The attenuation of platelet and monocyte activation in a rabbit model of extracorporeal circulation by a nitric oxide releasing polymer

• Published in: Biomaterials Vol. 31; no. 10; pp. 2736 - 2745
• Main Authors: Major, Terry C, Brant, David O, Reynolds, Melissa M, Bartlett, Robert H, Meyerhoff, Mark E, Handa, Hitesh, Annich, Gail M
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.04.2010
• Subjects: Adsorption - drug effects; Advanced Basic Science; Animals; CD11b Antigen - metabolism; Dentistry; Diazeniumdiolates; Disease Models, Animal; Extracorporeal Circulation; Flow Cytometry; Hemocompatible polymer coating; Hemodynamics - drug effects; Humans; Lipopolysaccharide Receptors - metabolism; Monocyte CD11b; Monocytes - cytology; Monocytes - drug effects; Nitric oxide; Nitric Oxide - secretion; Platelet Activation - drug effects; Platelet Adhesiveness - drug effects; Platelet Count; Platelet Function Tests; Platelet P-selectin; Polyvinyl Chloride - pharmacology; Rabbits; Thrombosis - pathology; Thrombosis - physiopathology; Time Factors; Monocyte CD11b; Platelet P-selectin; Diazeniumdiolates; Hemocompatible polymer coating; Nitric oxide; Extracorporeal circulation; Rabbit thrombogenicity model
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2009.12.028

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/cm2 control). Platelet count (3.4 ± 0.3 NORel vs 2.3 ± 0.3 × 108 /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.