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Date of Award

1-1976

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Chemical Engineering

Supervisor

Professor I.A. Feuerstein

Abstract

This thesis contains four studies of transport phenomena and blood platelets.

The initial stage in thrombus formation is platelet adhesion to a foreign surface: platelets diffuse to the surface and then bind to it. Experiments were performed to examine the influence of haematocrit, platelet concentration, shear rate and drugs upon platelet diffusivity, the platelet wall binding rate constant and the saturation level of platelet adhesion to the surface. The level of platelet adhesion to collagen coated glass tubes were determined by measuring the axial distribution of 51Cr-γ-ray emissions from adherent 51Cr labelled platelets. The results demonstrate that the model of Grabowski et al (1972) adequately describes platelet adhesion to foreign surfaces, that platelet adhesion obeys intermediate kinetics, that the plasma skimming layer can be ignored and that platelet diffusivity is enhanced by the complex motion of red cells. An explanation for contradictions in the literature regarding the effect of drugs upon adhesion is suggested.

A design for data collection and analysis was devised for experiments in which the distribution of tracer in multicompartment systems is followed. The design requires the provision of multiple responses and analysis with a Bayesian multivariate technique. It deals with the problems of lumping and ill-conditioning inherent in descriptions of tracer distributions. The design proved successful in characterising the exchange of serotonin between the granules and cytoplasm of rabbit platelets and their surrounding medium in in vitro experiments using washed rabbit platelets.

In vitro, serotonin is freely exchangeable between platelets and their surrounding medium. To describe the potential behaviour of platelet serotonin in vivo, models were devised and fitted to the data resulting from dual label, 51Cr and 14C-serotonin, survival curves. The simplest model that adequately described the data was one in which serotonin was assumed to exchange at a finite rate between circulating platelets. The exchange rate constant from platelet to surrounding was similar to that determined in vitro.

The behaviour of adenine nucleotides in vitro and in vivo have been investigated experimentally (Reimers et al, 1975b). The in vitro exchange of adenine nucleotides between a metabolic pool and a granule pool is adequately described by first order kinetics. This information was used in a model that was fitted to data from adenine nucleotide survival and release studies. No significant metabolism or release of platelet adenine nucleotides was found in vivo.

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