Immunohistochemical and Histochemical Investigations on In Vivo Thrombolysis with Urokinase in Rabbits

Summary

Using human urokinase in vivo thrombolysis was studied in autologous artificial thrombi in the pulmonary circulation of rabbits by immunofluorescence and Todd’s fibrinolysis autography techniques.

As compared to the control thrombi of the untreated rabbits, a small increase of thrombolysis was found in the rabbits treated with urokinase.

Urokinase fluorescence was observed in the leukocytes, but not along the fibrin fibrils in the thrombi of the rabbits treated with urokinase. By Todd’s fibrinolysis autography, lytic areas were observed around aggregated leukocytes in the thrombi of the rabbits treated with urokinase.

The small lysis of autologous artificial thrombi of rabbits by human urokinase may be caused by (1) low affinity of human urokinase for rabbit plasminogen, (2) weak adsorption of human urokinase to rabbit fibrin, (3) phagocytosis of human urokinase by leukocytes and (4) high level of antifibrinolytic activity of rabbit plasma.

• References

• 1 Blix S. 1969; The control of plasminogen and plasmin during thrombolytic therapy. Acta Medica Scandinavica 186: 479
• 2 Chandler AB. 1958; In vitro thrombotic coagulation of the blood. Laboratory Investigation 7: 110
• 3 Fletcher AP, Alkjaersig N, Sherry S, Genton E, Hirsh J, Bachmann F. 1965; The development of urokinase as a thrombolytic agent. Maintenance of a sustained thrombolytic state in man by its intravenous infusion Journal of Laboratory and Clinical Medicine 65: 713
• 4 Genton E, Wolf PS. 1967; Experimental pulmonary embolism. Effect of urokinase therapy on organizing thrombi Journal of Laboratory and Clinical Medicine 70: 311
• 5 Gottlob R, Nashef EL, Donas P, Piza F, Kolb R. 1973; Studies on thrombolysis with streptokinase. IV. Immunofluorescent investigation on the fibrin pattern and the content of plasminogen and plasma-plasmin-inhibitors in clots and thrombi of various age Thrombosis et Diathesis Haemorrhagica 29: 393
• 6 Guest MM, Daly BM, Ware AG, Seegers WH. 1948; A study of antifibrinolysis activity in the plasmas of various animal species. Journal of Clinical Investigation 27: 785
• 7 Hamashima Y, Kyogoku M. 1968. Immunohistology. Igakushion Ltd.,; Tokyo, Japan:
• 8 Hedlin AM, Monkhouse FC, Milojevic SM. 1972; A comparative study of fibrinolytic activity in human, rat, rabbit, and dog blood. Canadian Journal of Physiology and Pharmacology 50: 11
• 9 Henry RL. 1965; Leukocytes and thrombosis. Thrombosis et Diathesis Haemorrhagica 13: 35
• 10 Hisano S. 1978; Immunofluorescent study on thrombolysis with special reference to the patterns of distribution of the contents of fibrin, plasminogen, α₂-macroglobulin and urokinase in artificial thrombi. Thrombosis and Hemostasis 39: 53
• 11 Irfan M. 1968; Fibrinolytic activity in animals of different species. Quarterly Journal of Experimental Physiology 53: 373
• 12 Koga M. 1971; Experimental study on resolution and organization of thrombi in pulmonary arteries of rabbits. Fukuoka Acta Medica 62: 525
• 13 Kopitar M, Stegnar M, Accetto B, Lebez D. 1974; Isolation and characterization of plasminogen activator from pig leucocytes. Thrombosis et Diathesis Haemorrhagica 31: 72
• 14 Maki M, Nagayama M, Endo T. 1975; Influence of urokinase on experimentally-induced DIC. Journal of Medical Enzymology 1: 496
• 15 Mohler SR, Celander DR, Guest MM. 1958; Distribution of urokinase among the common mammals. American Journal of Physiology 192: 186
• 16 Mustard JE, Kinlough-Rathbone RL, Packham MA. 1974; Recent status of research in the pathogenesis of thrombosis. Thrombosis et Diathesis Haemorrhagica Suppl 39: 157
• 17 Nowak A, Gurewich V. 1974; Thrombolysis with streptokinase in rabbits. Does response, fibrin-clot specificity and laboratory evaluation of fibrinolytic effect Thrombosis et Diathesis Haemorrhagica 31: 265
• 18 Prolopowicz J, Stormoken H. 1968; Fibrinolytic activity of leukocytes in smears of bone marrow and peripheral blood. Scandinavian Journal of Hematology 5: 129
• 19 Sakuragawa N, Takahashi K, Matsuoka M. 1975; Studies on thrombolytic therapy using urokinase. Journal of Medical Enzymology 1: 518
• 20 Sawyer WD, Alkjaersig N, Fletcher AP, Sherry S. 1961; Thrombolytic therapy. Archives of Internal Medicine 107: 21A
• 21 Tanaka K. 1968; Thrombosis. Fukuoka Acta Medica 59: 337
• 22 Todd AS, Nunn A. 1967. Fibrinolytic activity in tissue and thrombi. In Tissue Factors in the Haemostasis of the Coagulation-Fibrinolysis System, Unione Chimica Medicamenta Turin: pp 57
• 23 Ueno T, Takeuchi T, Maekawa T. 1975; Studies on in vivo metabolism of I¹²⁵-urokinase with special reference to its thrombolytic action. Journal of Medical Enzymology 1: 340