© 1998 American Heart Association, Inc.
Original Contributions |
Pretreatment of Rabbits With Either Hirudin, Ancrod, or Warfarin Significantly Reduces the Immediate Uptake of Fibrinogen and Platelets by the Deendothelialized Aorta Wall After Balloon-Catheter Injury In Vivo
From the Department of Pathology, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
Correspondence to Dr Mark W.C. Hatton, Department of Pathology (HSC- 4N67), McMaster University Health Sciences Centre, 1200 Main St W, Hamilton, Ontario, Canada L8N 3Z5. E-mail hattonm{at}mcmaster.ca
Abstract—Fibrinogen and
platelets rapidly saturate the exposed
subendothelium of a freshly
deendothelialized aorta in vivo. As thrombin
generated within the site of injury is largely responsible for
fibrin(ogen) deposition, we questioned whether various anticoagulant
treatments would inhibit uptake of both fibrinogen and platelets in
vivo. Rabbits were anticoagulated by pretreatment with either Warfarin,
Ancrod, or recombinant hirudin. Each anesthetized,
anticoagulated (or saline-injected control) rabbit was injected IV with
rabbit 51Cr-platelets and 125I-fibrinogen
before a balloon-catheter deendothelializing (or sham)
injury of the thoracic aorta. At 10 minutes after injury, the rabbit
was exsanguinated and the aorta excised. Platelet adsorption by the
deendothelialized aorta surface was
substantially reduced in anticoagulated rabbits (controls,
2.2x105/mm2; Warfarin-treated,
1.2x105/mm2; Ancrod-treated,
5.3x104/mm2; r-hirudin–treated [5
mg/kg], 5.3x104/mm2), and a significant
reduction of fibrinogen associated with the platelet layer (from
5.3 to 1 to 2 pmol/cm2) and within the underlying
intima-media layer (from 16.9 to 5 to 6 pmol/cm2) was
observed in the r-hirudin–and Warfarin-treated rabbits. The pattern of
aorta-deposited 51Cr-platelets and
125I-fibrin in the anticoagulated rabbits corresponded well
with an assessment by transmission electron microscopy of aortic tissue
samples. We conclude that 
70% of fibrinogen uptake is thrombin
dependent and that 80% of platelet adsorption depends on
codeposited fibrin(ogen) during the 10-minute interval after balloon
injury. Pretreatment with an agent that interferes with either thrombin
or fibrin production will inhibit the immediate interaction of
fibrinogen and platelets with the freshly exposed
subendothelium.
Key Words: aorta • deendothelializing injury • platelets • fibrinogen • anticoagulants
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