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An Integrated Computational and Experimental Model of Nitric Oxide–Red Blood Cell Interactions

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Abstract

In blood vessels, nitric oxide homeostasis is maintained by its formation by endothelial nitric oxide synthase and its consumption in smooth muscle cells and in vascular lumen by red blood cell (RBC) encapsulated hemoglobin (Hb). Free hemoglobin has a very high reaction rate (k Hb–NO ~ 107 M−1 s−1) with NO as compared to RBC–Hb. Mechanisms of reduced NO uptake by RBC–Hb has been extensively studied in recent years. A critical factor in the investigation of NO–RBC interactions is delivery of NO. Common NO delivery methods include use of NO donors and bolus saturated NO solutions, which delivers NO homogenously and only in the vicinity of bolus, respectively. In this study, we developed a flow system that uses gaseous delivery of NO through a polymeric semi-permeable membrane to obtain precise and uniform NO concentrations for NO–RBC interactions. We conducted experiments using the flow system to study the effect of NO concentrations, hematocrit and RBC suspension flow rates on NO–RBC interactions. We developed a computational model to simulate NO transport and to estimate the reaction rate constant for NO–RBC interaction in the flow system. Our results showed that NO consumption of RBCs (i) increased linearly with an increase in available NO, and (ii) decreased with increase in RBCs suspension flow rate. We estimated the reaction rate constant for NO–RBC interactions to be 0.2 × 105 M−1 s−1 which is ~1250-fold lower than NO consumption by free hemoglobin and ~2.5–20 fold slower than reported NO–RBC reaction rate.

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Acknowledgments

We thank Dr. Charles Maxwell for fresh pig blood. This study is supported by Arkansas Biosciences Institute, AHA grant 0530050N and NIH grants R01 HL084337 and R15 HL087287.

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  1. Biomedical Engineering Program, College of Engineering, University of Arkansas, 223 Engineering Hall, Fayetteville, AR, 72701, USA

    Prabhakar Deonikar & Mahendra Kavdia

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Deonikar, P., Kavdia, M. An Integrated Computational and Experimental Model of Nitric Oxide–Red Blood Cell Interactions. Ann Biomed Eng 38, 357–370 (2010). https://doi.org/10.1007/s10439-009-9823-x

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