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Thromb Haemost 1990; 63(01): 044-047
DOI: 10.1055/s-0038-1645684
Original Article
Schattauer GmbH Stuttgart

Antithrombotic Effects of Recombinant Hirudin in Experimental Angioplasty and Intravascular Thrombolysis

Brigitte Kaiser
The Institute of Pharmacology and Toxicology, Medical Academy Erfurt, Erfurt, GDR
,
Antje Simon
The Institute of Pharmacology and Toxicology, Medical Academy Erfurt, Erfurt, GDR
,
Fritz Markwardt
The Institute of Pharmacology and Toxicology, Medical Academy Erfurt, Erfurt, GDR
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Publikationsverlauf

Received 03. August 1989

Accepted after revision 01. November 1989

Publikationsdatum:
02. Juli 2018 (online)

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Summary

The effect of recombinant desulphatohirudin CGP 39393 (rH) on arterial thrombus formation and especially on thrombotic reocclusion after experimental angioplasty as well as after thrombolysis was investigated in rabbits. In the femoral artery thrombi were induced after endothelial damage of the vessel wall by a balloon catheter and following stasis. After removing the thrombus by angioplasty or after lysing it by streptokinase reocclusion of the artery was observed within a relatively short period of time. Subcutaneous injection of rH reduced the incidence of both primary thrombus formation and reocclusion in dependence on the dose administered. After a dose of rH of 2 mg/kg s.c. arterial thrombus formation was completely prevented and after administering 4 mg/kg s.c. thrombotic reocclusion did also not occur. Comparative studies with heparin showed that similar antithrombotic effects were only achieved at doses of 12 mg heparin/kg s.c. The results obtained suggest a clear potential of rH for prevention of thrombotic reocclusion in clinical states.

Keywords

Recombinant hirudin - Experimental angioplasty - Thrombolysis - Reocclusion
 

  • References

  • 1 Markwardt F. Hirudin as an inhibitor of thrombin. In: Methods in Enzymology Perlman GE, Lorand L. (eds). Academic Press; New York: 1970. Vol 19 924-932
  • 2 Markwardt F. Pharmacology of hirudin: One hundred years after the first report of the anticoagulant agent in medicinal leeches. Biomed Biochim Acta 1985; 44: 1007-1013
    PubMedGoogle Scholar
  • 3 Markwardt F. The comeback of hirudin - an old-established anticoagulant agent. Folia Haematol 1988; 115: 10-23
    PubMedGoogle Scholar
  • 4 Bucha E, Nowak G, Markwardt F. Prevention of experimental coronary thrombosis by hirudin. Folia Haematol 1988; 115: 64-69
    PubMedGoogle Scholar
  • 5 Hauptmann J, Brüggener E, Markwardt F. Effect of heparin, hirudin, and a synthetic thrombin inhibitor on antithrombin III in thrombin-induced disseminated intravascular coagulation in rats. Haemostasis 1987; 17: 321-328
    PubMedGoogle Scholar
  • 6 Kaiser B, Markwardt F. Antithrombotic and haemorrhagic effects of the naturally occurring thrombin inhibitor hirudin. Folia Haematol 1988; 115: 41-46
    PubMedGoogle Scholar
  • 7 Markwardt F, Hauptmann J, Nowak G, Kleßen C, Walsmann P. Pharmacological studies on the antithrombotic action of hirudin in experimental animals. Thromb Haemostas 1982; 47: 226-229
    PubMedGoogle Scholar
  • 8 Markwardt F, Nowak G, Hoffmann J. Comparative studies on thrombin inhibitors in experimental microthrombosis. Thromb Haemostas 1983; 49: 235-237
    PubMedGoogle Scholar
  • 9 Nowak G, Markwardt F. Influence of hirudin on endotoxin-induced disseminated intravascular coagulation (DIC) in weaned pigs. Exp Pathol 1980; 18: 438-443
    PubMedGoogle Scholar
  • 10 Markwardt F, Fink E, Kaiser B, Klöcking H-P, Nowak G, Richter M, Stürzebecher J. Pharmacological survey of recombinant hirudin. Pharmazie 1988; 43: 202-207
    PubMedGoogle Scholar
  • 11 Markwardt F, Kaiser B, Nowak G. Studies on antithrombotic effects of recombinant hirudin. Thromb Res 1989; 54: 377-388
    CrossrefPubMedGoogle Scholar
  • 12 Talbot MD, Ambler J, Butler KD, Findlay VS, Mitchell KA, Peters RF, Tweed MF, Wallis RB. Recombinant desulphatohirudin (CGP 39393) anticoagulant and antithrombotic properties in vivo. Thromb Haemostas 1989; 61: 77-80
    PubMedGoogle Scholar
  • 13 Walsmann P, Kaiser B. Biochemical and pharmacological properties of recombinant hirudin. Drugs of Today 1989; 25: 473-85
    PubMedGoogle Scholar
  • 14 Grossenbacher H, Anden JA L, Bill K, Liersch M, Maerki W, Maschler R. Isolation and characterization of recombinant desul-fatohirudin from yeast, a highly selective thrombin inhibitor. Thromb Res 1987; (Suppl. 07) 34
    PubMedGoogle Scholar
  • 15 Meyhack B, Heim J, Rink H, Zimmermann W, Maerki W. Desul-fatohirudin, a specific thrombin inhibitor: expression and secretion in yeast. Thromb Res 1987; (Suppl. 07) 33
    PubMedGoogle Scholar
  • 16 Dodt J, Seemüller U, Maschler R, Fritz H. The complete covalent structure of hirudin. Localization of the disulfide bonds. Biol Chem Hoppe-Seyler 1985 366. 379-385
    PubMedGoogle Scholar
  • 17 Klöcking H-P. Zur Pharmakologie des Streptokinasepraparates Awelysin®. Folia Haematol 1976; 103: 445-455
    PubMedGoogle Scholar
  • 18 Markwardt F, Klöcking H-P, Sedlarik K, Perlewitz J, Drawert J, Hoffmann J. Tierexperimentelle Untersuchungen zur thromboly-tischen Wirkung von Streptokinase. Acta Biol Med Germ 1976; 35: 193-203
    PubMedGoogle Scholar
  • 19 Chesebro JH, Lam JY T, Badimon L, Fuster V. Restenosis after arterial angioplasty: A hemorrheologic response to injury. Am J Cardiol 1987; 60: 10B-16B
    PubMedGoogle Scholar
  • 20 Harker LA. Role of platelets and thrombosis in mechanisms of acute occlusion and restenosis after angioplasty. Am J Cardiol 1987; 60: 20B-28B
    PubMedGoogle Scholar
  • 21 Heras M, Chesebro JH, Penny WJ, Bailey KR, Lam JY T, Holmes DR, Reeder GS, Badimon L, Fuster V. Importance of adequate heparin dosage in arterial angioplasty in a porcine model. Circulation 1988; 78: 654-660
    CrossrefPubMedGoogle Scholar
  • 22 Sugrue DD, Holmes Jr DR, Smith HC, Reeder GS, Lane GE, Vlietstra RE, Bresnahan JF, Hammes LN, Piehler JM. Coronary artery thrombus as a risk factor for acute vessel occlusion during percutaneous transluminal coronary angioplasty: improving results. Br Heart J 1986; 56: 62-66
    CrossrefPubMedGoogle Scholar
  • 23 Eisenberg PR, Sherman LA, Jaffe AS. Paradoxic elevation of fibrinopeptide A after streptokinase: Evidence for continued thrombosis despite intense fibrinolysis. J Am Coll Cardiol 1987; 10: 527-530
    CrossrefPubMedGoogle Scholar
  • 24 Owen J, Friedman KD, Grossmann BA, Wilkins C, Berke AD, Powers ER. Thrombolytic therapy with tissue plasminogen activator or streptokinase induces transient thrombin activity. Blood 1988; 72: 616-620
    PubMedGoogle Scholar
  • 25 Seitz R, Blanke H, Prätorius G, Strauer BE, Egbring R. Increased thrombin activity during thrombolysis. Thromb Haemostas 1988; 59: 541-542
    PubMedGoogle Scholar
  • 26 Liu CY, Nossel HL, Kaplan KL. The binding of thrombin by fibrin. J Biol Chem 1979; 254: 10421-10425
    PubMedGoogle Scholar
  • 27 Erhardt L, Emanuelsson H, Hartford M, Johnsson H, Strandberg L-E. Coronary thrombolysis. Principles and practice. Acta Med Scand 1988 224. 413-424
    PubMedGoogle Scholar
  • 28 Gabliani G, Deligonul U, Kern MJ, Vandormael M. Acute coronary occlusion occurring after successful percutaneous transluminal coronary angioplasty: Temporal relationship to discontinuation of anticoagulation. Am Heart J 1988; 116: 696-700
    CrossrefPubMedGoogle Scholar
  • 29 Steele PM, Chesebro JH, Stanson AW, Holmes Jr DR, Dewanjee MK, Badimon L, Fuster V. Balloon angioplasty: Natural history of the pathophysiological response to injury in a pig model. Circ Res 1985; 57: 105-12
    CrossrefPubMedGoogle Scholar