title: Heparin-resistant thrombus formation by endovascular stents in baboons. Interruption by a synthetic antithrombin.
abstract: Intravascular mechanical support has been proposed as a solution to the frequent occurrence of vascular narrowing and occlusion after transluminal balloon angioplasty or surgical endarterectomy. Although several endovascular stents are currently in clinical use for angioplasty of larger vessels, acute thrombosis is a troublesome complication of their use with coronary angioplasty. To study thrombus formation associated with metallic mesh endoprostheses, we have evaluated stents placed inside 3-mm expanded polytetrafluoroethylene (ePTFE) grafts incorporated into chronic exteriorized arteriovenous silicone rubber shunts in baboons. We have also compared the antithrombotic capacities of heparin and the synthetic antithrombin D-phenylalanyl-L-prolyl-L-arginyl-chloromethylkene (D-FPRCH2Cl) to interrupt this platelet-dependent process for two different endovascular stents. Acute platelet deposition was continuously measured during 1 hour using gamma camera imaging of platelets labeled with indium-111 oxine. On untreated control ePTFE grafts (n = 11), 0.87 +/- 0.15 x 10(9) platelets/cm were deposited during 60 minutes. In contrast, balloon-expandable endovascular stents within ePTFE (n = 6) accumulated 4.37 +/- 0.68 x 10(9) platelets/cm (p = 0.003 compared with controls), and self-expandable stents (n = 6) accumulated 3.91 +/- 0.42 x 10(9) platelets/cm (p = 0.006 compared with controls); no difference between stents was detected in this test system (p greater than 0.5). Systemic heparin treatment did not reduce platelet deposition (4.20 +/- 0.41 x 10(9) platelets/cm at 60 minutes; p greater than 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Basic and Clinical Research, Scripps, Clinic and Research Foundation, La Jolla, California.
authors.forename: W C
authors.initials: WC
authors.lastname: Krpski
authors.forename: A
authors.initials: A
authors.lastname: Bass
authors.forename: A B
authors.initials: AB
authors.lastname: Kelly
authors.forename: U M
authors.initials: UM
authors.lastname: Marzec
authors.forename: S R
authors.initials: SR
authors.lastname: Hanson
authors.forename: L A
authors.initials: LA
authors.lastname: Harker
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000991:Antithrombins / Q000494:pharmacology*; D001792:Blood Platelets / Q000502:physiology; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D002404:Catheterization; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010215:Papio; D011138:Polytetrafluoroethylene; D012039:Regional Blood Flow; D015607:Stents / Q000009:adverse effects*; D013927:Thrombosis / Q000209:etiology* / Q000473:pathology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000991:Antithrombins; D011138:Polytetrafluoroethylene; D006493:Heparin; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone