reduce the oxygen uptake of
the cerebral cortex by approximately the same amount as does 0.5% halothane.
As with halothane, trichloroethylene increases venous and tissue
oxygen tensions, especially in the first 20 minutes of its administration.
(4) The findings with 1% chloroform are similar to those with halothane,
cerebral cortical blood flow increasing despite a fall in mean blood
pressure. The depression noted in oxygen uptake with this drug does not
however reach statistical significance.
(5) Finally in Part I, it is shown that cerebrovascular sensitivity to
alterations in Paco₂ is fully maintained during anaesthesia with these
drugs provided that due allowance is made for the concomitant fall in mean
blood pressure.
(6) At the conclusion of each of the above sections, the relevant
literature is fully reviewed and previous findings compared with the present
results.
(7) Part I of the thesis concludes with an extended discussion of the
possible mechanisms by which the observed changes may be produced. The
most likely explanation would appear to be that these anaesthetic drugs
relax by a "direct" action the normal tone of the cerebral arterioles and
it is postulated that they do this by inhibiting the enzymatic reaction
responsible for the generation of energy for vascular smooth muscle tone.
The interrelationships between the actions of these drugs and the
effects of alterations in blood pressure and in arterial Paco₂ are considered.
From the clinical point of view, these findings are used to describe
the sequence of changes in cerebral blood flow and metabolism which occur
with commonly employed anaesthetic techniques. The possible use of volatile
anaesthetic agents to increase the tolerance of the brain to temporary
regional or total ischaemia is then discussed in relation to the common clinical
problems of induced hypotension, cerebral arteriosclerosis and deliberate
circulatory arrest. It is concluded from this that the demonstrated
depression of cerebral oxygen requirements, especially with deep anaesthesia,
may render partial protection to the brain during ischaemia and an attempt
is made to make a quantitative prediction of the possible extension of the
period of safe circulatory arrest by this means.
PART II STUDIES OF THE INFLUENCE OF VOLATILE ANAESTHETIC DRUGS ON
CEREBROSPINAL FLUID AND CEREBRAL VENOUS PRESSURES
(1) The methodology of cerebrospinal fluid, cerebral venous and central
venous pressure measurements in dogs is first critically discussed.
Cerebral venous pressure is measured in the superior sagittal sinus and c.s.f.
pressure in the cisterna magna. Ventilation is controlled to maintain a
constant Paco₂.
(2) It is demonstrated that halothane and chloroform increase cerebrospinal
fluid pressure and that, in the case of halothane, the extent of the increase
in c.s.f. pressure is greater with 2% than with 0.5% inspired concentration.
It is also noted that the changes in c.s.f. pressure with halothane are not
maintained with time but reach a peak value in from 3-9 minutes and then
begin to fall towards the initial control value. Edith halothane
administration, c.s.f. and cerebral venous pressures both increase together
and to the same degree. Significant changes in central venous pressure do
not occur.
(3) In some of the experiments of Part I, cerebral venous pressure in the
superior sagittal sinus was measured and the results are displayed and
discussed at this point. It is observed that halothane, chloroform and
trichloroethylene in the first 20 minutes of its administration increase
cerebral venous pressure and that the changes in cerebral venous pressure
are closely correlated with increases in measured cerebral cortical blood
flow.
(4) A clinical study of lumbar c.s.f. pressure changes in patients
anaesthetised for surgical treatment of lumbar disc protrusions follows.
It is demonstrated that halothane and trichloroethylene increase c.s.f.
pressure despite careful maintenance of a constant Paco₂. The observed
changes are not the result of changes in central venous pressure. The
extent of the c.s.f. pressure rise is greater with 1% than with 0.5%
halothane but, at the same halothane concentration, the increase is smaller
in patients who are first hyperventilated. There appears to be no
important difference between the extent of the c.s.f. pressure increase with
0.9% trichloroethylene as compared with 0.5% halothane.
(5) These findings are discussed and related to the previous literature on
this subject. It is argued that the most likely explanation of the changes
observed is that the increases in cerebral blood flow seen in Part I result
in increases in the pressure within the superior sagittal sinus because
this vessel has relatively rigid walls and therefore a low compliance.
This pressure rise is transmitted back to the thin walled cerebral veins
which thereby become more distended. The blood volume on the venous side
of the cerebral circulation therefore increases and because of the low
compliance of the intracranial theca, pressure rises within the skull and
throughout the c.s.f. space. In this way the findings of the two Parts
of the thesis become mutually corroborative.
(6) Finally intraventricular c.s.f. pressure is measured in 4 patients
undergoing surgical treatment of intracranial tumours and it is shown that
considerably greater increases in cerebrospinal fluid pressure occur in
this group as compared with patients without intracranial space occupying
lesions.
(7) It is pointed out that this finding could be clinically important if
differentials of pressure are established within the central nervous
system or if the perfusion pressure of the brain (mean arterial - mean
intracranial pressure) falls below the critical level required to sustain
adequate cerebral perfusion. It is calculated that during halothane
administration in these patients with cerebral tumours, cerebral perfusion
pressure is lowered to a level at which others have demonstrated reductions
in cerebral blood flow. While not necessarily damaging in itself, this
situation is one in which the normal reserves of cerebrovascular
compensation are exhausted and cerebral ischaemia may occur at a level of
blood pressure which would not normally be considered inadequate. It is
demonstrated in one patient that prior hyperventilation avoids this
potentially hazardous position
