Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.776444
Title: Platelet adhesiveness : a possible link between the lipid and thrombogenic theories of atheroma production
Author: Fyfe, Thomas
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1970
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Abstract:
The main aim of the thesis is the investigation of the relationships between platelet adhesiveness and serum lipids in vivo. If it were possible to link these then the platelet would become a bridge between the lipid and thrombogenic theories of atheroma production. Section I includes a review of the lipid and thrombogenic theories of atheroma production together with the abundant evidence from the literature linking platelets and lipids in vitro. Evidence that platelets are involved in the formation of atheromatous plaques is also presented. The lipids measured in the experimental sections of the thesis were plasma non-esterified fatty acids(NEFA),because these are known to affect platelet function in vitro, and serum cholesterol and serum triglyceride which are known to be elevated in subjects with ischaemic heart disease. Blood sugar levels were also measured. Platelet adhesiveness was used as the measure of platelet function because it is known to be elevated in subjects with ischaemic heart disease and clearly if platelets are important in the development of atheroma, this measure is likely to be the relevant one. A further reason was that the effects of plasma NEFA on platelets in vitro appeared from the literature to be mediated by a mechanism involving adenosine diphosphate (ADP) on which platelet adhesiveness measured by the Payling Wright method also depended. The various methods of measuring platelet adhesiveness are reviewed and the chosen method, a modification of that of Payling Wright, is described in detail. The accuracy of the method was investigated and a brief study was conducted to determine the variation in platelet adhesiveness due to age, sex and the presence of ischaemic heart disease. In Section II, studies of platelet adhesiveness following stimuli causing mobilisation of body fat are described. The stimuli used were adrenocortical stimulating hormone (ACTH) in rabbits and in man, surgery, cigarette smoking, exercise, starvation, noradrenaline infusion and isoprenaline. The lipid and platelet adhesiveness changes resulting from these stimuli are detailed and compared with the findings of other workers. In Section III, the effects on platelet adhesiveness of the oral administration of substances known to affect lipid metabolism were investigated. These substances were fat, glucose, sucrose, linolenic acid, and clofibrate. The platelet adhesiveness and serum lipid changes resulting from the administration of these substances are described and the relevant literature reviewed. Section IV includes a review of the thesis along with the conclusions from the experimental work carried out. The main conclusions concerning platelet adhesiveness are:- 1) Measurement by the Payling Wright method is technically simple and is reasonably reproducible. 2) Variation in the interval between venepuncture and measurement of platelet adhesiveness affects the result. The longer this interval is, the greater the adhesiveness will be. For measurements to be comparable this interval must be kept constant. 3) Variation in platelet adhesiveness from day to day is greater than that simply due to experimental errors. 4) Platelet adhesiveness is not influenced by the age or sex of the subject. 5) It is increased significantly in subjects with ischaemic heart disease. 6) It is not increased by the acute effects of cigarette smoking. 7) It is unaffected by sucrose in the diet. 8) It is not increased in obese subjects and is not affected by weight reduction. 9) It is increased by exercise. 10) It is increased by minor stress such as the embarrassment of smoking an unlit cigarette. 11) It is increased by major, stress in the form of a surgical operation. 12) It is increased by noradrenaline and isoprenaline. 13) It is increased following the oral administration of fat. 14) It is also increased following glucose given orally. 15) It is not altered by the oral administration of linolenic acid. 16) It is not altered by clofibrate. 17) Platelet adhesiveness is not influenced directly by changes in plasma NEFA. 18) It is not affected directly by changes in serum cholesterol. 19) It is not affected directly by changes in serum triglyceride. 20) Changes in blood sugar do not directly affect platelet adhesiveness. No relationship could be demonstrated in vivo between platelet adhesiveness and serum lipids. The lipid and thrombogenic theories of atheroma production could therefore not be linked via platelet adhesiveness. The significance of the increased platelet adhesiveness found in subjects with ischaemic heart disease in relation to the development of atheroma is doubtful because of this, and because factors predisposing to ischaemic heart disease (such as cigarette smoking, obesity and possibly dietary sucrose) are not associated with Increased platelet adhesiveness while protective factors (exercise and clofibrate) are not associated with decreased adhesiveness.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.776444  DOI: Not available
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