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Estimation of Blood Flow Heterogeneity in Human Skeletal Muscle Using Intravascular Tracer Data: Importance for Modeling Transcapillary Exchange

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Abstract

Distributed models of blood-tissue exchange are widely used to measure kinetic events of various solutes from multiple tracer dilution experiments. Their use requires, however, a careful description of blood flow heterogeneity along the capillary bed. Since they have mostly been applied in animal studies, direct measurement of the heterogeneity distribution was possible, e.g., with the invasive microsphere method. Here we apply distributed modeling to a dual tracer experiment in humans, performed using an intravascular (indocyanine green dye, subject to distribution along the vascular tree and confined to the capillary bed) and an extracellular ([3H]-D-mannitol, tracing passive transcapillary transfer across the capillary membrane in the interstitial fluid) tracer. The goal is to measure relevant parameters of transcapillary exchange in human skeletal muscle. We show that assuming an accurate description of blood flow heterogeneity is crucial for modeling, and in particular that assuming for skeletal muscle the well-studied cardiac muscle blood flow heterogeneity is inappropriate. The same reason prevents the use of the common method of estimating the input function of the distributed model via deconvolution, which assumes a known blood flow heterogeneity, either defined from literature or measured, when possible. We present a novel approach for the estimation of blood flow heterogeneity in each individual from the intravascular tracer data. When this newly estimated blood flow heterogeneity is used, a more satisfactory model fit is obtained and it is possible to reliably measure parameters of capillary membrane permeability-surface product and interstitial fluid volume describing transcapillary transfer in vivo. © 1998 Biomedical Engineering Society.

PAC98: 8745Ft, 8710+e, 8722Fy

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Authors and Affiliations

  1. Department of Electronics and Informatics, University of Padova, Italy

    Paolo Vicini & Claudio Cobelli

  2. Department of Bioengineering, University of Washington, Seattle, WA

    Paolo Vicini

  3. Division of Metabolic Diseases, City Hospital and University of Verona, Italy

    Riccardo C. Bonadonna

  4. Fourth Department of Medicine, Helsinki University Hospital, Helsinki, Finland

    Mikko Lehtovirta

  5. Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden

    Leif C. Groop

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  1. Paolo Vicini
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  2. Riccardo C. Bonadonna
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  3. Mikko Lehtovirta
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  4. Leif C. Groop
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  5. Claudio Cobelli
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Vicini, P., Bonadonna, R.C., Lehtovirta, M. et al. Estimation of Blood Flow Heterogeneity in Human Skeletal Muscle Using Intravascular Tracer Data: Importance for Modeling Transcapillary Exchange. Annals of Biomedical Engineering 26, 764–774 (1998). https://doi.org/10.1114/1.64

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