Download PDF
Thromb Haemost 1970; 24(03/04): 495-506
DOI: 10.1055/s-0038-1654259
Originalarbeiten – Original Articles – Travaux Originaux
Schattauer GmbH

Mechanism of Action of Synthetic Fibrinolytic Compounds

W Baumgarten
1   Merck Institute for Therapeutic Research West Point, Pennsylvania
,
L. I Priester
1   Merck Institute for Therapeutic Research West Point, Pennsylvania
,
D. W Stiller
1   Merck Institute for Therapeutic Research West Point, Pennsylvania
,
A. E William Duncan
1   Merck Institute for Therapeutic Research West Point, Pennsylvania
› Author Affiliations
Further Information

Publication History

Publication Date:
28 June 2018 (online)

Also available at
    Permissions and Reprints

Summary

The mechanism of dissolution of a preformed plasma clot was explored.

Our experiments showed clearly that the purified fibrin clot, made by extensive washing of a plasma clot, was resistant to lysis and that the fibrinolytic potential of the active fibrinolytic compounds was related to the presence of other plasma proteins in addition to fibrinogen.

The activation of the fibrinolytic precursors was reversible inasmuch as removal of the fibrinolytic compounds negated the fibrinolytic activity of the protein-fibrinolytic compound mixture.

Antifibrinolytic compounds which had been shown to interfer with fibrinolysis by streptokinase-activated plasminogen inhibited dissolution of the preformed plasma clot by fibrinolytically active compounds.

The fibrinolytic potential of fibrinolytic compounds was additive; however, no apparent synergism was observed.

The implication of these results to the mechanism of synthetic fibrinolysis was discussed.

 

  • References

  • 1 Aoki N, von Kaulla K. N. Inactivation of human serum plasminogen antiactivator by synthetic fibrinolysis inducers. Thrombos. Diath. haemorrh. (Stuttg) 22: 251 1969;
    PubMedSearch in Google Scholar
  • 2 Bale W. F, Helkamp R. W, Davis T. P, Izzo M. J, Goodland R. L, Contreras M. A, Spar I. L. High specific activity labelling of protein with I131 by the iodine monochloride method. Proc. Soc. exp. Biol. (N. Y.) 122: 407 1966;
    CrossrefPubMedSearch in Google Scholar
  • 3 Baumgarten W, Priester L. I, Stiller D. W, Duncan A. E. W, Giminera J. L, Loeffler L. J. 4-Aminomethylbicyclo-[2,2,2]-octane-l-carboxylic acid: A new potent antifibrinolytic agent. Thrombos. Diath. haemorrh. (Stuttg) 22: 263 1969;
    PubMedSearch in Google Scholar
  • 4 Baumgarten W, Stiller D. W. Non-enzymatic fibrinolysis. A possible explanation of the mechanism by which fibrinolysis is achieved. Abstracts, XII Congress International Society of Hematology; New York: 186UU4 Sept. 1968
    Search in Google Scholar
  • 5 Gryglewski R. The fibrinolytic activity of anti-inflammatory drugs. J. Pharm. Pharmacol 18: 474 1966;
    CrossrefPubMedSearch in Google Scholar
  • 6 Gryglewski R, Eckstein M. Fibrinolytic activity of some biacylcarboxylic acids. Nature 214: 626 1967;
    CrossrefPubMedSearch in Google Scholar
  • 7 Gryqlewski R. J, Gryqlewski T. A. The fibrinolytic activity of N-acylanthrinilates. Biochem. Pharmacol 15: 1171 1966;
    CrossrefPubMedSearch in Google Scholar
  • 8 von Kaulla K. N. Fibrinolysis induction in vitro by aromatic derivatives. Arch. Biochem 96: 4 1962;
    CrossrefPubMedSearch in Google Scholar
  • 9 von Kaulla K. N. Chemical structure and fibrinolysis induction. Thrombos. Diath. haemorrh. (Stuttg) 07: 404 1962;
    PubMedSearch in Google Scholar
  • 10 von Kaulla K. N. Inactivation of antiplasmin and complement C’ in human plasma rendered fibrinolytic by synthetic organic compounds. Thrombos. Diath. haemorrh. (Stuttg) 10: 151 1963;
    PubMedSearch in Google Scholar
  • 11 von Kaulla K. N. Chemistry of thrombolysis. Human Fibrinolytic Enzymes. Charles C. Thomas; 1963
    Search in Google Scholar
  • 12 von Kaulla K. N. A simple test tube arrangement for screening fibrinolytic activity of synthetic organic compounds. J. med. Chem 08: 164 1965;
    CrossrefPubMedSearch in Google Scholar
  • 13 von Kaulla K. N. Chemistry and pharmacology of fibrinolysis (thrombolysis). Arzneimittel - Forsch 25: 246 1965;
    PubMedSearch in Google Scholar
  • 14 von Kaulla K. N. Animal plasma as substrate for synthetic fibrinolysis inducers. Proc. Soc. exp. Biol. (N. Y.) 121: 46 1966;
    CrossrefPubMedSearch in Google Scholar
  • 15 von Kaulla K. N. Structure-dependent fibrinolytic (clot-dissolving) activity of anti-inflam - matory drugs and related compounds. Arzneimittel-Forsch 18: 407 1968; Abstr. Papers Amer. Chem. Soc. 1967 No. 153 1M.
    PubMedSearch in Google Scholar
  • 16 von Kaulla K. N. Synthetische Fibrinolytika. In: Therapeutische und experimentelle Fibrinolyse. Thrombos. Diath. haemorrh. (Stuttg.) Suppl 32: 63 1969;
    PubMedSearch in Google Scholar
  • 17 von Kaulla K. N, Ens G. On structure-related properties of synthetic organic clot-dissolving (thrombolytic) compounds. Biochem. Pharmacol 16: 1023 1967;
    CrossrefPubMedSearch in Google Scholar
  • 18 Rader R. W, Wulf R. J. Substituted salicylates and chemically-induced fibrinolysis. Fed. Proc 25: 498 1966; Abstr. 1739..
    PubMedSearch in Google Scholar
  • 19 Roubal Z, Nemecek O. Anti-inflammatory compounds exhibiting fibrinolytic activity. J. med. Chem 09: 840 1966;
    CrossrefPubMedSearch in Google Scholar
  • 20 Roubal Z, Nemecek O. Activation of fibrinolysis by derivatives of diphenyldioxopyrazoli- dine. Nature 212: 861 1966;
    PubMedSearch in Google Scholar
  • 21 Schwick H. G, Heimberger N. Biochemie der Fibrinolyse. In: Therapeutische und experimentelle Fibrinolyse. Thrombos. Diath. haemorrh. (Stuttg.) Suppl 32: 9 1969;
    PubMedSearch in Google Scholar
  • 22 Troll W, Sherry S. The activation of human plasminogen by streptokinase. J. biol. Chem 213: 881 1955;
    PubMedSearch in Google Scholar