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Pathophysiological Events Related to Coronary Spasm and Provocation of Intramural Hemorrhage at the Spastic Site.

Research Project

Project/Area Number 63440037
Research Category

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

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

Principal Investigator

NAKAMURA Motoomi  Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (60037322)

Co-Investigator(Kenkyū-buntansha) 山元 寅男  九州大学, 医学部, 教授 (80037324)
SUNAGAWA Kenji  Kyushu University, Faculty of Medicine, Lecturer, 医学部, 助手 (50163043)
TOMOIKE Hitonobu  Kyushu University, Faculty of Medicine, Lecturer, 医学部, 講師 (90112333)
KANAIDE Hideo  Kyushu University, Faculty of Medicine, Professor, 医学部, 教授 (80038851)
TAKESHITA Akira  Kyushu University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30038814)
居石 克夫  九州大学, 医学部, 教授 (70108710)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥28,400,000 (Direct Cost: ¥28,400,000)
Fiscal Year 1989: ¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 1988: ¥16,100,000 (Direct Cost: ¥16,100,000)
KeywordsCORONARY ARTERY SPASM / MYOCARDIAL INFARCTION / SEROTONIN / INTRAMURAL HEMORRHAGE / ARTERIOSCLEROSIS / PTCA / ENDOTHELIAL CELL / EDRF / 冠動脈攣縮 / 冠動脈硬化とその進展 / 粥種内出血 / X線照射 / 血管内皮細胞 / 中膜平滑筋
Research Abstract

1. Spontaneous Coronary Constriction Following Mechanical Denudation of the Coronary Artery Mechanisms of spontaneous coronary constriction following balloon injury were studied in situ angiographically. Forty six Gottingen miniature pigs were fed cholesterol rich diet for a month and were randomly allotted to 3 groups; 18 pigs in group I were given 500 units heparin intravenously, 7 in group II both 500 units heparin and 1 mg/kg ketanserin and 21 in group III 3000 units heparin. After these pretreatments, the left anterior descending and/or circumflex coronary arteries were mechanically denuded by a 2F embolectomy catheter. Spontaneous coronary constriction was noted in pigs in group I at the area denuded, which was at its peak level 6 minutes after the injury and was reverted to the control state within 30 minutes. The maximum level of coronary constriction was significantly attenuated from 56<plus-minus>5% in group I to 26<plus-minus>7% and 30<plus-minus>5% in groups II and III, res … More pectively. These results suggest the critical role of the platelet aggregation at the denuded area for the genesis of spontaneous coronary constri
2. Pathogenetic Effects of Coronary Spasm on Progression of Stenosis, Intramural Hemorrhage and/or Acute Myocardial Infarction The role of coronary spasm in the progression of organic coronary stenosis and/or the evolution of acute myocardial infarction was studied in 20 Gottingen miniature pigs fed cholesterol rich diet for 5 months. A branch of the left coronary artery was denuded twice 4 and 5 weeks and were X-irradiated twice 2 and 3 months after the cholesterol feeding. Two months after the 2nd X-irradiation, pigs were randomly allotted to 2 types of provocation of coronary spasm. In 10 pigs in group A, abrupt onset of severe coronary spasm was provoked by 5 intracoronary injections of 10 mug/kg serotonin every 5 minutes. The extent of coronary constriction at the denuded sites was 87<plus-minus>4, 89<plus-minus>5 and 89<plus-minus>5% at 3, 18 and 28 minutes. In group B, stepwise increases of coronary constriction were produced by increasing doses of serotonin from 0.1 to 10 mug/kg serotonin. The extent of coronary constriction was 27<plus-minus>6, 43<plus-minus>5, 57<plus-minus>3, and 85<plus-minus>5 % at 3, 8, 13, and 18 min. The sustained level of coronary constriction was maintained for 25 minutes in 4 of 10 pigs by 5 repetitive injections of 10 mug/kg serotonin (group B1). In other 6 pigs as group B2, sustained constriction was maintained for 120 minutes by 24 repeated injections of 10 mug/kg serotonin. Urokinase was given 600,000units intravenously to pigs in group B2. Intramural hemorrhage was noted at the spastic site in 9 pigs in group A and 3 in group B (p<0.01). Progression of coronary stenosis was confirmed angiographically or histologically in 7 pigs, which was related to the presence of intramural hemorrhage. Acute myocardial infarction was provoked in 5 pigs in group B2, despite the concomitant treatment with a thrombolytic agent. These results suggest that 1) the faster the acceleration of spasm is provoked, the more frequent the occurrence of intramural hemorrhage is noted, 2) intramural hemorrhage augments the extent coronary stenosis and 3) prolonged coronary spasm results in evolution of acute myocardi Less

Report

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

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Hayashi Y.: "Functional and anatomical recovery of endothelium after denudation of coronary artery." Am Jphysiol. 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 hypercoleterolemic 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 norepinephrine or caffein-sensitive stores." J BIol Chem(in press).

    • 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(印刷中)" 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. 1081-1090 (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] Nakamura M.: Saishin Naikagaku taikei. Nakayama shoten,

    • 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] Nagasawa K.et al.: "Intramural hemorrhage and endothelial 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 anesthetized 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 alpha-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. 33E-39E (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] Hayashi Y.: Am J Physiol. 254. H1081-H1090 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Sadoshima J.: Am J Physiol. 255. H410-H418 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Kanaide H.: Circ Res. 63. 15 (1988)

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

    • Related Report
      1988 Annual Research Report
  • [Publications] Tomoike H.: Am J Cardiol.

    • Related Report
      1988 Annual Research Report
  • [Publications] Matumoto T.: J Biol Chem.

    • Related Report
      1988 Annual Research Report
  • [Publications] Sadoshima,J.: "Voltage-dependent anion-selective channels in cultured smooth muscle cells of the rat aorta." Comparative Biochemistry 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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