Annals of Biomedical Engineering

, Volume 41, Issue 10, pp 2193–2205 | Cite as

Transport Limitations of Nitric Oxide Inhibition of Platelet Aggregation under Flow

  • J. L. Sylman
  • S. M. Lantvit
  • M. C. VeDepo
  • M. M. Reynolds
  • K. B. Neeves


Nitric oxide (NO) inhibits platelet aggregation at and near the site of a vascular injury by upregulation of cyclic guanosine monophosphate, which reduces the dimerization of the integrin α IIb β 3. The magnitude of NO flux from the vessel wall and the NO concentration that is necessary to inhibit platelet aggregation under physiological flow conditions is unknown. In this study, a NO releasing polymer, diazeniumdiolated dibutylhexanediamine, was integrated into a microfluidic flow assay to determine the relationship between NO wall flux and collagen mediated platelet adhesion, activation and aggregation. A NO flux equal to or greater than 2.5 × 10−10 mol cm−2 min−1 was found to abrogate aggregation, but not initial platelet adhesion, on collagen at 200 and 500 s−1 as effectively as the α IIb β 3 antagonist abciximab. The dynamic range of NO fluxes found to induce measurable inhibition of platelet aggregation spanned from 0.33 × 10−10 to 2.5 × 10−10 mol cm−2 min−1 at 200–500 s−1. These fluxes correspond to near-wall NO concentrations of 3–90 nM based on a computational model of NO transport. The model predicts that NO concentration in the platelet rich layer near the wall is kinetically limited, while NO penetration into the lumen is mass transfer limited.


Biotransport Endothelium Hemostasis Thrombosis 



This work was supported by a Scientist Development Grant (K.B.N.) from the American Heart Association, the Colorado Office of Economic Development and International Trade, and the Boettcher Foundation’s Webb-Waring Biomedical Research Award (K.B.N and M.M.R).

Supplementary material

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Supplementary material 1 (DOCX 718 kb)


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Copyright information

© Biomedical Engineering Society 2013

Authors and Affiliations

  • J. L. Sylman
    • 1
  • S. M. Lantvit
    • 2
  • M. C. VeDepo
    • 1
  • M. M. Reynolds
    • 2
    • 3
  • K. B. Neeves
    • 1
    • 4
  1. 1.Department of Chemical and Biological EngineeringColorado School of MinesGoldenUSA
  2. 2.Department of ChemistryColorado State UniversityFt. CollinsUSA
  3. 3.School of Biomedical EngineeringColorado State UniversityFt. CollinsUSA
  4. 4.Department of PediatricsUniversity of Colorado DenverAuroraUSA

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