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Thromb Haemost 1990; 64(04): 550-555
DOI: 10.1055/s-0038-1647356
Original Article
Schattauer GmbH Stuttgart

Properties of Thrombolytic Agents in Vitro Using a Perfusion Circuit Attaining Shear Stress at Physiological Levels

N Nishino
o   The Dept. of Physiology and BiophysicsSt. Mary’s Hospital Medical School, Paddington, London, U.K.
,
M F Scully
+   The Thrombosis Research Institute, Emmanuel Kaye Building, Chelsea, London
,
M W Rampling
o   The Dept. of Physiology and BiophysicsSt. Mary’s Hospital Medical School, Paddington, London, U.K.
,
V V Kakkar
o   The Dept. of Physiology and BiophysicsSt. Mary’s Hospital Medical School, Paddington, London, U.K.
› Author Affiliations
Further Information

Publication History

Received 03 April 1990

Accepted after revision17 July 1990

Publication Date:
25 July 2018 (online)

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Summary

A perfusion circuit was designed to investigate in vitro some of the factors which may influence the success of thrombolytic treatment in vivo. The rate of lysis of clotted plasma and different types of artificial thrombi (fibrin thrombi or whole blood thrombi) was measured in citrated plasma or whole blood under static conditions or under shear stress equivalent to the arterial or venous circulation. With both streptokinase (SK) and tissue-type plasminogen activator (t-PA) the rate of lysis of fibrin thrombi and whole blood thrombi was reduced significantly, when compared to the conventional plasma gel clot model (25-fold and 8fold, respectively). This occurred particularly with SK which showed a reduction (4-fold) in potency relative to t-PA under these conditions. Lysis of thrombi by both activators was observed to be faster in plasma than whole blood, and also faster with whole blood thrombi than fibrin thrombi. High shear stress, generally, caused a reduction in the rate of lysis of fibrin thrombi and an increase in the rate of lysis of whole blood thrombi compared to lysis rates under static conditions. Under all conditions of flow the lysis rate observed at 50 units t-PA per ml was much faster than that at 500 units per ml unlike the conventional plasma gel clot model.

 

  • References

  • 1 Collen D, de Cock F, Demarsin E, Lijnen HR, Stump DC. Absence of synergism £ between tissue-type plasminogen activator (t-PA), single-chain urokinase-type plasminogen activator (scu-PA) and urokinase on clot lysis in a plasma milieu in vitro. Thromb Haemostas 1986; 56: 35-39
    PubMedSearch in Google Scholar
  • 2 Watahiki Y, Scully MF, Ellis V, Kakkar VV. Potentation by lys-plasminogen of clot lysis by single- or two-chain urokinase-type plasminogen activator or tissue-type plasminogen activator. Thromb Haemostas 1989; 61: 502-506
    PubMedSearch in Google Scholar
  • 3 Poole JC F. A study of artificial thrombi produced by a modification of Chandler’s method. Quart J Exp Physiol 1959; 44: 377-383
    PubMedSearch in Google Scholar
  • 4 Mattesson C, Nyberg-Arrhenius V, Wallen P. Dissolution of thrombi by tissue plasminogen activator, urokinase and streptokinase in an artificial circulating system. Thromb Res 1981; 21: 535-545
    CrossrefPubMedSearch in Google Scholar
  • 5 Ljungberg J, Hedner U. Potentiated thrombolysis in a Chandler system using rt-PA and lys-plasminogen. Thromb Res 1989; 53: 569-576
    CrossrefPubMedSearch in Google Scholar
  • 6 McNicol GP, Bain WH, Walker F, Rifkind BM. Thrombolysis studied in an artificial circulation. Lancet 1965; 17: 838-842
    PubMedSearch in Google Scholar
  • 17 Kakkar VV, Scully MF. Intermittent plasminogen-streptokinase treatment of deep vein thrombosis. Haemostasis 1988; 18: 128-138
    PubMedSearch in Google Scholar
  • 8 Gottlob R, Stockinger L, Potting U, Schattenman G. Studies on thrombolysis with streptokinase. Thromb Diath Haemorrh 1971; 25: 354-378
    PubMedSearch in Google Scholar
  • 9 Schmutzler R. Klinik der thrombolytischen Behandlung. Internist 1969; 10: 21-29
    PubMedSearch in Google Scholar
  • 10 Karino T, Goldsmith HL. Rheological factors in thrombosis and haemostasis. In: Haemostasis and Thrombosis Bloom AL, Thomas DP. (eds). Churchill Livingstone; Edinburgh: 1987: 739-755
  • 11 Goldsmith HL, Karino T. Physical and mathematical models of blood flow: experimental studies. In: Erythrocyte Mechanics and Blood Flow Cokelet GR, Meiselman HJ, Brooks DE. (eds). Alan R. Liss; New York: 1980: 165-194
  • 12 Rampling MW, Challoner T. A theoretical analysis of the effects of varying fibrinogen concentration and haematocrit on the flow characteristics of blood in cylindrical tubes. Biorheology 1983; 20: 141-152
    CrossrefPubMedSearch in Google Scholar
  • 13 Rampling MW, Whittingstall P, Martin G, Bignal S, Rivers RP A, Lissauer TJ, Bailey PC. A comparison of the rheologic properties of neonatal and adult blood. Pediatr Res 1989; 25: 457-460
    CrossrefPubMedSearch in Google Scholar
  • 14 Schmid-Schoenbein H. Fluid dynamics in hemorheology in vivo. In: Clinical Blood Rheology Vol. 1 Lowe GD O. (ed). CRC Press; Boca Raton: 1988: 129-220
  • 15 Aoki N, Harpel PC. Inhibitors of the fibrinolytic system. Semin Thromb Haemostas 1984; 10: 24-41
    Thieme ConnectPubMedSearch in Google Scholar
  • 16 Sevitt S, Gallagher NG. Prevention of venous thrombosis and pulmonary embolism in injured patients. A trial of anticoagulant prophylaxis with phenindione in middle-aged and elderly patients with fractured necks of femur. Lancet 1959 2. 981-984
    PubMedSearch in Google Scholar