The Effects of Diabetes Mellitus, Coronary Artery Disease, Exercise and Stanozolol on the Fibrinolytic Enzyme System in Man

Small, Michael (1986) The Effects of Diabetes Mellitus, Coronary Artery Disease, Exercise and Stanozolol on the Fibrinolytic Enzyme System in Man. MD thesis, University of Glasgow.

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Abstract

This thesis reviews the literature relating vascular disease to fibrinolysis and describes a number of clinical studies which have attempted to evaluate the components of the fibrinolytic enzyme system in a variety of different medical disorders and in healthy subjects. In these clinical settings a comparison has been made between the plasma fibrinolytic activity (fibrin plate: ex vivo fibrinolysis) and BBeta 15-42. fragment (in vivo plasmin-mediated fibrinolysis) as indicators of fibrinolysis, and the relative importance of fibrinolysis and coagulation has been estimated by measuring both plasmin (BBeta 15-42) and thrombin generation (fibrinopeptide A). The effect on fibrinolysis of a number of clinical and laboratory measures have been made with fibrinolysis studied in the basal state and following pharmacological intervention and exercise. In a double-blind, placebo-controlled study, exercise in young healthy male subjects was shown to be associated with enhanced plasma fibrinolytic activity without a concomitant activation of coagulation. The rise in plasma fibrinolytic activity was not influenced by prior administration of beta-blocker drugs and therefore adrenergic mechanisms made no contribution to the exercise enhanced plasma fibrinolytic activity. Exercise in middle-aged men was related, in part, to the workload and was associated with both thrombin and plasmin generation suggesting that the enhanced fibrinolysis may have been secondary to activation of coagulation. In men of the same age group with coronary artery disease no alterations of haemostasis were detected. Whether such defective in vivo fibrinolysis was related to coronary artery disease per se, to the lack of changes in coagulation or to the workload intensity requires further study. Defective fibrinolysis has been noted in coronary artery disease and in 100 men with angiographically defined coronary artery disease we have examined the inter-relationships between fibrinolysis, lipids and hormones and the relationships between these 3 factors and the severity of coronary artery disease. We found that patients with a previous myocardial infarction had raised oestradiol levels but that these were not related to the tests of fibrinolysis. While higher alpha2-antiplasmin levels were found in hypertriglyceridaemia,. lipid levels were not associated with altered fibrinolysis. We have provided evidence that BBeta 15-42 is a reliable indicator of in vivo fibrinolysis by showing significant correlations with plasminogen (negative) and FDP's (positive). This is consistent with activation of fibrinolysis (increased BBeta levels) being associated with decreased plasminogen and raised FDP's. Apart from fibrinogen levels, none of the laboratory measures were related to the severity of coronary artery disease which fails to provide support for defective basal fibrinolysis being associated with coronary artery disease. The anabolic steroid, stanozolol is felt to be the most promising oral agent to induce long-term enhancement of fibrinolysis. We have performed a number of studies with this drug and have found that, given via the intramuscular route, stanozolol did not decrease fibrinogen and alpha2-macroglobulin levels (unlike the orally administered drug ) and while it led to rapid and sustained changes in plasma fibrinolytic activity and plasminogen in young healthy males, it failed to effect such changes on fibrinolysis in elderly patients with medical illness. In studies using oral stanozolol we have shown that it caused plasmin-mediated fibrinolysis in normal subjects but not in type II (non-insulin dependent) diabetic patients. We have also noted favourable effects on carbohydrate metabolism in diabetics given stanozolol, but adverse hormonal and lipid effects in other studies. The weight of evidence suggests that stanozolol is not a useful anti-thrombotic agent. (Abstract shortened by ProQuest.).

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Medicine, Physiology, Kinesiology, Pharmacology
Date of Award: 1986
Depositing User: Enlighten Team
Unique ID: glathesis:1986-77354
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 11:53
Last Modified: 14 Jan 2020 11:53
URI: http://theses.gla.ac.uk/id/eprint/77354

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