tPA and scuPA: New Concepts in the Treatment of Acute Stroke

  • G. J. Del Zoppo


Recombinant DNA techniques have allowed the synthesis of two relatively thrombus-specific thrombolytic enzymes, tissue plasminogen activator (tPA) and single- chain urokinase plasminogen activator (scuPA, pro-urokinase), in quantities sufficient for clinical studies. The possible use of these interesting proteins in the treatment of acute thromboembolic stroke is the subject of this review. The hypothesis that is central to the possible use of these agents is that neurological function may be preserved and ischemic injury reduced if agents which produce dissolution of thrombi are given early in the course of acute thrombotic stroke [1]. Recent experience with local infusion of the conventional thrombolytic agents urokinase and streptokinase imply that fibrin-specific agents may have value in the treatment of acute stroke. The theoretical basis for the use of these agents follows directly from the molecular mechanisms of endogenous thrombolysis.


Acute Stroke Thrombolytic Therapy Thrombolytic Agent Fibrinolytic Agent Intracoronary Streptokinase 
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.


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  1. 1.
    del Zoppo GJ, Zeumer H, Harker LA (1986) Thrombolytic therapy in acute stroke: Possibilities and hazards. Stroke 17: 595–607PubMedCrossRefGoogle Scholar
  2. 2.
    Kakkar W, Scully MF (1978) Thrombolytic therapy. Br Med Bull 34: 191–199PubMedGoogle Scholar
  3. 3.
    Sharma GVRK, Cella G, Parish AF, Sasahara AA (1982) Drug therapy: thrombolytic therapy. N Engl J Med 306: 1268–1276PubMedCrossRefGoogle Scholar
  4. 4.
    Verstraete M (1978) Biochemical and clinical aspects of thrombolysis. Semin Hematol 15: 35–54PubMedGoogle Scholar
  5. 5.
    Bachmann F, Kruithof IEKO (1984) Tissue plasminogen activator: chemical and physiological aspects. Semin Thromb Hemost 10: 6–17PubMedCrossRefGoogle Scholar
  6. 6.
    Collen D, Lijnen HR (1984) New approaches to thrombolytic therapy. Arteriosclerosis 4: 579–585PubMedCrossRefGoogle Scholar
  7. 7.
    Verstraete M, Collen D (1986) Thrombolytic therapy in the eighties. Blood 67: 1529–1541PubMedGoogle Scholar
  8. 8.
    Thompson AR, Harker LA (1983) Manual of hemostasis and thrombosis. Davis, Philadelphia, pp 41–45Google Scholar
  9. 9.
    Kaplan AP (1978) Initiation of the intrinsic coagulation and fibrinolytic pathways of man: the role of surfaces, Hageman factor, prekallikrein, high molecular weight kininogen, and factor XI. Prog Hemost Thromb 4: 127PubMedGoogle Scholar
  10. 10.
    Hermans J, McDonagh J (1982) Fibrin: structure and interactions. Semin Thromb Hemost 8: 11–24PubMedCrossRefGoogle Scholar
  11. 11.
    Castellino FJ (1984) Biochemistry of human plasminogen. Semin Thromb Hemost 10: 18–23Google Scholar
  12. 12.
    Walsh P, Greenspan RH, Simon AL (1978) Urokinase-pulmonary embolism trial. Circulation 67 (suppl):l–108Google Scholar
  13. 13.
    Urokinase Streptokinase Embolism Trial (1974) JAMA 16: 1606–1613Google Scholar
  14. 14.
    Dotter CT, Seaman AJ (1974) Clot lysis with low-dose streptokinase. Radiology 111: 31–37PubMedGoogle Scholar
  15. 15.
    Katzen BT, van Breda A (1981) Low dose streptokinase in the treatment of arterial occlusions. Am J Radiol 136: 1171–1181Google Scholar
  16. 16.
    Hess H, Ingrisch H, Mietaschk A, Rath H (1982) Local low-dose thrombolytic therapy of peripheral arterial occlusions. N Engl J Med 307: 1627–1630PubMedCrossRefGoogle Scholar
  17. 17.
    Verstraete M (1972) Thrombolytic treatment of recent arterial occlusion. J Clin Pathol 25: 641–642PubMedCrossRefGoogle Scholar
  18. 18.
    Poliwoda H, Alexander K, Buhl V, Holsten D, Wagner HH (1969) Treatment of chronic arterial occlusions with streptokinase. N Engl J Med 280: 689–692PubMedCrossRefGoogle Scholar
  19. 19.
    Hume M, Gurewich V, Thomas DP, Dealy Jr JB (1970) Streptokinase for chronic arterial occlusive disease. Arch Surg 101: 653–657PubMedGoogle Scholar
  20. 20.
    Poliwoda H (1972) Treatment of chronic arterial occlusions with streptokinase. J Clin Pathol 27: 642–643CrossRefGoogle Scholar
  21. 21.
    Reichle FA, Rao NS, Chang KHY, Marder V, Algazy K (1977) Thrombolysis of acute or subacute non-embolic arterial thrombosis. J Surg Res 22: 202–208PubMedCrossRefGoogle Scholar
  22. 22.
    Martin M, Roth F-J, Fiebach BJO, Auel H (1978) Fibrinolytische Therapie mit Aktivator. Dtsch Med Wochenschr 103: 1953–1957PubMedCrossRefGoogle Scholar
  23. 23.
    Martin M, Auel H (1979) Thrombolytic therapy in arterial thromboembolism. Prog Cardiovasc Dis XXI (5): 351–374PubMedCrossRefGoogle Scholar
  24. 24.
    Rentrop P, Blanke H, Weigand V, Karsch KR (1979) Wiederoffnung verschlossener Kranzgefafle im akuten Infarkt mit Hilfe von Kathetern ( Transluminale Rekanalisation ). Dtsch Med Wochenschr 104: 1401Google Scholar
  25. 25.
    Rentrop P, Blanke H, Karsch KR, Kaeser H, Kostering H, Leitz K (1981) Selective intracoronary thrombolysis in acute myocardial infarction and unstable angina pectoris. Circulation 63: 307–317PubMedCrossRefGoogle Scholar
  26. 26.
    Mathey DG, Kuck K-H, Tilsner V, Krebber H-J, Bleifeld W (1981) Nonsurgical coronary artery recanalization in acute transmural myocardial infarction. Circulation 63: 489–497PubMedCrossRefGoogle Scholar
  27. 27.
    Ganz W, Buchbinder N, Marcus H, Mondkar A, Maddahi J, Chruzi Y, O’Connor L, Shell W, Fishbein MC, Kass R, Miyamoto A, Swan JHC (1981) Intracoronary thrombolysis in evolving myocardial infarction. Am Heart J 101: 4–13PubMedCrossRefGoogle Scholar
  28. 28.
    Cowley MJA, Hastillo A, Vetrovec GW, Hess ML (1981) Effects of intracoronary streptokinase in acute myocardial infarction. Am Heart J 10: 1149–1158CrossRefGoogle Scholar
  29. 29.
    Neuhaus KL, Tebbe U, Sauer G, Rahlf G, Kostering H, Kreuzer K (1981) High-dose i.v. streptokinase infusion in acute myocardial infarction. Eur Heart J 2: 144Google Scholar
  30. 30.
    Rutsch W, Schartl M, Mathey D, Kuck K, Merx W, Dorr R, Rentrop P, Blanke H (1981) Percutaneous transluminal coronary recanalization: Procedure, results, and acute complications. Am Heart J 102: 1178–1181Google Scholar
  31. 31.
    Ganz W, Geft I, Maddahi J, Berman D, Charuzi Y, Shah PK, Swan HJC (1983) Non-surgical reperfusion in evolving myocardial infarction. J Am Coll Cardiol 1: 1247–1253PubMedCrossRefGoogle Scholar
  32. 32.
    Timmis GC, Gangadharan V, Hauser AM, Ramos RG, Westveer DC, Gordon S (1982) Intracoronary streptokinase in clinical practice. Am Heart J 104: 925–938PubMedCrossRefGoogle Scholar
  33. 33.
    Smalling RW, Fuentes F, Freund GC, Reduto LA, Wanta-Matthews M, Gaeta JM, Walker W, Sterling R, Gould KL (1982) Beneficial effects of intracoronary thrombolysis up to eighteen hours after onset of pain in evolving myocardial infarction. Am Heart J 104: 912–920PubMedCrossRefGoogle Scholar
  34. 34.
    Khaja F, Walton Jr JA, Brymer JF, Lo E, Osterberger L, O’Neil WW, Colfer HT, Weiss R, Lee T, Kurian T, Goldberg AD, Pitt B, Goldstein S (1983) Intracoronary fibrinolytic therapy in acute myocardial infarction. N Engl J Med 308: 1305–1311PubMedCrossRefGoogle Scholar
  35. 35.
    Anderson JL, Marshall HW, Bray BE, Lutz JR, Frederick PR, Yanowitz FG, Datz FL, Klausner SC, Hagan AD (1983) A randomized trial of intracoronary streptokinase in the treatment of acute myocardial infarction. N Engl J Med 308: 1312–1318PubMedCrossRefGoogle Scholar
  36. 36.
    Kennedy JW, Ritchie JL, Davis KB, Fritz JK (1983) Western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction. N Engl J Med 309: 1477–1482PubMedCrossRefGoogle Scholar
  37. 37.
    Leiboff RH, Katz RJ, Wasserman AG, Bren GB, Schwartz H, Varghese J, Ross AM (1984) A randomized, angiographically controlled trial of intracoronary streptokinase in acute myocardial infarction. Am J Cardiol 53: 404–407PubMedCrossRefGoogle Scholar
  38. 38.
    Schroeder R, Biamino G, Leitner E-R, Linderer T, Bruggemann T, Heitz J, Vohringer H-F, Wegscheider K (1983) Intravenous short-term infusion of streptokinase in acute myocardial infarction. Circulation 67: 536–548CrossRefGoogle Scholar
  39. 39.
    Spann JF, Sherry S, Carabello BA, Denenberg BS, Mann RH, McCann WD, Gault JH, Gentzler RD, Belber AD, Maurer AH, Copper EM (1984) Coronary thrombolysis by intravenous streptokinase in acute myocardial infarction: acute and follow-up studies. Am J Cardiol 53: 655–661PubMedCrossRefGoogle Scholar
  40. 40.
    European Cooperative Study Group (1979) Streptokinase in acute myocardial infarction. N Engl J Med 301: 797–802CrossRefGoogle Scholar
  41. 41.
    TIMI Study Group (1985) Special report: The thrombolysis in myocardial infarction (TIMI) trial. N Engl J Med 312: 932–936Google Scholar
  42. 42.
    Aber CP, Bass NM, Berry CL, Carson PHM, Dobbs RJ, Fox KM, Hamblin JJ, Haydu SP, Howitt G, Maclver JE, Portal RW, Raftery EB, Rousell RH, Stock JPP (1976) Streptokinase in acute myocardial infarction: a controlled multicentre study in the United Kingdom. Br Med J 2: 1100–1104PubMedCrossRefGoogle Scholar
  43. 43.
    Robertson BR, Nilsson IM, Nylander G, Olow B (1967) Effect of streptokinase and heparin on patients with deep venous thrombosis. Acta Chir Scand 133: 205–215PubMedGoogle Scholar
  44. 44.
    Robertson BR, Nilsson IM, Nylander G (1968) Value of streptokinase and heparin in treatment of acute deep venous thrombosis. Acta Chir Scand 134: 203–208PubMedGoogle Scholar
  45. 45.
    Kakkar VV, Flanc C, O’Shea MJ, Flute PT, Howe CT, Clarke MB (1969) Treatment of deep-vein thrombosis with streptokinase. Br J Surg 56: 178–183PubMedCrossRefGoogle Scholar
  46. 46.
    Mavor GE, Bennett B, Galloway JMD, Karmody AM (1969) Streptokinase in iliofemoral venous thrombosis. Br J Surg 56: 564–570PubMedCrossRefGoogle Scholar
  47. 47.
    Mavor GE, Dhall DP, Dawson AA, Duthie JS, Walker MG, Mahaffy RG, Allardyce M (1973) Streptokinase therapy in deep-vein thrombosis. Br J Surg 60: 468–474PubMedCrossRefGoogle Scholar
  48. 48.
    Tsapogas MJ, Peabody RA, Wu KT, Karmody AM, Devaraj KT, Eckert C (1973) Controlled study of thrombolytic therapy in deep vein thrombosis. Surgery 74: 973–984PubMedGoogle Scholar
  49. 49.
    Astedt B, Robertson B, Haeger K (1974) Experience with standardized streptokinase therapy of depp venous thrombosis. Surg Gynecol Obstet 139: 387–388PubMedGoogle Scholar
  50. 50.
    Chavatzas D, Martin P (1975) A study of streptokinase in deep vein thrombosis of the lower extremities. Vasa 4: 68–72PubMedGoogle Scholar
  51. 51.
    Duckert F, Muller G, Nyman D, Benz A, Prisender S, Madar G, Da Silva MA, Widmer LK, Schmitt HE (1975) Treatment of deep vein thrombosis with streptokinase. Br Med J 1: 479–481PubMedCrossRefGoogle Scholar
  52. 52.
    Kakkar VV, Lewis M, Sagar S (1975) Treatment of deep-vein thrombosis with intermittent streptokinase and plasminogen infusion. Lancet i: 674–676Google Scholar
  53. 53.
    Marder VJ, Loulen RL, Atichartakarn V, Budzynski AZ, Parulekar S, Kim JR, Edward N, Zahavi J, Algazy KM (1977) Quantitative venographic assessment of deep vein thrombosis in the evaluation of streptokinase and heparin therapy. J Lab Clin Med 89: 1018–1029PubMedGoogle Scholar
  54. 54.
    Seaman AJ, Common HH, Rosch J, Dotter CT, Porter JM, Lindell TD, Lawler WL, Schlueter WJ (1976) Deep vein thrombosis treated with streptokinase or heparin: a randomized study. Angiology 27: 549–556PubMedCrossRefGoogle Scholar
  55. 55.
    Bieger R, Boekhout-Mussert RJ, Hohmann F, Loeliger EA (1976) Is streptokinase useful in the treatment of deep vein thrombosis? Acta Med Scand 199: 81–88PubMedCrossRefGoogle Scholar
  56. 56.
    Arnesen H, Heilo A, Jakobsen E, Ly B, Skaga E (1978) A prospective study of streptokinase and heparin in the treatment of deep vein thrombosis. Acta Med Scand 203: 457–463PubMedCrossRefGoogle Scholar
  57. 57.
    Jarvinen P, Aromaa U, Roiha M, Asp K (1978) Streptokinase and concomitant oral anticoagulants in the treatment of deep venous thrombosis. Klin Wochenschr 56: 801–804PubMedCrossRefGoogle Scholar
  58. 58.
    Marbet GA, Eichlisberger R, Duckert F, de Silva MA, Biland L, Widmer LK, Ritz R, Schmitt HE (1982) Sequential treatment of deep leg vein thrombosis with porcine plasmin and low dose streptokinase. Thromb Haemost 48: 190–195Google Scholar
  59. 59.
    Schulman S, Lockner D, Granqvist S, Bratt G, Paul C, Nyman D (1984) A comparative randomized trial of low-dose versus high-dose streptokinase in deep vein thrombosis of the thigh. Thromb Haemost 51: 261–265PubMedGoogle Scholar
  60. 60.
    Trubestein G (1984) Indikation und Durchfuhrung der fibrinolytischen Therapie mit Streptokinase und Urokinase bei tiefer Venenthrombose. Vasa (Suppl) 12: 104–113Google Scholar
  61. 61.
    Serradimigni A, Bory M, Dijiane P, Mathieu P, Leonetti J, Juhan-Vague I, Sampol J (1978) Treatment of venous thrombosis and pulmonary embolism by streptokinase. Angiology 29: 825–831PubMedCrossRefGoogle Scholar
  62. 62.
    Sherry S (1985) Tissue plasminogen activator (t-PA): will it fulfill its promise? N Engl J Med 313: 1014–1017PubMedCrossRefGoogle Scholar
  63. 63.
    Marder VJ (1986) Fibrinolytic agents: are they feasible for stroke therapy? In: Plum F, Pulsinelli WA (eds) Cerebrovascular diseases, fourteenth research conference. Raven, New York, pp 241–247Google Scholar
  64. 64.
    Cercek B, Lew AS, Hod H, Yano J, Reddy NKN, Ganz W (1986) Enhancement of thrombolysis with tissue-type plasminogen activator by pretreatment with heparin. Circulation 74: 583–587PubMedCrossRefGoogle Scholar
  65. 65.
    Solis OJ, Roberson GR, Taveras JM, Mohr J, Pessin MS (1977) Cerebral angiography in acute cerebral infarction. Revist Interam Radiol 2: 19–25Google Scholar
  66. 66.
    Clarke RL, Cliffton EE (1960) The treatment of cerebrovascular thrombosis and embolism with fibrinolytic agents. Am J Cardiol 30: 546–551CrossRefGoogle Scholar
  67. 67.
    Meyer JS, Herndon RM, Gotoh F, Tazaki Y, Nelson JN, Johnson JF (1961) Therapeutic thrombolysis. In: Millikan CH, Siekert RG, Whisnant JP (eds) Cerebral vascular disease, third princeton conference. Grune and Stratton, New York, pp 160–177Google Scholar
  68. 68.
    Herndon RM, Nelson JN, Johnson JF, Meyer JS (1961) Thrombolytic treatment in cerebrovascular thrombosis. In: MacMillan RL, Mustard JF (eds) Anticoagulants and fibrinolysins, Lea and Febiger, Philadelphia, pp 154–164Google Scholar
  69. 69.
    Meyer JS, Gilroy J, Barnhart ME, Johnson JF (1965) Therapeutic thrombolysis in cerebral thromboembolism: randomized evaluation of intravenous streptokinase. In: Millikan CH, Siekert RG, Whisnant JP (eds). Cerebral vascular diseases, fourth princeton conference. Grune and Stratton, New York, pp 200–213Google Scholar
  70. 70.
    Fletcher AP, Alkjaersig N, Lewis M, Tulevski V, Davies A, Brooks JE, Mardin WB, Landau WM, Raichle ME (1976) A pilot study of urokinase therapy in cerebral infarction. Stroke 7: 135–142PubMedCrossRefGoogle Scholar
  71. 71.
    Hanaway J, Torack R, Fletcher AP, Landau WM (1976) Intracranial bleeding associated with urokinase therapy for acute ischemic hemispheral stroke. Stroke 7: 143–146PubMedCrossRefGoogle Scholar
  72. 72.
    Kaufman HH, Lind TA, Clark DS (1977) Non-penetrating trauma to the carotid artery with secondary thrombosis and embolism: treatment by thrombolysin. Acta Neurochir 37: 219–244CrossRefGoogle Scholar
  73. 73.
    Atkin N, Nitzberg S, Dorsey J (1964) Lysis of intracerebral thromboembolism with fibrinolysin. Angiology 15: 436–439CrossRefGoogle Scholar
  74. 74.
    Matuso O, Kosugi T, Mihara H, Ohki Y, Matsuo T (1979) Retrospective study on the efficacy of using urokinase therapy. Acta Haematol 42: 684–688Google Scholar
  75. 75.
    Abe T, Kazawa M, Naito I (1981) Clinical effect of urokinase (60000 units/day) on cerebral infarc- tion-comparative study by means of multiple center double blind test. Blood Vessels 12: 342–358CrossRefGoogle Scholar
  76. 76.
    Abe T, Kazawa M, Naito I (1981) Clinical evaluation for efficacy of tissue culture urokinase ( TCUK) on cerebral thrombosis by means of multicenter double-blind study. Blood Vessels 12: 321–341Google Scholar
  77. 77.
    Nenci GG, Gresele P, Taramelli M, Agnelli G, Signorini E (1983) Thrombolytic therapy for thromboembolism of vertebrobasilar artery. Angiology 34: 561–571PubMedCrossRefGoogle Scholar
  78. 78.
    Miyakawa T (1984) The cerebral vessels and thrombosis. Rinsho Ketsueki 25: 1018–1026PubMedGoogle Scholar
  79. 79.
    Zeumer H (1985) Survey of progress: vascular recanalizing techniques in interventional neuroradiology. J Neurol 231: 287–294PubMedCrossRefGoogle Scholar
  80. 80.
    Bruckmann H, Ferbert A, del Zoppo GJ, Hacke W, Zeumer H (1987) The acute vertebrobasilar thrombosis: angiological-clinical comparison and therapeutic implications. Acta Radiol 369: 38–42Google Scholar
  81. 81.
    Rijken DC, Collen D (1981) Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture. J Biol Chem 256: 7035PubMedGoogle Scholar
  82. 82.
    Ranby M (1982) Tissue plasminogen activator. Isolation, enzymatic properties and assay procedure. Thesis, Umea University, Umea, Medical Dissertations New Series, no. 90: 7035Google Scholar
  83. 83.
    Zamarron C, Lijnen HR, Collen D (1984) Kinetics of the activation of plasminogen by natural and recombinant tissue-type plasminogen activator. J Biol Chem 259: 2080–2083PubMedGoogle Scholar
  84. 84.
    Pennica D, Holmes WE, Kohr WJ, Harkins RN, Vehar GA, Ward CA, Bennett WF, Yelverton E, Seeburg PH, Heyneker HL, Goeddel DV, Collen D (1983) Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature 301: 214Google Scholar
  85. 85.
    Strassburger W, Wollmer A, Pitts JE, Glover ID, Tickle IJ, Blundell TL, Steffens GJ, Gunzler WA, Otting F, Flohe L (1983) Adaptation of plasminogen activator sequences to known protease structures. FEBS Lett 157: 219PubMedCrossRefGoogle Scholar
  86. 86.
    Rijken DC, Hoylaerts M, Collen D (1982) Fibrinolytic properties of one-chain and two-chain human extrinsic (tissue-type) plasminogen activator. J Biol Chem 257: 2920PubMedGoogle Scholar
  87. 87.
    Ranby M, Bergsdorf N, Nilsson T (1982) Enzymatic properties of the one- and two-chain form of tissue plasminogen activator. Thromb Res 27: 175PubMedCrossRefGoogle Scholar
  88. 88.
    Collen D, Stassen JM, Marafino Jr BJ, Buildeo S, de Cock F, Ogez J, Tajiri D, Pennica D, Bennett WF, Saliva J, Hoyng CF (1984) Biological properties of human tissue-type plasminogen activator obtained by expression of recombinant DNA in mammalian cells. J Physiol Exp Ther 231: 146–152Google Scholar
  89. 89.
    Bergmann SR, Fox KAA, Ter-Pogossian MM, Sobel BE, Collen D (1983) Clot-selective coronary thrombolysis with tissue-type plasminogen activator. Science 220: 1181–1183PubMedCrossRefGoogle Scholar
  90. 90.
    Goldhaber SZ, Vaughan DE, Markis JE, Selwyn AP, Meyerovitz M, Loscalzo J, Dawley DL, Sharma GVRK, Sasahara A, Grossbard EB, Braunwald E (1986) Efficacy and safety of tissue plasminogen activator in treatment of acute pulmonary embolism. In: VHIthe international congress on fibrinolysis, WienGoogle Scholar
  91. 91.
    Gunzler WA, Steffens GJ, Otting F, Kim SMA, Frankus E, Flohe L (1982) The primary structure of high molecular mass urokinase from human urine. Hoppe-Seyler’s Z Physiol Chem 363: 1155–1165PubMedCrossRefGoogle Scholar
  92. 92.
    Husain S, Gurewich V, Lipinski B (1983) Purification and partial characterization of a single- chain high-molecular-weight form of urokinase from human urine. Arch Biochem Biophys 220: 31PubMedCrossRefGoogle Scholar
  93. 93.
    Collen D, Zamarron C, Lijnen HR, Hoylaerts M (1986) Activation of plasminogen by pro- urokinase. II. Kinetics. J Biol Chem 261: 1253Google Scholar
  94. 94.
    Zamarron C, Lijnen HR, Van Hoef B, Collen D (1984) Biological and thrombolytic properties of proenzyme and active forms of human urokinase. I. Fibrinolytic and fibrinogenolytic properties in human plasma in vitro of urokinase obtained from human urine or by recombinant DNA technology. Thromb Haemost 52: 19Google Scholar
  95. 95.
    Lijnen HR, Zamarron C, Collen D (1985) Pro-urokinase: kinetics and mechanism of action. Thromb Haemost 54 (suppl 1): 118Google Scholar
  96. 96.
    Collen D, Stump D, Van de Werf F, Jang IK, Nobuhara M, Lijnen HR (1985) Coronary thrombolysis in dogs with intravenously administered human pro-urokinase. Circulation 72: 384Google Scholar
  97. 97.
    Collen D (1986) Human tissue-type plasminogen activator (t-PA) and single chain urokinase- type plasminogen activator (scu-PA) act synergically on clot lysis in vivo but not in vitro. In: Vlllth international congress on fibrinolysis, WienGoogle Scholar
  98. 98.
    Hornig CR, Dorndorf W, Agnoli AL (1986) Hemorrhagic cerebral infarction: a prospective study. Stroke 17: 179–185PubMedCrossRefGoogle Scholar
  99. 99.
    Mohr JP, Caplan LR, Melski JW, Golstein RJ, Duncan GW, Kistler JP, Pessin MS, Bleich HL (1978) The Harvard Cooperative Stroke registry: a prospective registry. Neurology 28: 754–762PubMedGoogle Scholar
  100. 100.
    Aring CD, Merritt HH (1935) Differential diagnosis between cerebral hemorrhage and cerebral thrombosis. Arch Intern Med 56: 435–456Google Scholar
  101. 101.
    Whisnant JP, Fitzgibbons JP, Kurland LT (1971) Natural history of stroke in Rochester, Minnesota, 1945 through 1954. Stroke 2: 11–22PubMedCrossRefGoogle Scholar
  102. 102.
    Matsumoto N, Whisnant JP, Kurland LT (1973) Natural history of stroke in Rochester, Minnesota, 1955 through 1969: an extension of previous study, 1945 through 1954. Stroke 4: 20–29PubMedCrossRefGoogle Scholar
  103. 103.
    Kannel WB, Dawber TR, Cohen MS (1973) Vascular disease of the brain - epidemiologic aspects: the Framingham study. Am J Public Health 63: 53–58CrossRefGoogle Scholar
  104. 104.
    Wells CE (1959) Cerebral embolism: The natural history, prognostic signs, and effects of anticoagulation. AMA Arch Neurol Psychiatr 81: 667–677Google Scholar
  105. 105.
    Howell DA, Tatlow TWF, Feldman S (1964) Observations on anticoagulant therapy in thromboembolic disease of the brain. Can Med Assoc J 90: 611–614PubMedGoogle Scholar
  106. 106.
    Carter AB (1965) Prognosis of cerebral embolism. Lancet ii: 514–519Google Scholar
  107. 107.
    De Wit H, Wise RA (1977) Blockade of cocaine reinforcement in rats with the dopamine receptor blocker pimozide, but not with the noradrenergic blockers phentolamine and phenoxybenz- amine. Can J Psychol 31: 195–203PubMedCrossRefGoogle Scholar
  108. 108.
    Baker RN, Broward JA, Fang HC, Fisher CM, Groch SN, Heyman A, Karp HR, McDevitt E, Scheinberg P, Schwartz W, Toole JF (1962) Anaticoagulant therapy in cerebral infarction. Neurology 12: 823–835PubMedGoogle Scholar
  109. 109.
    Fisher CM, Adams RD (1951) Observations on brain embolism with special reference to the mechanism of hemorrhagic infarction. J Neuropathol Exp Neurol 10: 92–94PubMedGoogle Scholar
  110. 110.
    Jorgensen L, Torvik A (1969) Ischaemic cerebrovascular diseases in an autopsy series. Part 2. Prevalence, location, pathogenesis, and clinical course of cerebral infarcts. J Neurol Sci 9: 285–320Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • G. J. Del Zoppo
    • 1
  1. 1.Department of Basic and Clinical ResearchScripps Clinic and Research FoundationLa JollaUSA

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