Faculty Collaboration Database

The de-endothelialized rat carotid arterial graft: a versatile experimental model for the investigation of arterial thrombosis. Thromb Res 1992 Jul 01;67(1):1-14

Date

07/01/1992

Pubmed ID

1440509

DOI

10.1016/0049-3848(92)90252-6

Scopus ID

2-s2.0-0026755849 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

A novel model of arterial thrombosis was developed. A mechanical endothelium-denuding injury was created (using a scalpel blade) on harvested, freezer-stored rat carotid arteries. Vessel length of 5 mm. were grafted into the femoral arteries of recipient Sprague-Dawley rats using microvascular anastomotic technique. Patency rates in untreated animals were compared with those in animals receiving systemic aspirin or heparin. The control group patency after 2 hours of flow was 15%, while grafts in aspirin- and heparin-treated animals achieved 35% and 95% patency rates, respectively. Uninjured non-frozen carotid grafts in untreated animals yielded a 95% patency rate, while frozen grafts achieved an 80% patency. Therapeutic levels of aspirin, heparin, and urokinase were confirmed through tail bleeding and whole blood clotting tests, as well as platelet aggregation studies and scanning electron microscopy of the graft lumenal surfaces. A long-term series using syngeneic grafts placed in recipients (Lewis-to-Lewis) and employing systemic heparinization demonstrated maintenance of patency for 4 weeks. Scanning electron microscopy revealed good re-endothelialization, well advanced by one week. Histology confirmed the regrowth of endothelial cells, but showed sparse cellular repopulation of medial and adventitial layers. The mechanical injury model was compared to enzymatic de-endothelialization (using trypsin or collagenase), for which patency rates were similar (10% and 0%, respectively). Trypsin de-endothelialized vessels were tested in vitro for the amount of active trypsin remaining bound to the lumenal surface; no detectable activity was found when trypsin inhibitor was applied following trypsin treatment. The versatility of allowing both in vitro evaluation and in vivo patency assessment demonstrates the uniqueness and value of this new model, offering an avenue toward more direct investigations of surface-mediated thrombotic processes.

Author List

Cooley BC, Li X, Dzwierzynski W, Gruel SM, Hall RL, Wright RR, O'Brien EM, Fagan D, Hanel DP, Gould JS

Author

William W. Dzwierzynski MD Professor in the Plastic Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anastomosis, Surgical
Animals
Aspirin
Blood Coagulation Tests
Blood Vessel Prosthesis
Carotid Arteries
Carotid Artery Injuries
Cryopreservation
Disease Models, Animal
Endothelium, Vascular
Femoral Artery
Heparin
Male
Microscopy, Electron, Scanning
Microsurgery
Rats
Rats, Inbred Lew
Rats, Sprague-Dawley
Thrombolytic Therapy
Thrombosis
Urokinase-Type Plasminogen Activator
Vascular Patency
Wound Healing