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Thromb Haemost 1998; 79(03): 663-667
DOI: 10.1055/s-0037-1614963
Review Articles
Schattauer GmbH

Enhancement of Tissue-type Plasminogen Activator-induced Thrombolysis and Prevention of Reocclusion by Combination with a Humanized Anti-glycoprotein IIb/IIIa Monoclonal Antibody, YM337, in a Rhesus Monkey Model of Coronary Thrombosis

Tomihisa Kawasaki
1   Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Kazuo Sato
1   Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Ken-ichi Suzuki
1   Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Yumiko Sakai
1   Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Yuta Taniuchi
1   Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Seiji Kaku
1   Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Shinya Yano
1   Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Osamu Inagaki
1   Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Kenichi Tomioka
1   Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Yasuhiko Masuho
1   Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Isao Yanagisawa
1   Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
,
Toichi Takenaka
1   Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan
› Author Affiliations
Further Information

Publication History

Received 30 January 1998

Accepted after resubmission 05 November 1998

Publication Date:
07 December 2017 (online)

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Summary

We examined the effect of a humanized anti-glycoprotein IIb/IIIa monoclonal antibody, YM337, on thrombolysis with tissue-type plasminogen activator in a copper coil-induced coronary thrombosis model in rhesus monkeys. Fifty minutes after the formation of an occlusive thrombus, a test drug was administered by either i.v. bolus injection followed by continuous infusion (YM337, 0.25 mg/kg + 1.5 μg/kg/min) or i.v. bolus injection (aspirin, 17 mg/kg). Sixty minutes after induction of the occlusive thrombus, thrombolysis was initiated with tPA at a total dose of 0.5 mg/kg intravenously administered over 60 min, with 10% given as an initial bolus. The median time to reperfusion was significantly shortened by YM337 [saline, 60 min (n = 5); aspirin, 45 min (n = 5); YM337, 30 min (n = 5)]. The incidence of reocclusion was significantly decreased by YM337 (saline, 4/4; aspirin, 5/5; YM337, 1/5), and the median time to reocclusion was significantly prolonged by YM337 [saline, 30 min (n = 4); aspirin, 30 min (n = 5); YM337, 180 min (n = 5)]. YM337 significantly reduced the thrombus protein content at the end of experiment. ADP-induced platelet aggregation was completely inhibited by YM337. These results suggest that YM337 may be of clinical value as an adjunctive agent in thrombolytic therapy for patients with acute myocardial infarction.

 

  • References

  • 1 Plow EF, Ginsberg MH. Cellular adhesion: GPIIb/IIIa as a prototypic adhesion receptor.. Prog Hemost Thromb 1989; 9: 117-56.
    PubMedSearch in Google Scholar
  • 2 Phillips DR, Charo IF, Parise LV, Fitzgerald LA. The platelet membrane glycoprotein IIb/IIIa complex.. Blood 1988; 71: 831-43.
    PubMedSearch in Google Scholar
  • 3 The EPIC Investigators.. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty.. N Engl J Med 1994; 330: 956-61.
    CrossrefPubMedSearch in Google Scholar
  • 4 Topol EJ, Califf RM, Weisman HF, Ellis SG, Tcheng JE, Worley S, Ivanhoe R, George BS, Fintel D, Weston M, Sigmon K, Anderson KM, Lee KL, Willerson JT. on behalf of the EPIC Investigators. Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months.. Lancet 1994; 343: 881-6.
    CrossrefPubMedSearch in Google Scholar
  • 5 Aguirre FV, Topol EJ, Ferguson JJ, Anderson K, Blankenship JC, Heuser RR, Sigmon K, Taylor M, Gottlieb R, Hanovich G, Rosenberg M, Donohue TJ, Weisman HF, Califf RM. for the EPIC Investigators. Bleeding complications with the chimeric antibody to platelet glycoprotein IIb/IIIa integrin in patients undergoing percutaneous coronary intervention.. Circulation 1995; 91: 2882-90.
    CrossrefPubMedSearch in Google Scholar
  • 6 Bernardi MM, Califf RM, Kleiman N, Ellis SG, Topol EJ. for the TAMI Study Group. Lack of usefulness of prolonged bleeding times in predicting hemorrhagic events in patients receiving the 7E3 glycoprotein IIb/IIIa platelet antibody.. Am J Cardiol 1993; 72: 1121-5.
    CrossrefPubMedSearch in Google Scholar
  • 7 Topol EJ, Plow EF. Clinical trials of platelet receptor inhibitors.. Thromb Haemost 1993; 70: 94-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Bruggemann M, Winter G, Waldmann H, Neuberger MS. The immunogenicity of chimeric antibodies.. J Exp Med 1989; 170: 2153-7.
    CrossrefPubMedSearch in Google Scholar
  • 9 Co MS, Yano S, Hsu RK, Landolfi NF, Vasquez M, Cole M, Tso JT, Bringman T, Laird W, Hudson D, Kawamura K, Suzuki K, Furuichi K, Queen C, Masuho Y. A humanized antibody specific for platelet integrin gpIIb/IIIa.. J Immunol 1994; 152: 2968-76.
    PubMedSearch in Google Scholar
  • 10 Yano S, Suzuki K, Katoh M, Sugita Y, Kaku S, Kawamura K, Masuho Y. Epitopes and biological activities of two monoclonal antibodies to platelet integrin αIIbβIII.. J Biochem 1994; 116: 778-86.
    CrossrefPubMedSearch in Google Scholar
  • 11 Kaku S, Kawasaki T, Sakai Y, Taniuchi Y, Yano S, Suzuki K, Terazaki C, Kawamura K, Masuho Y, Satoh N, Takenaka T, Yanagi K, Ohshima N. Antithrombotic effect of a humanized anti-GPIIb/IIIa monoclonal antibody, YM207, in a photochemically induced thrombosis model in monkeys.. Eur J Pharmacol 1995; 279: 115-21.
    CrossrefPubMedSearch in Google Scholar
  • 12 Yano S, Suzuki K, Sato K, Terazaki C, Hisamichi N, Kaku S, Sakai Y, Taniuchi Y, Kawasaki T, Inagaki O, Sugita Y, Satoh N, Takenaka T, Masuho Y. Antiplatelet agent YM337 inhibits platelet function with little effect on bleeding time in monkeys.. Blood 1995; 86 (Suppl. 01) 912a (abstract #3636).
    PubMedSearch in Google Scholar
  • 13 Suzuki K, Sakai Y, Hisamichi N, Taniuchi Y, Satoh K, Terazaki C, Kaku S, Kawasaki T, Yano S, Inagaki O, Masuho Y. Comparison of antiplatelet effect of YM337 and abciximab in rhesus monkeys.. Eur J Pharmacol 1998; 336: 169-76.
    PubMedSearch in Google Scholar
  • 14 Kaku S, Kawasaki T, Hisamichi N, Sakai Y, Taniuchi Y, Inagaki O, Yano S, Suzuki K, Terazaki C, Masuho Y, Satoh N, Takenaka T, Yanagi K, Ohshima N. Antiplatelet and antithrombotic effects of YM337, the Fab fragment of a humanized anti-GPIIb/IIIa monoclonal antibody in monkeys.. Thromb Haemost 1996; 75: 679-84.
    Thieme ConnectPubMedSearch in Google Scholar
  • 15 Harlow E, Lane D. Antibodies: a laboratory manual.. Cold Spring Harbor Laboratory Press; New York: 1988: 630-1.
    Search in Google Scholar
  • 16 Susawa T, Yui Y, Hattori R, Takahashi M, Aoyama T, Takatsu Y, Sakaguchi K, Yui N, Kawai C. Heparin requirement in tissue-type plasminogen activator-induced experimental coronary thrombolysis: comparison with urokinase-induced coronary thrombolysis.. Jpn Circ J 1987; 51: 431-5.
    CrossrefPubMedSearch in Google Scholar
  • 17 Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, Dodge HT, Francis CK, Hillis D, Ludbrook P, Markis JE, Mueller H, Passamani ER, Powers ER, Rao AK, Robertson T, Ross A, Ryan TJ, Sobel BE, Willerson J, Williams DO, Zaret BL, Braunwald E. Thrombolysis in myocardial infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge.. Circulation 1987; 76: 142-54.
    CrossrefPubMedSearch in Google Scholar
  • 18 Tiefenbrunn AJ, Robinson AK, Kurnik PB, Ludbrook PA, Sobel BE. Clinical pharmacology in patients with evolving myocardial infarction of tissue-type plasminogen activator produced by recombinant DNA technology.. Circulation 1985; 71: 110-6.
    CrossrefPubMedSearch in Google Scholar
  • 19 Ratnoff OD, Menzie C. A new method for the determination of fibrinogen in small samples of plasma.. J Lab Clin Med 1951; 37: 316-20.
    PubMedSearch in Google Scholar
  • 20 Lu HR, Gold HK, Wu Z, Cock FD, Jang IK, Pauwels P, Collen D. Acceleration and persistence of recombinant tissue plasminogen activator-induced arterial eversion graft recanalization with a single bolus injection of F(ab’)2 fragments of the antiplatelet glycoprotein IIb/IIIa antibody 7E3.. Coron Art Dis 1991; 2: 1039-46.
    PubMedSearch in Google Scholar
  • 21 Holahan MA, Mellott MJ, Garsky VM, Shebuski RJ. Prevention of reocclusion following tissue type plasminogen activator-induced thrombolysis by the RGD-containing peptide, echistatin, in a canine model of coronary thrombosis.. Pharmacology 1991; 42: 340-8.
    CrossrefPubMedSearch in Google Scholar
  • 22 Yasuda T, Gold HK, Kohmura C, Guerrero L, Yaoita H, Fallon JT, Bunting S, Collen D. Intravenous and endobronchial administration of G4120, a cyclic Arg-GlyAsp-containing platelet GPIIb/IIIa receptor-blocking pentapeptide, enhances and sustains coronary arterial thrombolysis with rt-PA in a canine preparation.. Arterioscler Thromb 1993; 13: 738-47.
    CrossrefPubMedSearch in Google Scholar
  • 23 Lucchessi BR, Rote WE, Driscoll EM, Mu D-X. Prevention of thrombosis and rethrombosis and enhancement of the thrombolytic actions of recombinant tissue-type plasminogen activator in the canine heart by DMP728, a glycoprotein IIb/IIIa antagonist.. Br J Pharmacol 1994; 113: 1333-43.
    CrossrefPubMedSearch in Google Scholar
  • 24 Roux SP, Tschopp TB, Kuhn H, Steiner B, Hadvary P. Effects of heparin, aspirin and a synthetic platelet glycoprotein IIb/IIIa receptor antagonist (Ro43-5054) on coronary artery reperfusion and reocclusion after thrombolysis with tissue-type plasminogen activator in the dog.. J Pharmacol Exp Ther 1993; 264: 501-8.
    PubMedSearch in Google Scholar
  • 25 ISIS-2 Collaborative Group.. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2.. Lancet 1988; 2: 349-60.
    PubMedSearch in Google Scholar
  • 26 Kohmura C, Gold HK, Yasuda T, Holt R, Nedelman MA, Guerrero JL, Weisman HF, Collen D. A chimeric murine/human antibody Fab fragment directed against the platelet GPIIb/IIIa receptor enhances and sustains arterial thrombolysis with recombinant tissue-type plasminogen activator in baboons.. Arterioscler Thromb 1993; 13: 1837-42.
    CrossrefPubMedSearch in Google Scholar
  • 27 Yasuda T, Gold HK, Yaoita H, Leinvbach RC, Guerrero JL, Jang IK, Holt R, Fallon JT, Collen D. Comparative effects of aspirin, a synthetic thrombin inhibitor and a monoclonal antiplatelet glycoprotein IIb/IIIa antibody on coronary artery reperfusion, reocclusion and bleeding with recombinant tissue-type plasminogen activator in a canine preparation.. J Am Coll Cardiol 1990; 16: 714-22.
    CrossrefPubMedSearch in Google Scholar
  • 28 Badimon L, Lassila R, Badimon J, Vallabhajosula S, Chesebro JH, Fuster V. Residual thrombus is more thrombogenic than severely damaged vessel wall.. Circulation 1988; 78 (suppl. II) II-119 (abstract).
    PubMedSearch in Google Scholar
  • 29 Bush LR, Shebuski RJ. In vivo models of arterial thrombosis and thrombo-lysis.. FASEB J. 1990; 4: 3087-98.
    CrossrefPubMedSearch in Google Scholar
  • 30 Schror K. Antiplatelet drugs.. Drugs 1995; 50: 7-28.
    CrossrefPubMedSearch in Google Scholar
  • 31 Cook NS, Kottirsch G, Zerwes H-G. Platelet glycoprotein IIb/IIIa antagonists.. Drugs of the Future 1994; 19: 135-59.
    PubMedSearch in Google Scholar
  • 32 Coller BS, Scudder LE, Beer J, Gold HK, Folts JD, Cavagnaro J, Jordan R, Wagner C, Iuliucci J, Knight D, Ghrayeb J, Smith C, Weisman HF, Berger H. Monoclonal antibodies to platelet glycoprotein IIb/IIIa as antithrombotic agents.. Ann NY Acad Sci 1991; 614: 193-213.
    CrossrefPubMedSearch in Google Scholar
  • 33 Kleiman NS, Ohman EM, Califf RM, George BS, Kereiakes D, Aguirre FV, Weisman H, Schaible T, Topol EJ. Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab after thrombolytic therapy. Results of the Thrombo-lysis and Angioplasty in Myocardial Infarction (TAMI) 8 Pilot Study.. J Am Coll Cardiol 1993; 22: 381-9.
    CrossrefPubMedSearch in Google Scholar