PMID- 11762330 OWN - NLM STAT- MEDLINE DCOM- 20020514 LR - 20190815 IS - 0142-9612 (Print) IS - 0142-9612 (Linking) VI - 23 IP - 2 DP - 2002 Jan TI - Blood-compatible biomaterials by surface coating with a novel antithrombin-heparin covalent complex. PG - 527-35 AB - Covalent antithrombin-heparin complex (ATH) was covalently grafted to a polycarbonate urethane (Corethane) endoluminal graft (a kind gift of Corvita Corporation) after being activated using 0.3% m/m NaOCl in 0.15 M phosphate pH 6.0. ATH graft density (1.98 x 10(-7) mol/m2) was 6 times the maximum amount of unfractionated heparin (UFH) that could be bound to polycarbonate urethane surfaces. Surface-bound ATH could be stored in sterile 0.15 M NaCl at 4 degrees C for at least 2 months with good antithrombotic activity before being implanted into rabbits. Analysis of ATH-coated tubing showed that it contained significant direct thrombin inhibitory activity. In vivo testing in a rabbit model was compared to non-activated non-coated surfaces, activated-non-coated surfaces, hirudin-coated surfaces and antithrombin (AT)-coated surfaces. The weight of the clot generated in the ATH-coated graft tubing was significantly less than the weight of the clot generated within the hirudin-coated graft (p = 0.03 with a 1-tailed Student's t test). The anticoagulant nature of ATH grafts in vivo was shown to be due to bound ATH because boththe AT-coated surfaces and non-coated but activated surfaces showed similar thromboresistant efficacy to that of untreated material (ANOVA; p < 0.05). Apart from the direct antithrombin activity that contributed to much of the prolonged patency in vivo, surface-bound ATH likely catalyzed AT inhibition of thrombin, as evidenced by a significant number of 125I-AT binding sites (> or = 1.5 x 10(-8) mol/m2). Thus, ATH appears to be a good candidate for coating cardiovascular devices, such as endoluminal grafts, with high levels of substitution and significant long-term blood-compatibility. FAU - Klement, P AU - Klement P AD - The Hamilton Clinic Hospitals Research Centre of The Hospital for Sick Children, Toronto, Ont., Canada. FAU - Du, Y J AU - Du YJ FAU - Berry, L AU - Berry L FAU - Andrew, M AU - Andrew M FAU - Chan, A K C AU - Chan AK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Antithrombins) RN - 0 (Biocompatible Materials) RN - 9005-49-6 (Heparin) SB - IM MH - Animals MH - Antithrombins/*chemistry MH - *Biocompatible Materials MH - *Blood MH - Heparin/*chemistry MH - Male MH - Rabbits MH - Surface Properties EDAT- 2002/01/05 10:00 MHDA- 2002/05/15 10:01 CRDT- 2002/01/05 10:00 PHST- 2002/01/05 10:00 [pubmed] PHST- 2002/05/15 10:01 [medline] PHST- 2002/01/05 10:00 [entrez] AID - S0142-9612(01)00135-1 [pii] AID - 10.1016/s0142-9612(01)00135-1 [doi] PST - ppublish SO - Biomaterials. 2002 Jan;23(2):527-35. doi: 10.1016/s0142-9612(01)00135-1.