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Title: The influence of haematocrit and fibrinogen concentration on vascular resistance
Author: Barrie, William Wright
ISNI:       0000 0001 3448 3205
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1979
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Obstructive arterial disease is common and is a major source of morbidity. It is frequently not amenable to direct surgery, but there is no effective form of medical therapy. The use of vasodilator drugs to lower vascular resistance has been discredited. Although in theory flow should be increased by reducing blood viscosity, the flow properties of blood are complex and unpredictable in vivo. In vitro blood viscosity increases enormously at very low shear rates and a yield stress exists (that is a finite minimum force is required for flow to start). These properties are related both to haematocrit and the presence of fibrinogen, and would be of great therapeutic potential if reflected in vivo, since plasma fibrinogen concentration, and to some extent haematocrit can be safely manipulated. Initially a simple canine model was used to investigate the effect of defibrinogenation on blood flow. A critical arterial stenosis was created in one femoral artery and electromagnetic flowmeters used to measure flow through both femoral arteries and cardiac output. In both limbs of the control animals and in the non ischaemic limb of the defibrinogenated animals flow decreased as did cardiac output. However, in the ischaemic limb of the defibrinogenated animals flow relative to cardiac output increased significantly after defibrinogenation suggesting that fibrinogen might be important in low flow states. These experiments were not conclusive however as the influence of changes in vasomotor tone or coagulation could not be excluded. To try to exclude influences other than blood viscosity, an isolated canine hind limb preparation was devised in which fresh anticoagu1ated canine blood at 37°C was oxygenated and perfused in a pulsatile fashion, while accurate measurements of pressure and flow were made. Pressure/flow curves were constructed using blood haematocrit ranging from less than 20 to more than 70, at mean perfusion pressures from virtually zero to more than 150 mm Hg. The effect of fibrinogen was studied by using blood of varying natural fibrinogen concentration, defibrinogenated blood (by pre-treatment with Ancrod) and blodd whose fibrinogen concentration had been increased by the addition of purified autolgous canine fibrinogen. Protein free suspensions of red blood corpuscles/Ringer Lactate and red blood corpuscles/dextran were also studie, as was the effect of temperatures lower than 37°C. Thirty separate limb perfusion models were used to study the pressure/flow characteristics of ninety samples of blood, approximately one litre of blood being required for each perfusion experiment.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available