Professor Y. Ikeda gave a final report on methods and main conclusions on the effects of flow on endothelial cell function. Methods that were studied were (i) morphology, (ii) immunoassay of platelet and EC released products and (iii) immunoassay of EC-platelet reaction products, such as thrombin: ATIII:heparin, and this is done with and without presentation by immunoregulatory molecules such as cytokines. Of specific interest was the expression of tissue factor, and the combined influence of TNF-a and shear on this process. Both cone-and-plate and parallel-plate devices were useful.
Prof. J. Hubbell gave an intermediate report on the transport and biorheological issues related to the delivery of drugs to the artery wall and to thrombus adherent to the arterial wall. These methods included (i) various catheter designs with or without an imposed pressure gradient or electrical field, (ii) with permanent implants, such as graft sleeves, and (iii) with polymer depots, either within the artery lumen, within the media, or surrounding the adventitia.
Prof. M. Frojmovic presented a report on various issues in the study of platelet-platelet and platelet-leucocyte interactions under flow. There are biological issues, including presentation of new receptors (e.g., P-selectins), exposure to new agonists, and activation of intracellular signal transduction. There are biophysical issues, including flow-dependent collision, adhesion, and de-adhesion. These both relate to device issues, e.g., platelet-platelet collision in a Couette flow vs. platelet-thrombus collision in a parallel-platelet flow.
Prof. M. Frojmovic presented a brief overview of biorheological issues in the design of flow devices for clinical monitoring of thrombosis and coagulation. This served as an introduction for discussion of clinical devices.
Prof. D. Gabriel presented a brief overview of the clinical issues in monitoring of the thrombotic state, also as an introduction for discussion of clinical devices.
Prof. Marc Hoylaerts presented experience in the use of rectangular capillaries for the study of platelet deposition. Protein is deposited, the free surface is blocked, platelets are perfused, fixative is perfused, and then staining is performed. Quantification is performed by microscopy.
Prof. Y. Ikeda presented experience in the use of the quartz crystal microbalance in the study of platelet deposition on protein-coated surfaces. It was observed that the standard calibration equations that are employed for molecular overlayers are not appropriate for cellular overlayers, due to the viscoelasticity of the cellular overlayer. Nevertheless, the results could be quantitatively analyzed to provide real-time measurements of platelet deposition under various pathological conditions.
Dr. E. Heilman, from Dade-Behring, gave an overview on the PFA 100 instrument, which is based on the closure of a capillary with a collagen coating. The instrument is now used clinically to diagnose Glanzmann's thrombosthemia, von Willebrand's disease, and aspirin-induced bleeding.
Dr. C. Li, from Xylum, presented results with the Clot Signature Analyser. This orifice instrument has a flow through an orifice and a flow through a channel with a collagen fiber within. The instrument operates with native whole blood.
Dr. D. Varon, from the University of Tel Aviv, presented results on the use of cone-and-plate methodology for assay of platelet function. Both adhesion and aggregation are measured. Platelet deposition is examined both on extracellular matrix (produced by cell culture) and on polystyrene.
Dr. R. Hillman, from Accumetrics, was scheduled but was unable to attend.
Dr. J. Mitchell, from Hemodyne, presented methods for study of the forms involved in clot retraction. Over time after introduction of thrombin, the mechanical properties of the fibrin network and of the contractile form generated by the platelet are measured. The method has also been used to monitor fibrinolysis.
Each of the methods developed and described above has been used clinically and has been calibrated in standard coagulopathies.
Extensive discussion followed, with general agreement to hold a major symposium on the above topic of "Rheological Bedside Devices for Monitoring and Managing Vascular Diseases: Current Status and Future Needs" at the Washington meeting in 1999.
New topics were suggested, including "Rheological Models for Bleeding/Thrombotic Disorders", and (2) "Flow Effects on Blood Cell Function".
Attendance was excellent with 45 participants