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M A Contreras

Publications and source records attributed to M A Contreras.

42 records · Page 3Linked to original sources
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In vivo assessment of a novel dacron surface with covalently bound recombinant hirudin.

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.

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PubMedDate not supplied

Monitoring platelet interactions with prosthetic graft implants in a canine model.

This study shows that prosthetic arterial grafts stimulate platelets for as long as 1 year after implantation in a canine model. Carotid-to-distal aorta Dacron (DuPont, Wilmington, DE) grafts (0.8 x 50.0 cm) were tunneled subcutaneously over the right dorsal side, allowing for percutaneous arterial sampling. Thromboxane B2 (TxB2) levels were evaluated at the proximal anastomosis (w), 5.0 (x), 25.0 (y), and 50.0 (z) cm distal from w, and platelet counts and mean platelet volumes were monitored at sites w and z. TxB2 levels increased after blood entered the graft and progressively increased until the blood exited at the distal anastomosis. Platelet counts did not significantly change across the graft. Over time, systemic platelet counts decreased to approximately 50% of each dog's pregraft baseline levels and remained depressed over a 1 year period. Mean platelet volumes peaked 1-3 weeks after implant and remained greater than pregraft levels. Examination of the graft luminal surface showed a developed pseudointima characteristically similar to that which develops in mature human vascular grafts. These results suggest that healed vascular grafts in canines continue to stimulate platelet release of TxB2, reduce systemic platelet counts, and increase mean platelet volumes over 1 year. These data further suggest that platelets are stimulated by the graft and consumed.

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