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WH Dascombe, C Hong, KO Garrett, JG White, VA Lyle, JL Miller and PC Johnson
Department of Surgery, University of Pittsburgh, PA.
Early thrombosis of artificial microvascular grafts (AMG, grafts < or =
2 mm internal diameter) prevents their reliable clinical use. The present
studies were undertaken to examine the effect of hirudin, a
thrombin-specific inhibitor, and of the F(ab')2 fragment of PG-1, a
monoclonal antibody (MoAb) directed against guinea pig platelet membrane
glycoprotein Ib (GPIb), on AMG patency in an animal model. One- centimeter
long segments of expanded polytetrafluoroethylene (ePTFE), 0.88 mm internal
diameter, were serially implanted as interposition grafts in the guinea pig
femoral arterial systems bilaterally. A control group was treated with 0.5
mL saline intravenously (IV) 30 minutes before limb 1 and limb 2 graft
implantation. Three experimental groups were treated with 0.5 mL saline IV
before limb 1 graft implantation as an animal control and with either 0.5
mL saline containing 1.25 mg/kg IV PG-1 F(ab')2, (which inhibits
ristocetin- induced platelet agglutination and von Willebrand factor
binding), hirudin 1 mg/kg IV, or a combination of both agents before limb 2
graft implantation. GPIb inhibition, thrombin inhibition, and the
combination resulted in a significant prolongation of AMG patency (P <
.005). Whereas thrombin inhibition with hirudin prolonged AMG patency
similar to that observed with GPIb inhibition, the combination of GPIb and
thrombin inhibition provided the overall longest prolongation of AMG
patency. These results indicate that both platelet membrane GPIb and
thrombin play a role in AMG thrombosis.
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| Copyright © 1993 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||