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Cardiac output and systemic transit time dispersion as determinants of circulatory mixing time: a simulation study

Department of Pharmacology, Section of Pharmacokinetics, Martin Luther University Halle-Wittenberg, Halle, Germany

Submitted 9 February 2009 ; accepted in final form 2 June 2009

A new approach to characterize the kinetics of intravascular mixing process is presented. The mixing time, defined as the time required for achieving 95% homogeneity, is calculated by numerical simulations using a circulatory model applied to the intravascular marker indocyanine green (ICG). The results suggest that the mixing time is determined by cardiac output and the relative dispersion of transit time distribution across the systemic circulation, whereby the rate of mixing increases with increasing cardiac output and decreasing transit time dispersion, and vice versa. The estimation of plasma volume from simulated ICG dilution data using the backextrapolation method shows that slow mixing is accompanied by an overestimation of blood volume. This error may be negligible for mixing times of less than 3 min but high in disease states characterized by low cardiac output and/or high transit time dispersion. In view of the role of transit time dispersion as determinant of intravascular mixing, it would be interesting to know more about the effect of disease states on systemic transit time dispersion.

plasma volume; indocyanine green; intravascular distribution; extrapolation