Modifications of blood volume alter the disposition of markers of blood volume, extracellular fluid, and total body water

Recirculatory pharmacokinetic models for indocyanine green (ICG), inulin, a nd antipyrine describe intravascular mixing and tissue distribution after i .v. administration. These models characterized physiologic marker dispositi on in four awake, splenectomized dogs while they were normovolemic, volume loaded (15% of estimated blood volume added as a starch solution), and mild ly and moderately hypovolemic (15 and 30% of estimated blood volume removed ). ICG-determined blood volumes increased 20% during volume loading and dec reased 9 and 22% during mild and moderate hypovolemia. Dye (ICG) dilution c ardiac output (CO) increased 31% during volume loading and decreased 27 and 38% during mild and moderate hypovolemia. ICG-defined central and fast per ipheral intravascular circuits accommodated blood volume alterations and th e fast peripheral circuit accommodated blood flow changes. Inulin-defined e xtracellular fluid volume contracted 14 and 21% during hypovolemia. Early i nulin disposition changes reflected those of ICG. The ICG and inulin elimin ation clearances were unaffected by altered blood volume. Neither antipyrin e-defined total body water volume nor antipyrine elimination clearance chan ged with altered blood volume. The fraction of CO not involved in drug dist ribution had a significant effect on the area under the antipyrine concentr ation-versus-time relationships (AUC) in the first minutes after drug admin istration. Hypovolemia increased the fraction of CO represented by nondistr ibutive blood flow and increased the antipyrine AUC up to 60% because nondi stributive blood flow did not change, despite decreased CO. Volume loading resulted in a smaller (less than 20%) antipyrine AUC decrease despite incre ased fast tissue distributive flow because nondistributive flow also increa sed with increased CO.