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dc.contributor.authorMcDowall, David Gordonen
dc.date.accessioned2019-02-15T14:36:00Z
dc.date.available2019-02-15T14:36:00Z
dc.date.issued1967en
dc.identifier.urihttp://hdl.handle.net/1842/35227
dc.description.abstracten
dc.description.abstractThis 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.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2019 Block 22en
dc.relation.isreferencedbyen
dc.titleThe influence of volatile anaesthetic drugs on the blood flow and oxygen uptake of the cerebral cortex and on cerebrospinal fluid pressureen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnameMD Doctor of Medicineen


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