The effects of heparin and annexin V on fibrin accretion after injury in the jugular veins of rabbits.
We compared the relative abilities of unfractionated heparin and annexin V to prevent fibrin accretion onto injured jugular veins in vivo. Heparin was used to accelerate the inhibition of thrombin by antithrombin III, and annexin V was used to inhibit the assembly of the prothrombinase complex on phospholipid surfaces, thereby blocking thrombin generation. Rabbit jugular veins were isolated in situ, a 2 cm segment was injured by perfusing it with air, and then blood flow was re-established. Five minutes later, each rabbit was injected with heparin (20 U/kg) or annexin V (0.3 mg/kg) and then with 125I-fibrinogen. The amount of 125I-fibrin accumulation onto each injured vessel wall segment was measured 4 h later. Each injured vessel was completely de-endothelialized as a result of the air perfusion as demonstrated by electron microscopy. 125I-fibrin accretion onto the injured jugular veins was enhanced 2.4-fold as compared to the uninjured veins in sham-operated animals. Heparin treatment did not reduce fibrin accretion, whereas, annexin V treatment decreased fibrin accretion by 60%, p < 0.05. This latter effect was achieved without sustained circulating anticoagulation. Additional experiments confirmed that the inhibitory effect of annexin V on fibrin accretion was associated with a surface specific effect, since more annexin V bound to the injured jugular vein segments as compared to the non-injured jugular veins.(ABSTRACT TRUNCATED AT 250 WORDS)
Van Ryn-McKenna
J
J
Dept. Clinical Pharmacological Research, Dr. Karl Thomae GmbH, Biberach, Germany.
Merk
H
H
Müller
T H
TH
Buchanan
M R
MR
Eisert
W G
WG
D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology / Q000627:therapeutic use*; D001777:Blood Coagulation; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D007601:Jugular Veins / Q000293:injuries* / Q000378:metabolism; D011817:Rabbits; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000517:prevention & control
D017304:Annexin A5; D005337:Fibrin; D005340:Fibrinogen; D006493:Heparin; D013917:Thrombin