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Development and assessment of animal models appropriate for evaluating thrombolytic agents for an early treatment of acute myocardial infarction

Research Project

Project/Area Number 63870039
Research Category

Grant-in-Aid for Developmental Scientific Research

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionResearch Institute of Angiocardiology and Cardiovascular Clinic Faculty of Medicine, Kyushu University

Principal Investigator

NAKAMURA Motoomi  KYUSHU UNIVERSITY, MEDICINE, PROFESSOR, 医学部, 教授 (60037322)

Co-Investigator(Kenkyū-buntansha) 居石 克夫  九州大学, 医学部, 教授 (70108710)
SUNAGAWA Kenji  KYUSHU UNIVERSITY, MEDICINE, LECTURER, 医学部, 助手 (50163043)
TOMOIKE Hitonobu  KYUSHU UNIVERSITY, MEDICINE, LECTURER, 医学部, 講師 (90112333)
KANAIDE Hideo  KYUSHU UNIVERSITY, MEDICINE, PROFESSOR, 医学部, 教授 (80038851)
TAKESHITA Akira  KYUSHU UNIVERSITY, MEDICINE, ASSO. PROF., 医学部, 助教授 (30038814)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥25,200,000 (Direct Cost: ¥25,200,000)
Fiscal Year 1989: ¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 1988: ¥13,100,000 (Direct Cost: ¥13,100,000)
KeywordsTHROMBOLYSIS / MYOCARDIAL INFARCTION / rt-PA / ANIMAL MODEL / ARTERIOSCLEROSIS / INTRAMURAL HEMORRHAGE / STUNNED MYOCARDIUM / WHHL RABBIT / 急性心筋梗塞発症 / 再潅流障害 / stunned myocardium / 突然死 / 血栓溶解療法 / 遺伝性高脂血症家兎 / 組織プラスミノーゲンアクチベータ / 血栓性閉塞 / 冠動脈硬化
Research Abstract

1. Animal model of myocardial infarction. Animal models with pathophysiological features mimicking to events in acute myocardial infarction in patients with coronary atheroselerosis were developed in Gottingen miniature pigs, WHHL (Watanabe Hereditable Hyperlipidemic) rabbits and dogs.
2. Induction of coronary obstruction due to spasm. Advanced atherosclerotic lesions were produced along the left coronary artery following repeated endothelial denudation by a balloon catheter and X-ray irradiation in Gottingen miniature pigs under diet-induced hypercholesterolemia. Intracoronary injection of serotonin constricted the atherosclerotic vessel near to the level of luminal obstruction. Rapid progression or sustained duration of spasm resulted in intramural hemorrhage around the atheromatous plaque. Acute myocardial infarction was induced in cases with persistent severe spasm.
3. Organic coronary stenosis in WHHL rabbits. Coronary angiography was performed in homozygous WHHL rabbits 10-24 month … More s old to assess the level of coronary stenosis and the responses of the coronary artery to vasoactive agents, including serotonin, histamine, acetylcholine and ergonovine. Severe coronary stenosis was noted at the main trunk of the right and left coronary arteries. Although responses of the coronary arteries in WHHL rabbits to serotonin and ergonovine were larger than that of normal Japanese white rabbits, myocardial infarction was not provoked by these pharmacological interventions.
4. Effects of thrombolytic therapy on infarct size and wall motion. Effects of recombinant tissue-type plasminogen activator (rt-PA) on infarct size and/or left ventricular wall motion following thrombotic occlusion and thrombolytic reperfusion were studied in anesthesized closed chest dogs. Beneficial effects of rt-PA on infarct size depended on the interval after coronary occlusion and was more efficient than the mechanical reperfusion. Thrombolytic but not mechanical reperfusion also improved wall motion which had deteriorated after coronary occlusion. Less

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Hayashi Y.: "Functional and anatomical recovery of endothelium after denudation of coronary artery" Am J Physiol. 254. H1081 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Nagasawa K.: "Intramural hemorrhage and endothelial changes in atherosclerotic coronary artery after repetitive episodes of spasm in X-irradiated hypercolemic pigs." Circ Res. 65. 272-282 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Tomoike H.: "Enhanced responsiveness of smooth muscle,impaired endothelium-dependent relaxation and the genesis of coronary spasm." Am J Cardiol. 63. 33E-39E (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Matsumoto T.: "Characteristics of the histamine-sensitive calcium store in vascular smoth muscle:Comparison with norepinephrineor caffein-sensitive stores." J BIol Chem.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Akaike N.: "Low voltage-activated alcium current in rat aorta smooth muscle cells in primary culture." J Physiol. 416. 141-160 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Satoh S.: "Augmented contraction to histamine of medial smooth muscles at the spastic coronry artery in miniature pigs" Am J Physiol(submitted).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 中村元臣: "最新内科学大系" 中山書店,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Knaide.H: "Recent advances in calciumchannels and calcium antagonists." Parugamon Press,Inc., (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hayashi Y.: "Functional and anatomical recovery of endothelium after denudation of coronary artery." Am J Physiol 254:H1081-H1090, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Nagasawa K.: "Intramural hemorrhage and endothelial changes in atherosclerotic coronary artery after repetitive episodes of spasm in X-irradiated hypercholesterolemic pigs." Circ Res 65: 272-282, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Tomoike H.: "Enhanced responsiveness of smooth muscle, impared endothelium-dependent relaxation and the genesis of coronary spasm." Am J cardiol 63: 33E-39E, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Matsumoto T.: "Characteristics of the histamine-sensitive calcium store in vascular smooth muscle: Comparison with norepinephrine or caffein-sensitive sores." J Biol Chem.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Akaike N.: "Low voltage-activated calcium current in rat aorta smooth muscle cells in primary culture." J Physiol 416: 141-160, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Satoh S.: "Augmented contraction to histamine of medial smooth muscles at the spastic coronary artery i miniature pigs."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kanaide H.: "Recent advances in calciumchannels and calcium antagonists." parugamon press. Inc. (1990).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Nagasaki K.et al: "Intramural hemorrhage and endotheliad changes in atherosclerotic coronry artery after repetitive episodes of spasm in X-irradiated hypercholesterolemic pigs." Circ Res. 65. 272-282 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Tomoike H.et al.: "Homogeneous distribution and pressure dependent reduction of coronary blood flow in right ventricular free wall during coronary hypoperfusion in anesthtized open chest dogs" Cardiovas Res. 23. 31-39 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Adachi H.et al: "Sustained dilation of large coronary artery by α-human atrial natriuretic Peptide in conscious dogs:A comparison with nitroglycerin." Eur J Pharmacol. 161. 189-196 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Satoh S.: "Augmented contraction to histamine of medial smooth muscles at the spastic coronary artery in miniature pigs." Am J Physiol.

    • Related Report
      1989 Annual Research Report
  • [Publications] Tomoike H.: "Enhanced responsiveness of smooth muscle,impared endothelium-dependent relaxation and the genesis of coronary spasm" Am J Cardiol. 63. 33-39 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Matsumoto T.: "Characteristics of the histamine-sensitive calcium store in vascular smooth muscle: Comparison with norepinephrine-or caffein-sensitive stores." J Biol Chem.

    • Related Report
      1989 Annual Research Report
  • [Publications] 中村元臣: "最新内科学大系" 中山書店,

    • Related Report
      1989 Annual Research Report
  • [Publications] Kanaide.H: "Recent advances in calciumchannels and calcium antagonists." Parugamon Press,Inc., (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Nakamura,M.: The FASEB Journal. 2(4). A390 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Mohri,M.: Am Heart J. 117. 43-52 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Tomoike,H.: Cardiovasc Res. 23. 31-39 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Mohri,M.: Circ Res.

    • Related Report
      1988 Annual Research Report
  • [Publications] Nagasawa,K.: Circ Res.

    • Related Report
      1988 Annual Research Report
  • [Publications] Hisano,K.: J Pharmacol.Exp.Ther.

    • Related Report
      1988 Annual Research Report
  • [Publications] Sadoshima,J.: "Voltagedependent anion-selective channels in cultured smooth muscle cells of the rat aorta." Comparative Viochemistry and Physiology, 61-63 (1989)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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