title: Effect of varying nitric oxide release to prevent platelet consumption and preserve platelet function in an in vivo model of extracorporeal circulation.
abstract: The gold standard for anticoagulation during extracorporeal circulation (ECC) remains systemic heparinization and the concomitant risk of bleeding in an already critically ill patient could lead to death. Normal endothelium is a unique surface that prevents thrombosis by the release of antiplatelet and antithrombin agents. Nitric oxide (NO) is one of the most potent, reversible antiplatelet agents released from the endothelium. Nitric oxide released from within a polymer matrix has been proven effective for preventing platelet activation and adhesion onto extracorporeal circuits. However, the critical NO release (NO flux) threshold for thrombus prevention during ECC has not yet been determined. Using a 4-hour arteriovenous (AV) rabbit model of ECC, we sought to find this threshold value for ECC circuits, using an improved NO-releasing coating (Norel-b). Four groups of animals were tested at variable NO flux levels. Hourly blood samples were obtained for measurement of arterial blood gases, platelet counts, fibrinogen levels and platelet function (via aggregometry). A custom-built AV circuit was constructed with 36 cm of poly(vinyl)chloride (PVC) tubing, a 14 gauge (GA) angiocatheter for arterial access and a modified 10 French (Fr) thoracic catheter for venous access. The Norel-b coating reduced platelet activation and thrombus formation, and preserved platelet function - in all circuits that exhibited an NO flux of 13.65 x 10(10) mol x cm(-2) x min(-1). These results were significant when compared with the controls. With the Norel-b coating, the NO flux from the extracorporeal circuit surface can be precisely controlled by the composition of the polymer coating used, and such coatings are shown to prevent platelet consumption and thrombus formation while preserving platelet function in the animal.
authors.affiliation: Department of General Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109-0243, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Skrzypchak
authors.forename: Nathan G
authors.initials: NG
authors.lastname: Lafayette
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bartlett
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Zhou
authors.forename: Megan C
authors.initials: MC
authors.lastname: Frost
authors.forename: Mark E
authors.initials: ME
authors.lastname: Meyerhoff
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Reynolds
authors.forename: Gail M
authors.initials: GM
authors.lastname: Annich
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000648:ultrastructure; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D005112:Extracorporeal Circulation / Q000295:instrumentation / Q000379:methods; D006801:Humans; D008855:Microscopy, Electron, Scanning; D023421:Models, Animal; D009569:Nitric Oxide / Q000008:administration & dosage*; D020030:Nitric Oxide Donors / Q000008:administration & dosage; D015539:Platelet Activation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count; D011143:Polyvinyl Chloride / Q000737:chemistry; D011817:Rabbits
chemical_list: D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D011143:Polyvinyl Chloride