Document Detail

Modifications of blood volume alter the disposition of markers of blood volume, extracellular fluid, and total body water.
MedLine Citation:
PMID:  10565856     Owner:  NLM     Status:  MEDLINE    
Recirculatory pharmacokinetic models for indocyanine green (ICG), inulin, and antipyrine describe intravascular mixing and tissue distribution after i.v. administration. These models characterized physiologic marker disposition in four awake, splenectomized dogs while they were normovolemic, volume loaded (15% of estimated blood volume added as a starch solution), and mildly and moderately hypovolemic (15 and 30% of estimated blood volume removed). ICG-determined blood volumes increased 20% during volume loading and decreased 9 and 22% during mild and moderate hypovolemia. Dye (ICG) dilution cardiac output (CO) increased 31% during volume loading and decreased 27 and 38% during mild and moderate hypovolemia. ICG-defined central and fast peripheral intravascular circuits accommodated blood volume alterations and the fast peripheral circuit accommodated blood flow changes. Inulin-defined extracellular fluid volume contracted 14 and 21% during hypovolemia. Early inulin disposition changes reflected those of ICG. The ICG and inulin elimination clearances were unaffected by altered blood volume. Neither antipyrine-defined total body water volume nor antipyrine elimination clearance changed with altered blood volume. The fraction of CO not involved in drug distribution had a significant effect on the area under the antipyrine concentration-versus-time relationships (AUC) in the first minutes after drug administration. Hypovolemia increased the fraction of CO represented by nondistributive blood flow and increased the antipyrine AUC up to 60% because nondistributive blood flow did not change, despite decreased CO. Volume loading resulted in a smaller (less than 20%) antipyrine AUC decrease despite increased fast tissue distributive flow because nondistributive flow also increased with increased CO.
T C Krejcie; T K Henthorn; W B Gentry; C U Niemann; C Enders-Klein; C A Shanks; M J Avram
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  291     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  1999-12-20     Completed Date:  1999-12-20     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1308-16     Citation Subset:  IM    
Northwestern University Medical School, Department of Anesthesiology, Chicago, Illinois 60611-3008, USA.
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MeSH Terms
Anti-Inflammatory Agents, Non-Steroidal / diagnostic use,  pharmacokinetics
Antipyrine / diagnostic use,  pharmacokinetics
Area Under Curve
Biological Markers
Blood Volume / drug effects,  physiology*
Body Water / physiology*
Coloring Agents
Extracellular Space / physiology*
Hemodynamics / drug effects,  physiology
Hypovolemia / physiopathology
Indocyanine Green / diagnostic use,  pharmacokinetics
Inulin / diagnostic use,  pharmacokinetics
Models, Biological
Plasma Substitutes / pharmacology
Grant Support
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Biological Markers; 0/Coloring Agents; 0/Plasma Substitutes; 3599-32-4/Indocyanine Green; 60-80-0/Antipyrine; 9005-80-5/Inulin

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