1992 Fiscal Year Annual Research Report

冠動脈攣縮の発生機序と臨床的意義に関する研究

Research Project

Project/Area Number	03454257
Research Institution	KUMAMOTO UNIVERSITY HOSPITAL
Principal Investigator	泰江弘文熊本大学, 医学部・附属病院, 教授 (40174502)
Co-Investigator(Kenkyū-buntansha)	松山公三郎熊本大学, 健康管理センター, 助手 (20229587) 藤井裕己熊本大学, 医学部・附属病院, 助手 (40199295) 久木山清貴熊本大学, 医学部・附属病院, 助手 (00225129) 小川久雄熊本大学, 医学部・附属病院, 講師 (50177135) 奥村謙熊本大学, 医学部・附属病院, 助教授 (20185549)
Keywords	冠攣縮 / 狭心症 / 冠攣縮硬化 / アセチルコリン / Mg / フィブリノペプチドA / エンドセリン
Research Abstract	冠動脈の攣縮(冠攣縮)は狭心症や急性心筋梗塞ならびに突然死などの虚血性心疾患の発生上重要な役割を果たしていることが明らかにされつつあり、しかも我が国においては比較的多い疾患である。本研究の第一の目的である冠攣縮と冠動脈硬化との関連については次のことが明らかになった。内皮依存性弛緩物質であるアセチルコリンは、冠動脈が正常な若年者(29歳以下)群では心筋表面を走行する冠動脈を拡張させたが、30歳以上の中高年者群では逆に収縮させた。内皮非依存性弛緩物質であるニトログリセリンはいずれの群においても冠動脈を拡張させた。従って中高年者の大部分では冠動脈の内皮傷害つまり動脈硬化が存在すると考えられた。このことから冠攣縮は冠動脈の内皮傷害、つまり動脈硬化を基盤として発生すると考えられる。一方、冠血流量は若年者群、中高年者群共にアセチルコリンにより増加したので、冠抵抗血管は中高年者においても内皮依存性の弛緩反応が保たれていると考えられた。また、本研究にて冠攣縮の患者の45%に体内Mgの欠乏があることを見出し、Mgと冠攣縮との関連を明らかにした。本研究の第二の目的は冠攣縮と急性心筋梗塞発症の関連については、冠攣縮がトロンビンを活性化させフィブリンを形成し、これが冠動脈血栓、更には急性心筋梗塞にまで至る可能性を血漿フィブリノペプチドAを測定することにより明らかにした。本研究の第三の目的である、強力な血管収縮物質エンドセリンと冠攣縮の関連については、血中エンドセリンは冠攣縮発作前ではなく、発作後に上昇することが明らかとなり、エンドセリンは冠攣縮による心筋虚血の結果、冠静脈洞血中に放出されると結論された。

Research Products
(17 results)

All Other

All Publications (17 results)

[Publications] Takenobu Masuda: "Plasma Plasminogen Activator Inhibitor Activity and Tissue Plasminogen Activator levels in Patients With Unstable Angina and Those With Coronary Spastic Angina." Am Heart J. 124. 314-319 (1992)
[Publications] Hisao Ogawa: "Plasma Platelet-Derived Growth Factor Levels in Coronary Circulation in Unstable Angins Pectoris." Am J Cardiol.69. 453-456 (1992)
[Publications] Tomohiro Sakamoto: "Association of Patency of the Infarct-Related Coronary Artery with Plasma Levels of Plasminogen Activator Inhibitor Activity in Acute Myocardial Infarction." Am J Cardiol. 70. 271-276 (1992)
[Publications] Kozaburo Matsuyama: "Increased Plasma Level of Endothelin-l-Like Immunoreactivity During Coronary Spasm in Patients With Coronary Spastic Angina." Am J Cardiol. 68. 991-995 (1991)
[Publications] Michihisa Jougasaki: "Suppression of Endothelin-1 Secretion by Lysophosphatidylcholine in Oxdized Low Density Lipoprotein in Cultured Vascular Endothelial Cells." Circulation Research. 71. 614-619 (1992)
[Publications] Hiroshi Ishizaka: "Endothelium-Derived Nitric Oxide as a Mediator of Acetylcholine-Induced Coronary Vasodilation in Dogs." J Cardivasc Pharmacol. 18. 665-669 (1991)
[Publications] Hiroshige Yamabe: "Role of Endothelium-Derived Nitric Oxide in Myocardial Reactive Hyperemia." Am J Physiol(Heart Circ. Phiysiol.32). 263. H8-H14 (1992)
[Publications] Toyoaki Murohara: "Age Related Attenuation of the Endothelium-Dependent Relaxation to Noradrenaline in lsolated Pig Coronary Arteries." Cardiovascular Research. 25. 1002-1009 (1991)
[Publications] Kiyotaka Kugiyama: "Lysophosphatidylcholine Inhibits Surface Receptor-Mediated Intracellular Signals in Endothelial Cells by a Pathway Involving Protein Kinase C Activation." Circulation Research. 71. 1422-1428 (1992)
[Publications] Kazuo Goto: "Magnesium Deficiemcy Detected by Intravenous Loading Test in Variant Anglina Pectoris." Am J Cardiol. 65. 709-712 (1990)
[Publications] Shuichi Oshima: "Fibrinopeptide A Is Released Into the Coronary Circulation after Coronary Spasm." Circulation. 82. 2222-2225 (1990)
[Publications] Hirofumi Yasue: "Responses of Angiographically Normal Human Coronary Arteries to Intracronary Injection of Acetylcholine by Age and Segment.Possible Role of Early Coronary Atherosclerosis" Circulation. 81. 482-490 (1990)
[Publications] Ken Okumura: "A study on Coronary Hemodynamics Durig Acetylcholine-Induced Coronary Spasm in Patients With Variant Angina:Endothelium-Dependent Dilation in the Resistance Vessels." J Am Coll Cardiol. 19. 1426-1434 (1990)
[Publications] Ken Okumura: "Effect of Acetylcholine on the Highly Stenotic Coronary Artery : Difference Between the Constrictor Response of the Infarct-Related Coronary Artery and That of the Noninfarct-Related Artery." J Am Coll Cardiol. 19. 752-758 (1992)
[Publications] Kozaburo Matsuyama: "Effects of H1-Receptor Stimulation on Coronary Arterial Diameter and Coronary Hemodynamics in Humans." Circulation. 81. 65-71 (1990)
[Publications] Ken Okumura: "Effects of H1Receptor Stimulation on Coronary Artery Diameter in Patients With Variant Angina:Comparison With Effect of Acetylcholine." J Am Coll Cardiol. 17. 338-345 (1991)
[Publications] Ken Okumura: "Endothelium-Dependent Dilator Response to Substance P in Patients With Coronary Spastic Angina." J Am Coll Cardiol. 20. 838-844 (1992)

1992 Fiscal Year Annual Research Report

冠動脈攣縮の発生機序と臨床的意義に関する研究

Principal Investigator

泰江 弘文 熊本大学, 医学部・附属病院, 教授 (40174502)

Research Products

[Publications] Takenobu Masuda: "Plasma Plasminogen Activator Inhibitor Activity and Tissue Plasminogen Activator levels in Patients With Unstable Angina and Those With Coronary Spastic Angina." Am Heart J. 124. 314-319 (1992)

[Publications] Hisao Ogawa: "Plasma Platelet-Derived Growth Factor Levels in Coronary Circulation in Unstable Angins Pectoris." Am J Cardiol.69. 453-456 (1992)

[Publications] Tomohiro Sakamoto: "Association of Patency of the Infarct-Related Coronary Artery with Plasma Levels of Plasminogen Activator Inhibitor Activity in Acute Myocardial Infarction." Am J Cardiol. 70. 271-276 (1992)

[Publications] Kozaburo Matsuyama: "Increased Plasma Level of Endothelin-l-Like Immunoreactivity During Coronary Spasm in Patients With Coronary Spastic Angina." Am J Cardiol. 68. 991-995 (1991)

[Publications] Michihisa Jougasaki: "Suppression of Endothelin-1 Secretion by Lysophosphatidylcholine in Oxdized Low Density Lipoprotein in Cultured Vascular Endothelial Cells." Circulation Research. 71. 614-619 (1992)

[Publications] Hiroshi Ishizaka: "Endothelium-Derived Nitric Oxide as a Mediator of Acetylcholine-Induced Coronary Vasodilation in Dogs." J Cardivasc Pharmacol. 18. 665-669 (1991)

[Publications] Hiroshige Yamabe: "Role of Endothelium-Derived Nitric Oxide in Myocardial Reactive Hyperemia." Am J Physiol(Heart Circ. Phiysiol.32). 263. H8-H14 (1992)

[Publications] Toyoaki Murohara: "Age Related Attenuation of the Endothelium-Dependent Relaxation to Noradrenaline in lsolated Pig Coronary Arteries." Cardiovascular Research. 25. 1002-1009 (1991)

[Publications] Kiyotaka Kugiyama: "Lysophosphatidylcholine Inhibits Surface Receptor-Mediated Intracellular Signals in Endothelial Cells by a Pathway Involving Protein Kinase C Activation." Circulation Research. 71. 1422-1428 (1992)

[Publications] Kazuo Goto: "Magnesium Deficiemcy Detected by Intravenous Loading Test in Variant Anglina Pectoris." Am J Cardiol. 65. 709-712 (1990)

[Publications] Shuichi Oshima: "Fibrinopeptide A Is Released Into the Coronary Circulation after Coronary Spasm." Circulation. 82. 2222-2225 (1990)

[Publications] Hirofumi Yasue: "Responses of Angiographically Normal Human Coronary Arteries to Intracronary Injection of Acetylcholine by Age and Segment.Possible Role of Early Coronary Atherosclerosis" Circulation. 81. 482-490 (1990)

[Publications] Ken Okumura: "A study on Coronary Hemodynamics Durig Acetylcholine-Induced Coronary Spasm in Patients With Variant Angina:Endothelium-Dependent Dilation in the Resistance Vessels." J Am Coll Cardiol. 19. 1426-1434 (1990)

[Publications] Ken Okumura: "Effect of Acetylcholine on the Highly Stenotic Coronary Artery : Difference Between the Constrictor Response of the Infarct-Related Coronary Artery and That of the Noninfarct-Related Artery." J Am Coll Cardiol. 19. 752-758 (1992)

[Publications] Kozaburo Matsuyama: "Effects of H1-Receptor Stimulation on Coronary Arterial Diameter and Coronary Hemodynamics in Humans." Circulation. 81. 65-71 (1990)

[Publications] Ken Okumura: "Effects of H1Receptor Stimulation on Coronary Artery Diameter in Patients With Variant Angina:Comparison With Effect of Acetylcholine." J Am Coll Cardiol. 17. 338-345 (1991)

[Publications] Ken Okumura: "Endothelium-Dependent Dilator Response to Substance P in Patients With Coronary Spastic Angina." J Am Coll Cardiol. 20. 838-844 (1992)

泰江弘文熊本大学, 医学部・附属病院, 教授 (40174502)