Blood analogue for thrombogenicity assessment

Abstract

The chief problem at present with artificial heart valves is their thrombogenicity, which requires the recipients to undergo dangerous anticoagulant therapy, which is not always successful. The present accepted method of testing valve thrombogenicity is implantation in experimental animals. This technique is unsatisfactory because of its high cost, the lack of control, the length of the experiments and because differences between the blood of various species render the results of dubious value. A more fundamental approach to the problem based on fluid mechanics'fails because of the complexity of the situation and because of the opposed effects of a given fluid mechanical phenomenon. The in vitro use of blood is not possible due to the need for a single pass system to avoid recirculating clots, necessitating some thirty gallons of blood for a run of only one hour. An analogue method using a fluid which does not have the disadvantages of the alternatives described above, therefore, seems worth exploring. Rennetized milk is a possible fluid for such a purpose and experiments were performed to ascertain whether it behaves in a manner analogous to blood in respect of its essential clotting properties. The first indications from the Lee-White inverted test tube test were very promising with milk behaving in a manner apparently identical to blood. Further experiments using the Stagnation Point Flow Chamber showed that there was a striking similarity in the microscopic appearance of the deposits forming at and around the stagnation point when a jet of milk/blood impinges normally onto a glass slide. A subsequent experiment, in which the fluids are pumped through a mesh, revealed that the sequence of clot growth as measured by the pressure variation upstream of the mesh is the same for both fluids. Finally, full scale tests of the clotting propensity of various heart valves were performed using an artificial heart system, which showed that the location and appearance of the clots forming on the valves with rennetized milk were similar to those found in humans and that the results were reproducible. It is, therefore, apparent that rennetized milk shows great potential as an analogue for the flow related clotting of blood and can be used for testing artificial heart valves provided care is taken in the choice of materials for construction

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