Protein adsorption on polyurethane catheters modified with a novel antithrombin-heparin covalent complex.
Highly anticoagulant covalent antithrombin-heparin complex (ATH) was covalently grafted onto polyurethane catheters to suppress adsorption/activation of procoagulant proteins and enhance adsorption/activation of anticoagulant proteins for blood compatibility. Consistency of catheter coating was demonstrated using immunohistochemical visualization of ATH. The ability of the resulting immobilized ATH heparin chains to bind antithrombin (AT) from plasma, as measured by binding of (125)I-radiolabeled AT, was greater than that for commercially-available heparin-coated catheters, and much greater than for uncoated catheters. Complementary measurements of antifactor Xa (FXa) activity and plasma protein binding were also performed. Both ATH-coated and heparin-coated catheters demonstrated functional binding of exogenous AT. However, the ATH-coated catheters gave a trend towards elevated anti- FXa activities/AT binding ratios, consistent with the higher active pentasaccharide content in starting ATH. Western blot analysis of proteins adsorbed to catheters after incubation with rabbit plasma established protein binding profiles that showed AT and albumin as major plasma proteins adsorbed to ATH-coated catheters, while AT and altered forms of fibrinogen were major plasma protein species adsorbed to heparinized catheters.
Du
Ying Jun
YJ
The Henderson Research Centre, McMaster University, 711 Concession Street, Ontario, Canada.
Brash
John L
JL
McClung
Glen
G
Berry
Leslie R
LR
Klement
Petr
P
Chan
Anthony K C
AK
D000327:Adsorption; D000818:Animals; D000991:Antithrombins; D001777:Blood Coagulation; D002404:Catheterization; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D015951:Factor Xa / Q000737:chemistry; D065427:Factor Xa Inhibitors; D005340:Fibrinogen / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry; D008422:Materials Testing; D011140:Polyurethanes / Q000737:chemistry; D011485:Protein Binding; D011817:Rabbits; D012709:Serum Albumin / Q000737:chemistry*; D013499:Surface Properties
D000991:Antithrombins; D020099:Coated Materials, Biocompatible; D065427:Factor Xa Inhibitors; D011140:Polyurethanes; D012709:Serum Albumin; D005340:Fibrinogen; D006493:Heparin; D015951:Factor Xa