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.
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 i.v. 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, 2.2x10(5)/mm2; Warfarin-treated, 1.2x10(5)/mm2; Ancrod-treated, 5.3x10(4)/mm2; r-hirudin-treated [5 mg/kg], 5.3x10(4)/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 approximately 70% of fibrinogen uptake is thrombin dependent and that approximately 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.
Hatton
M W
MW
Department of Pathology, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada. hattonm@mcmaster.ca
Ross
B
B
Southward
S M
SM
DeReske
M
M
Richardson
M
M
D000721:Ancrod / Q000494:pharmacology*; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism; D002404:Catheterization / Q000379:methods*; D002860:Chromium Radioisotopes; D005340:Fibrinogen / Q000378:metabolism / Q000493:pharmacokinetics*; D006629:Hirudins / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D014859:Warfarin / Q000494:pharmacology*
D000925:Anticoagulants; D002860:Chromium Radioisotopes; D006629:Hirudins; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D014859:Warfarin; D005340:Fibrinogen; D000721:Ancrod