title: The attenuation of platelet and monocyte activation in a rabbit model of extracorporeal circulation by a nitric oxide releasing polymer.
abstract: Nitric oxide (NO) has been shown to reduce thrombogenicity by decreasing platelet and monocyte activation by the surface glycoprotein, P-selectin and the integrin, CD11b, respectively. In order to prevent platelet and monocyte activation with exposure to an extracorporeal circulation (ECC), a nitric oxide releasing (NORel) polymeric coating composed of plasticized polyvinyl chloride (PVC) blended with a lipophilic N-diazeniumdiolate was evaluated in a 4 h rabbit thrombogenicity model using flow cytometry. The NORel polymer significantly reduced ECC thrombus formation compared to polymer control after 4 h blood exposure (2.8 +/- 0.7 NORel vs 6.7 +/- 0.4 pixels/cm(2) control). Platelet count (3.4 +/- 0.3 NORel vs 2.3 +/- 0.3 x 10(8)/ml control) and function as measured by aggregometry (71 +/- 3 NORel vs 17 +/- 6% control) were preserved after 4 h exposure in NORel versus control ECC. Plasma fibrinogen levels significantly decreased in both NORel and control groups. Platelet P-selectin mean fluorescence intensity (MFI) as measured by flow cytometry was attenuated after 4 h on ECC to ex vivo collagen stimulation (27 +/- 1 NORel vs 40 +/- 2 MFI control). Monocyte CD11b expression was reduced after 4 h on ECC with NORel polymer (87 +/- 14 NORel vs 162 +/- 30 MFI control). These results suggest that the NORel polymer coatings attenuate the increase in both platelet P-selectin and monocytic CD11b integrin expression in blood exposure to ECCs. These NO-mediated platelet and monocytic changes were shown to improve thromboresistance of these NORel-polymer-coated ECCs for biomedical devices.
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. tcmajor@umich.edu
authors.forename: Terry C
authors.initials: TC
authors.lastname: Major
authors.forename: David O
authors.initials: DO
authors.lastname: Brant
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Reynolds
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bartlett
authors.forename: Mark E
authors.initials: ME
authors.lastname: Meyerhoff
authors.forename: Hitesh
authors.initials: H
authors.lastname: Handa
authors.forename: Gail M
authors.initials: GM
authors.lastname: Annich
mesh_terms: D000327:Adsorption / Q000187:drug effects; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D005112:Extracorporeal Circulation; D005434:Flow Cytometry; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010976:Platelet Count; D010979:Platelet Function Tests; D011143:Polyvinyl Chloride / Q000494:pharmacology*; D011817:Rabbits; D013927:Thrombosis / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D039481:CD11b Antigen; D018950:Lipopolysaccharide Receptors; D009569:Nitric Oxide; D011143:Polyvinyl Chloride