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

Biomaterials. 2010 Apr;31(10):2736-45. doi: 10.1016/j.biomaterials.2009.12.028. Epub 2009 Dec 29.


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.

Keywords: Diazeniumdiolates; Extracorporeal circulation; Hemocompatible polymer coating; Monocyte CD11b; Nitric oxide; Platelet P-selectin; Rabbit thrombogenicity model.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adsorption / drug effects
  • Animals
  • CD11b Antigen / metabolism
  • Disease Models, Animal
  • Extracorporeal Circulation*
  • Flow Cytometry
  • Hemodynamics / drug effects
  • Humans
  • Lipopolysaccharide Receptors / metabolism
  • Monocytes / cytology*
  • Monocytes / drug effects*
  • Nitric Oxide / metabolism*
  • Platelet Activation / drug effects*
  • Platelet Adhesiveness / drug effects
  • Platelet Count
  • Platelet Function Tests
  • Polyvinyl Chloride / pharmacology*
  • Rabbits
  • Thrombosis / pathology
  • Thrombosis / physiopathology
  • Time Factors


  • CD11b Antigen
  • Lipopolysaccharide Receptors
  • Nitric Oxide
  • Polyvinyl Chloride