Biochemistry, Pharmacokinetics, and Dynamics of Single- and Two- Chain Urokinase

  • Kurt Huber
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 193)


Enzymes in urine capable of digesting fibrin were described as early as 1885 [1], but the name urokinase was first used by Sobel et al. about 45 years ago [2].


Acute Myocardial Infarction Thrombolytic Agent Plasminogen Activation Clot Lysis Recombinant Tissue Plasminogen Activator 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sahli W. Ueber das Vorkommen von Pepsin und Trypsin im normalen menschlichen Harn. Pflügers Arch Physiol 36:209, 1885.CrossRefGoogle Scholar
  2. 2.
    Sobel GW, Mohler SR, Jones NW, Dowdy ABC, Guest MM. Urokinase: An activator of plasma profibrinolysin extracted from human urine. Am J Physiol 171:768, 1952.Google Scholar
  3. 3.
    Astedt B. No crossreaction between circulating plasminogen activator and urokinase. Thromb Res 14:535, 1979.PubMedCrossRefGoogle Scholar
  4. 4.
    Kok P. Separation of plasminogen activators from human plasma and a comparison with activators from human uterine tissue and urine. Thromb Haemost 41:734, 1979.PubMedGoogle Scholar
  5. 5.
    De Bruin PAF, Crama-Bohbouth G, Verspatet HW, Verheijen JH, Dooijewaard G, Weterman IT, Lamers CBHW. Plasminogen activators in the intestine of patients with inflammatory bowel disease. Thromb Haemost 60:262, 1988.PubMedGoogle Scholar
  6. 6.
    Grondahl-Hansen J, Kirkeby L, Ralfkiaer E, Kristensen P, Lund LR, Dano K. Urokinase-type plasminogen activator in endothelial cells during acute inflammation of the pancreas. Am J Pathol 135:631, 1989.PubMedGoogle Scholar
  7. 7.
    Kirchheimer JC, Koller A, Binder BR. Isolation and characterization of plasminogen activators from hyperplastic and malignant prostate tissue. Biochim Biophys Acta 797:256, 1984.PubMedGoogle Scholar
  8. 8.
    Layer GT, Cederholm-Williams SA, Gaffney PJ. Houlbrook S, Mahmoud M, Pattison M, Burnand KG. Urokinase — the enzyme responsible for invasion and metastasis in human breast carcinoma? Fibrinolysis 1:237, 1987.CrossRefGoogle Scholar
  9. 9.
    Markus G. The relevance of plasminogen activators to neoplastic growth: A review of recent licerature. Fnzyme (Basel) 40:158, 1988.Google Scholar
  10. 10.
    Huber K, Kirchheimer JC, Ermler D, Bell C, Binder BR. Determination of plasma urokinase-type plasminogen activator antigen in patients with primary liver cancer — characterization as tumor-associated antigen and comparison with alpha-fetoprotein. Cancer Res 52:1717, 1992.PubMedGoogle Scholar
  11. 11.
    Huber K, Kirchheimer JC, Sedlmayr A, Bell C, Ermler D, Binder BR. Clinical value of determination of urokinase-type plasminogen activator antigen in plasma for detection of colorectal cancer: Comparison with circulating tumor-associated antigens CA 19-9 and carcinoembryonic antigen. Cancer Res 53:1788, 1993.PubMedGoogle Scholar
  12. 12.
    Saskela O, Montesano F. Cell-associated plasminogen activation: Regulation and physiological functions. Ann Rev Cell Biol 4:93, 1988.Google Scholar
  13. 13.
    Pepper MS, Montesano F. Proteolytic balance and capillary morphogenesis. Cell Differ Dev 32:319, 1991.CrossRefGoogle Scholar
  14. 14.
    Lupu F, Heim DA, Bachmann F, Hurni M, Kakkar VV, Kruithof EKO. Plasminogen activator expression in human advanced atherosclerotic lesions. Arterioscler Tbromb Vasc Biol 15:1444, 1995.Google Scholar
  15. 15.
    Van Hinsberg VWM, Regulation ot the synthesis and secretion of plasminogen activators by endothelial cells. Haemostasis 18:307, 1988.Google Scholar
  16. 16.
    Vasalli JD, Dayer JM, Wohlwend A, Belin D. Concomitant secretion of prourokinase and of plasminogen activator-specinc inhibitor by cultured human monocytes-macrophages. Exp Med 159:1653, 1984.CrossRefGoogle Scholar
  17. 17.
    Hart PH, Burgess DR, Vitti GF, Hamilton JA. Interleukin-4 stimulates human monocytes to produce tissue-type plasminogen activator. Blood 74:1222, 1989.PubMedGoogle Scholar
  18. 18.
    Park S, Karker LA, Marzec UM, Levin EG. Demonstration of single chain urokinase-type plasminogen activator on human platelet membrane. Blood 73.1121, 1989.Google Scholar
  19. 19.
    Bachmann F. Fibrinolysis. In Verstraete M, Vermylen J, Lijnen R, Arnout J (eds). Thrombosis and Haemostasis 1987. Leuven University Press 1987:227.Google Scholar
  20. 20.
    Kirchheimer JC, Binder BR. Urokinase antigen in plasma: Age and sex dependent variations. Thromb Res 36:643, 1984.PubMedCrossRefGoogle Scholar
  21. 21.
    Ichinose A, Fujikawa K, Suyama T. The activation of pro-urokinase by plasma kalhkrein and its inactivation by thrombin. J Biol Chem 261:3484, 1984.Google Scholar
  22. 22.
    Hauert J, Nicoloso G, Schleunig WD, Bachmann F, Schapira M. Plasminogen activators in dextran sulfate-activated euglobulin fractions: A molecular analysis for factor XII-and prekallikrein-dependent fibrinolysis. Blood 73:994, 1989.PubMedGoogle Scholar
  23. 23.
    Kobayashi H, Schmitt M, Goretzki L, Chucholowski N, Calvete J, Kramer M, Gunzler WA, Janicke F, Graeff H. Cathepsin B efficiently activates the soluble and the tumor-cell receptor-bound form of the proenzyme urokinase-type plasminogen activator (Pro-uPA). J Biol Chem 266:5147, 1991.PubMedGoogle Scholar
  24. 24.
    Goretzki L, Schmitt M, Mann K, Calvete J, Chucholowski N, Kramer M, Gunzler WA, Janicke F, Graeff H. Effective activation of the proenzyme form of the urokinase-type plasminogen activator (pro-uPA) by the cysteine protease cathepsin L. FEBS Lett 297:112, 1992.PubMedCrossRefGoogle Scholar
  25. 25.
    Günzler WA, Steffens GJ, otting F, Buse G, Flohe L. Structural relationship between human high and low molecular mass urokinase. Hoppe-Seyler’s Z Physiol Chem 363:133, 1982.PubMedGoogle Scholar
  26. 26.
    Stump DC, Lijnen HR, Collen D. Purification and characterization of a novel low molecular weight form of single-chain urokinase-type plasminogen activator. J Biol Chem 261:17120, 1986.PubMedGoogle Scholar
  27. 27.
    Marcotte PA, Dudlak D, Leski ML, Ryan J, Henkin J. Characterization of a metalloproteinase which cleaves with high site-specificity the glu(143)-leu(l44) bond of urokinase. Fibrinolysis 6:57, 1992.CrossRefGoogle Scholar
  28. 28.
    Collen D, Zamarron C, Lijnen HR, Hoylaerts M. Activation of plasminogen by pro-urokinase. II. Kinetics. J Biol Chem 261:1259, 1986.PubMedGoogle Scholar
  29. 29.
    Gurewich V, Pannel R. Inactivation of single-chain urokinase (pro-urokinase) by thrombin and thrombin-like enzymes: Relevance of the findings to the interpretation of fibrin-binding experiments. Blood 69:769, 1987.PubMedGoogle Scholar
  30. 30.
    Holmes WE, Pennica D, Blaber M, Rey MW. Guenzler WA, Steffens GJ, Heyneker HL. Cloning and expression of the gene for pro-urokinase in Escherichia coll. Biotechnology 3:923, 1985.CrossRefGoogle Scholar
  31. 31.
    Blasi F. Surface receptors for urokinase plasminogen activator. Fibrinolysis 2:73, 1988.CrossRefGoogle Scholar
  32. 32.
    Gurewich V, Pannell R, Louie S, Kelley P, Suddith L, Greenlee R. Effective and fibrin-specific clot-lysis by a zymogen precursor form of urokinase (pro-urokinase): A study in vitro and in two animal species. J Clin Invest 73:1731, 1984.PubMedCrossRefGoogle Scholar
  33. 33.
    Booyse FM, Lin PH, Traylor M, Bruce R. Purification and properties of a single-chain urokinase-type plasminogen activator form produced by subcultured human umbilical vein endotbehal cells. J Biol Chem 263:15139, 1988.PubMedGoogle Scholar
  34. 34.
    Gurewich V. Fibrinolytic properties of single-chain urokinase plasminogen activator and how they complement those of tissue plasminogen activator. In Haber E, Braunwald E (eds). Thrombolysis. Basic Contributions and Clinical Progress. St. Louis, MO; Mosby Year Book, 1991:51.Google Scholar
  35. 35.
    Takada A, Sugawara Y, Takada Y. Enhancement ot the activation of Glu-plasminogen by urokinase in the si multaneous presence of tranexamic acid or fibrin. Haemostasis 1:26, 1989.Google Scholar
  36. 36.
    Liu J, Gurewich V. A comparative study of the promotion of tissue plasminogen activator and pro-urokinase-induced plasminogen activation by fragments D and E-2 of fibrin. J Clin Invest 88:2012, 1991.PubMedGoogle Scholar
  37. 37.
    Pannell R, Gurewich V. Activation of plasminogen by single-chain urokinase or by two-chain urokinase — a demonstration that single-chain urokinase has a low catalytic activity (pro-urokinase). Blood 69:22, 1987.PubMedGoogle Scholar
  38. 38.
    Lenich C, Pannell R, Gurewich V. The effect of the carboxy-terminal lysine of urokinase on the catalysis of plasminogen activation. Thromb Res 64:69, 1991.PubMedCrossRefGoogle Scholar
  39. 39.
    Longstaff C, Clough AM, Gaffney PJ. Kinetics of plasmin activation of single chain urinary-type plasminogen activator (scu-PA) and demonstration of a high affinity interaction between scu-PA and plasminogen. J Biol Chem 267:173, 1992.PubMedGoogle Scholar
  40. 40.
    Ellis V, Scully MF, Kakkar VV. Plasminogen activation by single-chain urokinase in functional isolation. J Biol Chem 262:14998, 1987.PubMedGoogle Scholar
  41. 41.
    Petersen LC, Lund LR, Nielsen LS, Dano K, Skriver L. One-chain urokinase-type plasminogen activator from human sarcoma cells is a proenzyme with little or no intrinsic activity. J Biol Chem 263:11189, 1988.PubMedGoogle Scholar
  42. 42.
    Giorgetti C, Molinari A, Bonomini L, Lansen J, Gurewich V. The role of urokinase generation during clot lysis by pro-urokinase in a plasma milieu. Fibrinolysis 7:183, 1993.CrossRefGoogle Scholar
  43. 43.
    Koster RW, Cohen AF, Hopkins GR, Beier H, Gunzler WA, van der Wouw PA. Pharmacokinetics and pharmacodynamics of saruplase, an unglycosylated single-chain urokinase-type plasminogen activator, in patients with acute myocardial infarction. Thromb Haemost 72:740, 1994.PubMedGoogle Scholar
  44. 44.
    Lijnen HR, Van Hoef B, De Cock F, Collen D. The mechanism of plasminogen activation and fibrin dissolution by single-chain urokinase-type plasminogen activator in a plasma milieu in vitro. Blood 73:1864, 1989.PubMedGoogle Scholar
  45. 45.
    Lijnen HR, Nelles L, Van Hoef B, Demarsin E, Collen D. Structural and functional characterization of mutants of recombinant single-chain urokinase-type plasminogen activator obtained by site-specific mutagenesis of Lysl 58, llel 59 and Ilel60. Eur J Biochem 177:575, 1988.PubMedCrossRefGoogle Scholar
  46. 46.
    Loza J, Gurewich V, Johnstone M, Pannell R. Platelet-bound prekallikrein promotes pro-urokinase-induced clot lysis: A mechanism for targeting the factor XII dependent intrinsic pathway of fibrinolysis. Thromb Haemost 71:347, 1994.PubMedGoogle Scholar
  47. 47.
    Edelberg JM, Weissler M, Pizzo SV. Kinetic analysis of the effects of glycosaminoglycans and lipoproteins on urokinase-mediated plasminogen activation. Biochem J 276:785, 1991.PubMedGoogle Scholar
  48. 48.
    de Munk GAW, Groeneveld E, Rijken DC. Acceleration of the thrombin inactivation of single chain urokinase-type plasminogen activator (pro-urokinase) by thrombomodulin. J Clin Invest 88:1680, 1991.PubMedGoogle Scholar
  49. 49.
    van de Werf F, Vanhaecke J, de Geest H, Verstraete M, Collen D. Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction. Circulation 74:1066, 1986.PubMedGoogle Scholar
  50. 50.
    Gulba DC, Fischer K, Bartheis M, Polensky U, Reil G-H, Daniel WG, Welzel D, Lichtlen PR. Low dose urokinase preactivated natural pro-urokinase for thrombolysis in acute myocardial infarction. Am J Cardiol 63:1025, 1989.PubMedCrossRefGoogle Scholar
  51. 51.
    Collen D, De Cock F, Lijnen HR. Biological and thrombolytic properties of proenzyme and active forms of human urokinase. II. Turnover of natural and recombinant urokinase in rabbits and squirrel monkeys. Thromb Haemost 52:24, 1984.PubMedGoogle Scholar
  52. 52.
    Kohler M, Sen S, Miyashita C, Hermes R, Pindur G, Heiden M, Berg G, Morsdorf S, Leipnitz G, Zeppezauer M, Schieffer H, Wenzel E, Schonberger A. Hollemeyer K. Half-life of single-chain urokinase-type plasminogen activator (scu-PA) and two-chain urokinase-type plasminogen activator (tcu-PA) in patients with acute myocardial infarction. Thromb Res 62:75, 1991.PubMedCrossRefGoogle Scholar
  53. 53.
    Kasper W, Hohnloser SH, Engler H, Meinertz T, Wilkens J, Roth E, Lang K, Limbourg P, Just H. Coronary reperfusion studies with pro-urokinase in acute myocardial infarction: Evidence for synergism of low dose urokinase. J Am Coll Cardiol 16:733, 1990.PubMedGoogle Scholar
  54. 54.
    Bode C, Schuler G, Nordt T, SchÖnermark S, Baumann H, Richardt G, Dietz R, Gurewich V, Kubier W. Intravenous thrombolytic therapy with a combination of single-chain urokinase-type plasminogen activator and recombinant tissue-type activator in acute myocardial infarction. Circulation 81:907, 1990.PubMedGoogle Scholar
  55. 55.
    Kirshenbaum JM, Bahr RD, Flaherty JT, Gurewich V, Levine HJ, Loscalzo J, Schumacher RR, Topol EJ, Wahr D, Braunwald E. Clot-selective coronary thrombolysis with low-dose synergistic combinations of single-chain urokinase-type plasminogen activator and recombinant tissue-type plasminogen activator. The Pro-Urokinase for Myocardial Infarction Study Group. Am J Cardiol 68:1564, 1991.PubMedCrossRefGoogle Scholar
  56. 56.
    Zarich SW, Kowalchuk GJ, Weaver WD, Loscalzo J, Sasower M, Manzo K, Byrnes C, Muller JE, Gurewich V for the PATENT Study Group. Sequential combination thrombolytic therapy for acute myocardial infarction: Results of the Pro-urokinase and t-PA enhancement of thrombolysis (PATENT) trial. J Am Coll Cardiol 26:374, 1995.PubMedCrossRefGoogle Scholar
  57. 57.
    Bode C, SchÖnermark S, Schuler G, Zimmermann R, Schwarz F, Kubier W. Efficacy of intravenous pro-urokinase and a combination of pro-urokinase and urokinase in acute myocardial infarction. Am J Cardiol 61:971–974, 1988.PubMedCrossRefGoogle Scholar
  58. 58.
    Loscalzo J, Wharton T, Kirshenbaum JM, Levine HJ, Flaherty JT, Topol EJ, Ramaswamy K, Kosowsky BD, Salem DN, Ganz P, Brinker JA, Gurewich V, Muller JE, and the Pro-Urokinase for Myocardial Infarction Study Group. Clot-selective coronary thrombolysis with pro-urokinase, Circulation 79:776, 1989.PubMedGoogle Scholar
  59. 59.
    Gulba DC, Bode C, Sen S, Topp J, Fischer K, Wolf H, Hecker H and the German Preactivated Pro-Urokinasc Study Group. Multicenter dose-finding trial for thrombolysis with urokinase preactivated pro-urokinase (TCL 598) in acute myocardial infarction. Cathet Cardiovasc Diagn 26:177, 1992.PubMedCrossRefGoogle Scholar
  60. 60.
    PRIMI Trial Study Group. Randomized double-blind trial of recombinant pro-urokinase against streptokinase in acute myocardial infarction. Lancet 1:863, 1989.Google Scholar
  61. 61.
    Diefenbach C, Erbel R, Pop T, Mathey D, Schofer J, Hamm C, Ostermann H, Schmitz-Hübner U, Bleifeld W, Meyer J. Recombinant single-chain urokinase-type plasminogen activator during acute myocardial infarction. Am J Cardiol 61:966, 1988.PubMedCrossRefGoogle Scholar
  62. 62.
    Tebbe U, Windeier J, Boesel I, Hoffmann H, Wojcik J, Ashmawy M, Schwarz ER, von Loewis of Menar P, Roesmeyer P, Hopkins G, Barth H, on behalf of the LIMITS Study Group. Thrombolysis with recombinant unglycosylated single-chain urokinase-type plasminogen activator (Saruplase) in acute myocardial infarction: Influence of heparin on early patency rate (LIMITS Study). J Am Coll Cardiol 26:365, 1995.PubMedCrossRefGoogle Scholar
  63. 63.
    Weaver WD, Hartmann JR, Anderson JL, Reddy PS, Sobolski JC, Sasahara AA. New recombinant glycosylated prourokinase for treatment of patients with acute myocardial infarction. Prourokinase Study Group. J Am Coll Cardiol 24:1242, 1994.PubMedGoogle Scholar
  64. 64.
    Gulba DC, Fischer K, Bartheis M, Jost S, Moller W, Frombach R, Reil G-H, Daniel WG, Lichtlen PR. Potentiative effect of heparin in chrombolytic therapy of evolving myocardial infarction with natural pro-urokinase. Fibrinolysis 3:165, 1989.CrossRefGoogle Scholar
  65. 65.
    Gulba DC, Bode C, Runge MS, Huber K. Thrombolytic agents — an overview. Ann Haematol 73:S9, 1996.Google Scholar
  66. 66.
    Ostermann H, U.S-H, Windeler J, Bar F, Meyer J, van de Loo J. Rate of fibrinogen breakdown related to coronary patency and bleeding complications in patients with thrombolysis in acute myocatdial infarction — results from the PRIMI trial. Eur Heart J 13:1225, 1992.PubMedGoogle Scholar
  67. 67.
    TIMI Study Group. The thrombolysis in myocardial infarction (TIMI) trial: Phase I findings. N Engl J Med 312:932, 1985.Google Scholar
  68. 68.
    Kambara H, Kawai C, Kajiwara N, Nitani H, Sasayama S, Kanmatsuse K, Kodama K, Sato H, Nobuyoshi M, Nakashima M, Matsuo O, Matsuda T. Randomized, double-blinded multicenter study: Comparison of intracoronary single-chain urokinase-type plasminogen activator, pro-urokinase (GE-0943), and intracoronary urokinase in parients with acute myocardial infarction. Circulation 78:899, 1988.PubMedGoogle Scholar
  69. 69.
    Pindur G, Koehler M, Sen S, Hermes R, Miyashita C, Wenzel E, Schieffer H. Fibrinolytic effects of pro-urokinase combined with low-dose urokinase compared to high-dose urokinase in patients with acute myocardial infarction. Thromb Res 67:191, 1992.PubMedCrossRefGoogle Scholar
  70. 70.
    Schofer J, Lins M, Mathey DG, Sheehan FH. Time course of left ventricular function and coronary patency after saruplase vs. streptokinase in acute myocardial infarction. The PRIMI Trial Study Group. Eur Heart J 14:958, 1993.PubMedGoogle Scholar
  71. 71.
    Vogt A, von Essen R, Tebbe U, Feuerer W, Appel KF, Neuhaus KL. Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: Retrospective analysis of four German multicenter studies. J Am Coll Cardiol 21:1391, 1993.PubMedCrossRefGoogle Scholar
  72. 72.
    Huber K, Kirchheimer JC, Binder BR. Rapid isolation of high molecular weight urokinase from native human urine. Thromb Haemost 47:197, 1982.PubMedGoogle Scholar
  73. 73.
    Husain SS, Gurewich V, Lipinski B. Purification and partial characterization of a single-chain-high-molecular-weight form of urokinase from human urine. Arch Biochem Biophys 220:31, 1982.CrossRefGoogle Scholar
  74. 74.
    Barlow GH, Lazer L, Rueter A, Tribby I. Production of plasminogen activators by culture cell techniques. In Paoletti R, Sherry S (eds). New York: Academic Press. 1977:758.Google Scholar
  75. 75.
    Harpel PC, Chang T-S, Verderber E. Tissue-plasminogen activator and urokinase mediate the binding of glu-plasminogen to plasma fibrin. I. Evidence for new binding sites in plasma-degraded fibrin. J Biol Chem 260:4432, 1985.PubMedGoogle Scholar
  76. 76.
    van de Loo JCW, Kriessmann A, Trübestein G, Knoch K, de Swart CAM, Asbeck F, Marbert GA, Schmitt HE, Seweil AF, Ducken F, Theiss W, Ritz R. Controlled multicenter pilot study of urokinase-hepann and streptokinase in deep vein thrombosis. Thromb Haemost 50:660, 1983.PubMedGoogle Scholar
  77. 77.
    Neuhaus KL, Tebbe U, Gottwik M, Weber MAJ, Feuerer W, Niederer W, Haerer W, Praetorius F, Grosser K-D, Huhmann W, Hoepp H-W, Alber G, Sheikhzadeh A, Schneider B. Intravenous recombinant tissue plasminogen activator (rt-PA) and urokinase in acute myocardial infarcrion: Results of the German activator urokinase study (GAUS). J Am Coll Cardiol 12:581, 1988.PubMedGoogle Scholar
  78. 78.
    Goldhaber SZ, Kessler CM, Heit J, Markis J, Sharma GVRK, Dawley D, Nagel JS, Meyerovitz M, Kim D, Vaughan DE, Parker JA, Tumeh SS, Drum D, Loscalzo J, Reagan K, Selwyn AP, Anderson J, Braunwald E. Randomized controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism. Lancet 2:293, 1988.PubMedCrossRefGoogle Scholar
  79. 79.
    Fletcher AP, Alkjaersig N, Sherry S, Genton E, Hirsh J, Bachmann F. The development of urokinase as a thrombolytic agent: Maintenance of a sustained thrombolytic state in man by its intravenous infusion. J Lab Clin Med 65:713, 1965.PubMedGoogle Scholar
  80. 80.
    Gulba DC, Lichtlen PR. Urokinasetherapie bei thromboembolischen Erkrankungen. In Kirchhof B, Kienast J (eds). Thrombolysetherapie: Daten und Argumente fur verschiedenen Verfahren und Substanzen. Emmendingen: Kesselring, 1988:45.Google Scholar
  81. 81.
    Mathey DG, Schofer H, Sheehan FH, Becher H, Tilsner V, Dodge HT. Intravenous urokinase in acute myocardial infarction. Am J Cardiol 55:878, 1985.PubMedCrossRefGoogle Scholar
  82. 82.
    Lincoff AM, Topol EJ. Thrombolytic therapy. In Fuster V, Ross R, Topol EJ (eds). Arherosderosis and Coronary Artery Disease. Philadelphia: Lippincott-Raven, 1996:955.Google Scholar
  83. 83.
    Popma JJ, Califf RM, Ellis SG, George BS, Kereiakes DJ, Samaha JK, Worley SJ, Anderson JL, Stump D, Woodlief L, Sigmon K, Wall TC, Topol EJ. Mechanism of benefit of combination thrombolytic therapy for acute myocardial infarction: A quantitative angiographic and hematologie study. J Am Coll Cardiol 20:1305, 1992.PubMedGoogle Scholar
  84. 84.
    Leschke M, Schoebel F-C, Mecklenbeck W, Stein D, Jax TW, Miiller-Gcärtner H-W, Strauer B-E. Long-term intermittent urokinase therapy in patients with end-stage coronary artery disease and refractory angina pectoris: A randomized dose-response trial. J Am Coll Cardiol 27:575, 1996.PubMedCrossRefGoogle Scholar
  85. 85.
    Gaffney PJ, Heath AB. A collaborative study to establish a standard for high molecular weight urinary-type plasminogen activator (HMW/u-PA). Thromb Haemost 64:398, 1990.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Kurt Huber

There are no affiliations available

Personalised recommendations