| Evaluation of a novel hirudin-coated polyester graft to physiologic flow conditions: hirudin bioavailability and thrombin uptake. | |
| | |
MedLine Citation:
|
PMID: 9652474 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
PURPOSE: Our laboratory has developed methods required to covalently bind recombinant hirudin (rHir) to the surface of polyester vascular grafts. Using alkaline hydrolysis of the polyester surface, carboxyl-binding sites are created on the outer periphery of each fiber. A series of static, in vitro experiments have demonstrated that surface-bound rHir rapidly removes and inhibits activated human alpha-thrombin from the reaction system; however, the performance of this modified graft material under physiologic flow conditions was undefined. METHODS: An in vitro flow loop was used to evaluate structural stability of the 125I-rHir and 131I-albumin covalently bound to the surface of 6 mm interior diameter crimped polyester grafts exposed to either constant flow (n = 4; shear rate, 300 sec(-1)) or pulsatile flow (n = 4; maximum shear rate, 780 sec(-1)) conditions for a 7-day period. In a separate series of experiments, the kinetics of thrombin-rHir interaction were evaluated through perfusion of 125I-rHir-coated grafts (n = 6) with 131I-thrombin for a 27-hour period under constant flow conditions. Identically prepared 125I-albumin-coated grafts (n = 3) were used as controls. RESULTS: Results of the stability experiments were independent of flow conditions, demonstrating moderate loss of both proteins, with rHir and albumin losses of 52.1% and 19.9% under constant flow and 49.1% and 21.6% under pulsatile flow, respectively. With results comparable with those of previous static experiments, rHir-coated grafts were significantly more effective at removing thrombin from the perfusion stream with 131I-thrombin binding densities of 3.08 +/- 0.61 and 0.64 +/- 0.04 NIHU/cm2 (p < 0.01) for rHir-coated and albumin-coated grafts, respectively. Estimates of the total amount of thrombin inactivated during the perfusion period similarly demonstrated a marked difference between the rHir-coated and control graft segments (125 +/- 8 vs. 3 +/- 14 NIHU; p < 0.005). CONCLUSIONS: These in vitro flow results illustrate that polyester grafts with covalently bound rHir can provide significant reductions in local thrombin concentration under physiologic flow conditions, and can serve as a foundation with which to understand the performance of these grafts when implanted in vivo under physiologic flow and shear rates. |
| | |
Authors:
|
S A Berceli; M D Phaneuf; F W LoGerfo |
Related Documents
:
|
2667384 - Color flow duplex screening of infrainguinal grafts combining low- and high-velocity cr... 3307654 - Blood flow in colonic anastomoses. effect of stapling and suturing. 2724454 - Effect of twist on flow and patency of vein grafts. 7356794 - Nutrient pathways in transferred patellar tendon used for anterior cruciate ligament re... 15524994 - Multistability and memory effect in a highly turbulent flow: experimental evidence for ... 17604844 - Th1/th2 balance in canine peripheral blood lymphocytes--a flow cytometric study. |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter Volume: 27 ISSN: 0741-5214 ISO Abbreviation: J. Vasc. Surg. Publication Date: 1998 Jun |
Date Detail:
|
Created Date: 1998-07-24 Completed Date: 1998-07-24 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 8407742 Medline TA: J Vasc Surg Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 1117-27 Citation Subset: IM |
Affiliation:
|
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Biocompatible Materials* Biological Availability Blood Vessel Prosthesis* Drug Interactions Drug Stability Hemodynamics Hirudins / pharmacokinetics* Humans Perfusion / instrumentation, methods Polyesters* Recombinant Proteins / pharmacokinetics Surface Properties Thrombin / pharmacokinetics* |
| Grant Support | |
ID/Acronym/Agency:
|
R01-HL21796-16/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Biocompatible Materials; 0/Hirudins; 0/Polyesters; 0/Recombinant Proteins; EC 3.4.21.5/Thrombin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Patients with venous stasis ulceration have increased monocyte-platelet aggregation.
Next Document: The differential effect of contrast agents on endothelial cell and smooth muscle cell growth in vitr...