| Engineering analyses were carried out for two new modes of therapy. First, rheological changes in red cells upon interaction with some perflurochemicals were studied. Perfluorochemicals (PFCs) are being developed for use as erythrocyte substitutes to carry oxygen to tissue in acute crises. Oxypherol, a commercially available PFC preparation used in animal tests, reduces erythrocyte deformability in the presence of plasma. This undesirable effect further complicates oxygen delivery by erythrocytes. Experiments indicate that one or more plasma proteins must be present to observe Oxypherol-induced reduction in erythrocyte deformability, but the rheological effect on the red cells is not protein-specific. Neither platelet activation nor enhanced protein adsorption could account for the mechanism of altered erythrocyte flexibility. Using F-19 NMR, it was found that a small amount of Oxypherol droplets adsorbed on the erythrocyte surface. The amount of adsorbed droplets increases when Oxypherol was incubated with erythrocytes in the presence of plasma, in parallel with a decrease in erythrocyte deformability. Therefore, it seems likely that the loss of deformability of the erythrocytes is caused by the adsorption of small droplets of Oxypherol on the red cells. For the second analysis, a mathematical model was developed for reaction and transport aspects of thrombolytic therapy. This therapy is used to treat conditions arising from thrombus-induced obstruction of arteries which supply nourishment in the human body. Thrombolytic therapy activates the fibrinolytic system present in the bloodstream to produce the enzyme plasmin, which lyses the clot and thereby removes the cause of the occlusion. Streptokinase is a widely used thrombolytic agent. A kinetic model predicted that new regimes of administration of streptokinase would produce higher circulating levels of plasmin; this is potentially a more effective therapy. The fluid mechanics of flow in the local region containing the thrombus showed complex flow patterns; simple calculations indicated that both convective and diffusive mass transport were important, but that the former were more so. Thrombolytic therapy could therefore be optimized by study of reaction dynamics and fluid and mass transport. |
