title: Relationship between release rate and surface concentration for heparinized materials.
abstract: Mathematical models are used to predict surface concentrations that result from the release of heparin into flowing blood and stagnant or well-mixed plasma. Two release rates--4 X 10(-2) and 3 X 10(-5) micrograms/cm2 min--are considered, which describe elution from an ionically heparinized material and from an immobilized heparin-PVA hydrogel, respectively. When heparin is released at the higher rate into blood flowing in cylindrical tubes with dimensions characteristic of the vasculature, or annular tubes representative of catheter experiments, a minimum surface concentration of 0.5 micrograms/mL is attained virtually at the tube inlet. Release at the lower rate requires tube lengths of several thousand meters to attain the same critical value. Similarly, heparin released from a suspension of beads at the higher rate leads to critical surface concentrations of 0.2 micrograms/mL within a fraction of a second in stagnant plasma, or ca. 5 s in a well-mixed environment. At the lower release rate, 45 or 100 min must elapse before the same level is achieved. These results support the validity of 4 X 10(-2) micrograms/cm2 min as a reasonable minimum release rate to produce a heparin microenvironment sufficient to prevent thrombosis. The lower rate is shown to be insufficient to generate a critical concentration, thus supporting the argument that heparin-PVA does not owe its biological activity to a heparin microenvironment. The model equations can be applied to the release of any material to determine surface concentrations.
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects; D002404:Catheterization; D006493:Heparin / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D013927:Thrombosis / Q000517:prevention & control
chemical_list: D006493:Heparin