Affiliations: [a] Department of Pediatrics, Children’s National Medical Center, Washington, DC, USA
| [b] Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA
| [c] Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS, USA
| [d] ERC–SimCenter, Mississippi State University, Starkville, MS, USA
| [e] Department of Biology, Tougaloo College, Tougaloo, MS, USA
Correspondence:
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Corresponding author: Suvankar Majumdar, MD, Division of Hematology, Center for Cancer and Blood Disorders, Children’s National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA. Tel.: +1 2024763800; Fax: +1 2024765685; E-mail: smajumdar@childrensnational.org.
Note: [1] Deceased July 31, 2013.
Abstract: BACKGROUND:Interaction of von Willebrand factor (VWF) with circulating platelets is the trigger for thrombosis in a region of arterial stenosis. These events are typically studied in vitro under conditions where platelets adhere to a VWF-coated surface. Our approach assesses platelet responses in the absence of adhesion. OBJECTIVE:To characterize extent of platelet activation and erythrocyte lysis in an artificial stenosis model. METHODS:Whole blood is perfused through a length of polyetheretherketone tubing that includes an artificial stenosis, comprising narrow-bore (89–381 μm) tubing. Secretion of [14C] serotonin and hemoglobin release was measured to evaluate platelet activation and hemolysis respectively at various perfusion rates and different stenosis dimensions. RESULTS:Platelet activation and erythrocyte lysis increased progressively with increasing perfusion rate and decreasing stenosis diameter; the length of the stenosis had negligible influence. Modest platelet activation (5–10% secretion of [14C] serotonin) occurred without significant erythrocyte lysis under a limited range of perfusion conditions (4–6 mL/min flow through a 127 μm stenosis). CONCLUSIONS:Our experimental approach mimics conditions in severe arterial stenosis or a mechanical heart valve. It could be a valuable aid in the development of novel drugs to treat arterial thrombosis and in the design of heart valves.
