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Vena cava perfusion in situ: a tool for uptake studies
M R Nagaoka1, M Kouyoumdjian, D R Borges
1Department of Biochemistry, Universidade Federal de São Paulo, Brazil.
Journal of Pharmacological and Toxicological Methods
|February 1, 1997
Summary
Trypsin is primarily cleared by vascular endothelial cells, not liver cells, in perfusion models. Thrombin, however, is mainly cleared by liver cells, indicating distinct clearance mechanisms.
Area of Science:
- Biochemistry
- Physiology
- Vascular Biology
Background:
- Hepatocytes and Kupffer cells do not internalize trypsin or thrombin.
- Enzyme uptake may involve hepatic or vascular endothelial cells.
- Liver perfusion models may not fully represent in vivo enzyme clearance.
Purpose of the Study:
- To investigate if endothelial cell binding of enzymes is liver-specific.
- To differentiate between liver and vascular endothelial cell contribution to enzyme uptake.
- To clarify the primary sites of trypsin and thrombin clearance.
Main Methods:
- Perfused rat inferior vena cava in situ after exsanguination.
- Utilized a Krebs/BSA solution with pulsatile flow for perfusion.
- Excluded the liver from the circuit and used China ink to confirm exclusion.
Main Results:
- Trypsin was extracted by the vena cava as efficiently as by the liver.
- Thrombin uptake by the vena cava was insignificant.
- Vascular endothelial cells are the main site for trypsin removal in this model.
Conclusions:
- Trypsin clearance is largely mediated by vascular endothelial cells, not liver cells.
- Thrombin clearance is predominantly a function of liver cells.
- Enzyme uptake mechanisms differ significantly between trypsin and thrombin.