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Research of prevention and mechanisms for coronary reocclusion after coronary thrombolytic therapy

Research Project

Project/Area Number 05670621
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionKumamoto University

Principal Investigator

OGAWA Hisao  Division of Cardiology, Kumamoto University School of Medicine Lecturer, 医学部・付属病院, 講師 (50177135)

Co-Investigator(Kenkyū-buntansha) YASUE Hirofumi  Division of Cardiology, Kumamoto University School of Medicine Professor, 医学部, 教授 (40174502)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsAcute Myocardial Infarction / Coronary Thrombolytic Therapy / Reocclusion / Tissue-type plasminogen activator / Plasminogen activator inhibitor / Activated protein C / tissue-type plasminogen activator / activated protein C / t-PA / thrombolysis / reocclusion
Research Abstract

Reocclusion of recanalized coronary arteries often limits the efficacy of coronary thrombolytic therapy in patients with acute myocardial infarction. The fibrinolytic system is impaired in patients with acute myocardial infarction. The primary regulatory element of fibrinolytic activity is plasminogen activator inhibitor (PAI). We measured the serial changes of PAI activity and tissue plasminogen activator (t-PA) antigen after recombinant t-PA (rt-PA) therapy. Plasma PAI activity levels were increased on admission and further increased within 24 hours in patients treated with rt-PA.There were two peaks in plasma PAI activity levels (IU/ml) at 4 hours (27.0<plus-minus>2.9) and at 16 hours (25.6<plus-minus>2.5) after the initiation of rt-PA infusion. The early increase of PAI activity may diminish the efficiency of reperfusion of rt
Activated protein C (APC) is an important regulatory enzyme in hemostasis. After activation by thrombin-thrombomodulin complex on the endothelial cells, APC i … More nactivated factors VIIIa and Va and leads to inhibition of thrombin formation. APC also has been shown to enhance clot lysis by inhibiting the activity of PAI in endothelial cell cultures and in clot lysis assays. In view of the potential of human APC as an anticoagulant and profibrinolytic agent, the effect of APC on thrombolysis with rt-PA was studied in a canine model of coronary artery thrombosis. The dogs were randomly assigned to receive one of the following intravenous adjunctive hterapies : (1) control group ; (2) APC group : APC (0.6mg/kg) at a rate of 0.83mL/min ; (3) heparin group : heparin (200U/kg) at a rate of 0.83mL/min. In a 120-min observation after the termination of rt-PA,reocclusion developed in all the dogs in the control and heparin groups but in only 3 of the 10 dogs in the APC group. Time from recanalization to reocclusion was prolonged in the APC group as compared with the control and heparin groups. Bleeding time was prolonged in only the heparin group after the treatment. It is concluded that APC prevents coronary artery reocclusion after recanalization with rt-PA in a canine model of coronary artery thrombosis. Less

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Tomohiro Sakamoto, Hisao Ogawa, et al: "Prevention of arterial reocclusion after thrombolysis with activated protein C." Circulation. 90. 427-432 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takenobu Masuda, Hisao Ogawa, et al.: "Circadian variation in fibrinolytic activity in patients with variant angina" British Heart Journal. 71. 156-161 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yuji Miyao, Hirofumi Yase, Hisao Ogawa, et al.: "Elevated plasma interleukin-6 levels in patients with acute myocardial infarction" American Heart Journal. 126. 1299-1304 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hisao Ogawa, et al.: "Difference in plasminogen activator inhibitor activity between non-Q-wave infarction and Q-wave infarction" Intemational Journal of Cardiology. 41. 201-208 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hisao Ogawa, et al.: "Platelet-derived growth factor is released into the coronary circulation after coronary spasm." Coronary Artery Disease. 4. 437-442 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ikuo Misumi, Hisao Ogawa, et al.: "Increased plasma plasminogen activator inhibitor activity after coronary spasm." International Journal of Cardiology. 41. 21-29 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tomohiro Sakamoto, Hisao Ogawa, Hirofumi Yasue, Yoshiaki Oda, Shuuji Kitajima, Kenji Tsumoto, Hiroshi Mizokami: "Prevention of arterial reocclusion after thrombolysis with activated protein C.Comparison with Heparin in a canine model of coronary artery thrombosis." Circulation. 90. 427-432 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshio Honda, Shuichi Oshima, Hisao Ogawa, Tomohiro Sakamoto, Yuji Miyao, shinji Sakata, Osamu Hirashima, Yasushi Morikami, Hirofumi Yasue: "Plasma lipoprotein (a) levels and fibrinolytic activity in acute myocardial infarction." Japanese Circulation Journal. 58. 869-876 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takenobu Masuda, Hisao Ogawa, Yuji Miyao, Quanjun Yu, Ikuo Misumi, Tomohiro Sakamoto, Hiroto Okubo, Ken Okumura, Hirofumi Yasue.: "Circadian variation in fibrinolytic activity in patients with variant angina." British Heart Journal. 71. 156-161 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yuji Miyao, Hirofumi Yasue, Hisao Ogawa, Ikuo Misumi, Takenobu Masuda, Tomohiro Sakamoto, Etsuo Morita.: "Elevated plasma interleukin-6 levels in patients with acute myocardial infarction." American Heart Journal. 126. 1299-1304 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hisao Ogawa, Ikuo Misumi, Tomohiro Sakamoto, Takenobu Masuda, Hiroto Okubo, Yuji Miyao, Hirofumi Yasue.: "Difference in plasminogen activator inhibitor activity between non-Q-wave infarction and Q-wave infarction." International Journal of Cardiology. 41. 201-208 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hisao Ogawa, Hirofumi Yasue, Ken Okumura, Hiromi Fujii, Takenobu Masuda, Yuji Miyao, Satoko Bannai, Naoki Takanashi: "Platelet-derived growth factor is released into the coronary circulation after coronary spasm." Coronary Artery Disease. 4. 437-332 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ikuo Misumi, Hisao Ogawa, Takenobu Masuda, Tomohiro Sakamoto, Ken Okumura, Hirofumi Yasue.: "Increased plasma plasminogen activator inhibitor activity after coronary spasm." International Journal of Cardiology. 41. 21-29 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tomohiro Sakamoto,Hisao Ogawa,et al.: "Prevention of arterial reocclusion after thrombolysis with activated protein C" Circulation. 90. 427-432 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takenobu Masuda,Hisao Ogawa,et al.: "Circadian variation in fibrinolytic activity in patients with variant angina" British Heart Journal. 71. 156-161 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yuji Miyao,Hirofumi Yasue,Hisao Ogawa,et al: "Elevated plasma interleukin-6 levels in patients with acute myocardial infarction" American Heart Journal. 126. 1299-1304 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hisao Ogawa,et al.: "Difference in plasminogen activator inhibitor activity between non-Q-wave infarction and Q-wave infarction" International Journal of Cardiology. 41. 201-208 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hisao Ogawa,et al.: "Platelet-derived growth factor is released into the coronary circulation after coronary spasm." Coronary Artery Disease. 4. 437-442 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ikuo Misumi,Hisao Ogawa,et al.: "Increased plasma plasminogen activator inhibitor activity after coronary spasm." International Journal of Cardiology. 41. 21-29 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ikuo Misumi: "Increased plasma plasminogen activator inhibitor activity after coronary spasm" International Journal of Cardiology. 41. 21-29 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hisao Ogawa: "Difference in plasminogen activator inhibitor activity between non-O-wave infarction and O-wave infarction" International Journal of Cardiology. 41. 201-208 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kiyotaka Kugiyama: "Transferable lipids in oxidized low-density lipoprotein stimulate PAI-1 and inhibit t-PA release from endothelial cells" Circulation Research. 73. 335-343 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yuji Miyao: "Eleveted plasma interleukin-6 levels in patients with acute myocardial infarction" American Heart Journal. 126. 1299-1304 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takenobu Masuda: "Circadian variation in fibrinolytic activity in patients with variant angina" British Heart Journal. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tomohiro Sakamoto: "Prevention of arterial reocclusion after thrombolysis with activated protein C" Circulation. (in press). (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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