Document Detail

In vivo assessment of a novel dacron surface with covalently bound recombinant hirudin.
MedLine Citation:
PMID:  10722238     Owner:  NLM     Status:  MEDLINE    
Prosthetic arterial graft surfaces are relatively thrombogenic and fail to heal with a cellular neointima. The goal of this study was to characterize the in vivo antithrombin properties of a novel Dacron surface with covalently linked recombinant hirudin (rHir) implanted in a canine thoracic aorta with high flow and shear rates. rHir was bound to a knitted Dacron patch using crosslinker-modified bovine serum albumin (BSA) as a basecoat protein. BSA was first reacted with the heterobifunctional crosslinker, sulfo-SMCC. This BSA-SMCC complex was then bound to the carboxylic acid groups of hydrolyzed Dacron patches using the carbodiimide crosslinker, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. Iodinated, Traut's-modified rHir (125I-rHir-SH) was then reacted with the Dacron-BSA-SMCC surface, thereby covalently binding 125I-rHir. Graft segments were washed and sonicated to remove any nonspecifically bound 125I-rHir. Dacron-BSA-SMCC-S-125I-rHir patches (n = 5) and control Dacron-BSA patches (n = 5) were implanted in series in the thoracic aortas of canines. These patches were exposed to nonheparinized, arterial blood flow for 2 hours. Patches were explanted and assessed for 125I-rHir loss. Antithrombin activity of explanted 1-cm2 patch segments was evaluated using a chromogenic assay with 1, 5, 10, 15 units of added thrombin. Light microscopy was performed to qualitatively examine the pseudointima. Two animals were excluded from the study owing to excessive bleeding through the knitted 125I-rHir patch. Comparison of preoperative and postoperative 125I-rHir gamma counts revealed an overall decrease of 20+/-5.4% over the period studied. Explanted 125I-rHir patch segments were able to inhibit 1, 5, and 7 NIHU of thrombin, demonstrating retained antithrombin activity. Gross and microscopic examination of the control and test Dacron surfaces showed marked differences. Dacron surfaces with covalently bound 125I-rHir had no gross thrombus and a thin pseudointima of platelets and plasma proteins. In contrast, the control patches had a thick pseudointima composed of fibrin-rich thrombus. rHir, covalently bound to Dacron patches, maintains its biologic activity as well as prevents thrombus formation on the graft surface. This novel antithrombin coating, by modifying the blood/ graft interface, may improve both short- and long-term patency in small-diameter prosthetic arterial grafts and has applications with respect to other implantable or indwelling biomaterials.
M C Wyers; M D Phaneuf; E M Rzucidlo; M A Contreras; F W LoGerfo; W C Quist
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology     Volume:  8     ISSN:  1054-8807     ISO Abbreviation:  Cardiovasc. Pathol.     Publication Date:    1999 May-Jun
Date Detail:
Created Date:  2000-03-29     Completed Date:  2000-03-29     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9212060     Medline TA:  Cardiovasc Pathol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  153-9     Citation Subset:  IM    
Division of Vascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
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MeSH Terms
Antithrombins / metabolism*
Aorta, Thoracic / pathology,  surgery
Blood Vessel Prosthesis*
Blood Vessel Prosthesis Implantation
Coated Materials, Biocompatible*
Disease Models, Animal
Evaluation Studies as Topic
Hirudins / metabolism*
Polyethylene Terephthalates / metabolism*
Recombinant Proteins / metabolism
Thrombosis / prevention & control
Grant Support
Reg. No./Substance:
0/Antithrombins; 0/Coated Materials, Biocompatible; 0/Hirudins; 0/Polyethylene Terephthalates; 0/Recombinant Proteins

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