Protective Effects of a Thromboxane Synthetase Inhibitor, a Thromboxane Antagonist, a Lipoxygenase Inhibitor and a Leukotriene C_4, D_4 Antagonist on Myocardial Injury Caused by Acute Myocardial Infarction in the Canine Heart : SYMPOSIUM ON PROTECTION OF
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概要
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We studied the effects of a thromboxane A_2 synthetase inhibitor (RS-5186), a thromboxane A_2 antagonist (ONO-3708), a 5-lipoxygenase inhibitor (AA-861) and a peptidoleukotriene antagonist (ONO-1078) on infarct size, polymorphonuclear leukocyte infiltration, gross myocardial hemorrhage and arrhythmias in the canine coronary occlusion (2 hour)-reperfusion model (5 hour). The infarct size and risk area were determined by a double staining technique. Thirty minutes prior to occluding the coronary arteries, dogs were randomly assigned to one of the following five groups: the thromboxane A_2 synthetase inhibitor group (n=11) receiving RS-5186 10 mg/kg i.v., the thromboxane A_2 antagonist group(n=12) receiving continuous intravenous infusion of ONO-3708 1 μg/kg/min, the lipoxygenase inhibitor group (n=11) receiving AA-861 3 mg/kg i.v., the peptidoleukotriene antagonist group (n=11) receiving continuous intravenous infusion of ONO-1078 1μg/kg/min and the vehicle control group (n=15). Except for ONO-3708, all the other drugs reduced the infarct size (RS-5186: 26.3±2.4% of risk area (mean±SEM), AA-861: 21.8±1.3%, ONO-1078: 22.5±4.4% vs control: 54.0±6.4%, p<0.01 respectively) as well as reducing the area of gross myocardial hemorrhage (RS-5186: 3.9±2.6% of infarct size, AA-861: 5.1±2.4%, ONO-1078: 5.2±2.5% vs control: 22.3±3.9%, p<0.01 respectively). RS-5186 and AA-861 reduced the intensity of polymorphonuclear leukocyte infiltration into the infarcted area, however, neither ONO-3708 nor ONO-1078 had any significant influence. These results suggested that eicosanoid products, especially thromboxane A_2 and leukotriene C_4, D_4 play important roles in the pathogenesis of myocardial ischemic and reperfusion injuries and that the new thromboxane A_2 synthetase inhibitor RS-5186, the lipoxygenase inhibitor AA-861, and the peptidoleukotriene antagonist ONO-1078 might be useful in salvaging ischemic myocardium.
- 社団法人日本循環器学会の論文
- 1989-09-20
著者
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Ito Takayuki
Department Of Health Sciences Nagoya University School Of Medicine
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Ogawa Kouichi
2nd Department Of Internal Medicine Nagoya University School Of Medicine
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ITO TAKAYUKI
2nd Department of Internal Medicine, Nagoya University School of Medicine
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TOKI YUKIO
2nd Department of Internal Medicine, Nagoya University School of Medicine
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HIEDA NOBUYUKI
2nd Department of Internal Medicine, Nagoya University School of Medicine
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OKUMURA KENJI
2nd Department of Internal Medicine, Nagoya University School of Medicine
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HASHIMOTO HIDEKAZU
2nd Department of Internal Medicine, Nagoya University School of Medicine
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SATAKE TATSUO
2nd Department of Internal Medicine, Nagoya University School of Medicine
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Ogawa Kouichi
Meijo Hospital
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Satake T
Departments Of Internal Medicine Faculty Of Medicine University Of Nagoya
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Hieda Nobuyuki
2nd Department Of Internal Medicine Nagoya University School Of Medicine
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TOKI Yukio
Department of Internal Medicine II, Nagoya University School of Medicine
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Toki Yukio
Internal Medicine Ii Nagoya University School Of Medicine
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Ogawa K
Meijo Hospital
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Shibata T
Nagoya Univ. Nagoya Jpn
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Ogawa Kouichi
Second Department Of Internal Medicine Nagoy University School Of Medicine
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Satake Tatsuo
Faculty Of Medicine University Of Nagoya
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Hashimoto Hidekazu
Internal Medicine Ii Nagoya University School Of Medicine
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Hashimoto Hidekazu
2nd Department Of Internal Medicine Nagoya University School Of Medicine
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Satake Tatsuo
2nd Department Of Internal Medicine Nagoya University School Of Medicine Nagoya.
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Satake Tatsuo
The 2nd Dept. Of Internal Medicine Nagoya University School Of Medicine
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Ogawa Kouichi
Department Of Cardiology Meijo Hospital
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Hashimoto H
名古屋大学 第2内科
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Ogawa K
名古屋大学 第2内科
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Ito Takayuki
Departments Of Internal Medicine
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Shibata Tetsuo
名古屋大学 第2内科
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Ogawa Kouichi
The 2nd Dept. Of Internal Medicine Nagoya University School Of Medicine
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Hieda Nobuyuki
Departement Of Biomedical Chemistry Faculty Of Medicine University Of Nagoya
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Okumura Kenji
2nd Department Of Internal Medicine Nagoya University School Of Medicine Nagoya.
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