Combination of N-Methyl-1-Deoxynojirimycin and Ischemic Preconditioning Markedly Reduces the Size of Myocardial Infarcts in Rabbits
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概要
- 論文の詳細を見る
N-methyl-1-deoxynojirimycin (NMDN), an α-glucosidase inhibitor, reduces myocardial infarct size by reducing the glycogenolytic rate through inhibition of the α-1, 6-glucosidase of glycogen-debranching enzyme in the heart, in addition to possessing an antihyperglycemic action by blocking α-1, 4-glucosidase in the intestine. Ischemic preconditioning (PC), which markedly reduces the size of the myocardial infarct, is known to reduce the activity of phosphorylase and reduce the glycogenolytic rate. Therefore, it was hypothesized that a combination of pharmacological inhibition of glycogenolysis by an α-1, 6-glucosidase inhibitor, NMDN, and PC could markedly reduce myocardial inharct size more than NMDN or PC alone. Japanese white rabbits without collateral circulation were subjected to a 30-min coronary occlusion followed by 48-h reperfusion. The infarct sizes as a percentage of area at risk were significantly reduced by pre-ischemic treatment with either 100 mg/kg of NMDN or PC of 5 min ischemia and 5 min reperfusion alone (15.9±2.0%, n=8, and 10.3±1.2%, n=8, respectively) as compared with the control (43.9±2.2%, n=8). However, the combination of 100 mg/kg of NMDN and PC significantly reduced the infarct size (4.9±1.2, n=8) compared with NMDN or PC alone. Another 40 rabbits, also given 100 mg of NMDN, PC, NMDN+PC or saline before ischemia (n=10 in each group), were killed for biochemical analysis after 30 min of ischemia. NMDN and PC preserved the glycogen content and attenuated the lactate accumulation, respectively, as compared with the control. However, the combination of NMDN and PC preserved significantly more glycogen and significantly reduced lactate accumulation than either NMDN or PC alone. The combination of NMDN and PC markedly reduced the myocardial infarct size more than either process alone. The marked preservation of glycogen and marked attenuation of lactate accumulation by the combination of NMDN and PC suggest that the mechanism for this effect of NMDN+PC is related to the inhibition of glycogenolysis.
- 社団法人日本循環器学会の論文
- 2001-06-20
著者
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MINATOGUCHI Shinya
Second Department of Internal Medicine, Gifu University Graduate School of Medicine
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TAKEMURA Genzou
Second Department of Internal Medicine, Gifu University Graduate School of Medicine
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FUJIWARA Hisayoshi
Second Department of Internal Medicine, Gifu University School of Medicine
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Fujiwara Takako
Kyoto Women's University
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Arai Masazumi
Second Department of Internal Medicine, Gifu University School of Medicine
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Uno Yoshihiro
Department Of Cardiology Gifu University Graduate School Of Medicine
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WANG Ningyuan
Second Department of Internal Medicine, Gifu University School of Medicine
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Wu Der-jinn
Chung Shang Medical University Hospital
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Wang Ningyuan
Second Department Of Internal Medicine Gifu University School Of Medicine
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Uno Yoshihiro
Second Department of Internal Medicine, Gifu University School of Medicine
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Nishida Yoshio
Second Department of Internal Medicine, Gifu University School of Medicine
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Hashimoto Kazuaki
Second Department of Internal Medicine, Gifu University School of Medicine
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Uno Yoshihiro
The 2^<nd> Department Of Internal Medicine Gifu University School Of Medicine
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Fujiwara Takako
Kyoto Women's University
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Hashimoto Kazuaki
2nd Department of internal Medicine, Gifu University School of Medicine
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Wu Der-Jinn
Department of Internal Medicine, Chung-Shan Medical and Dental College Hospital
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Hashimoto Yasuko
Second Department of Internal Medicine, Gifu University School of Medicine
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Fujiwara Hisayoshi
Second Department Of Internal Medicine Gifu University Graduate School Of Medicine
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Minatoguchi Shinya
Second Department Of Internal Medicine Gifu University Graduate School Of Medicine
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Wu Der-jinn
The Third Division Departments Of Internal Medicine
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Nishida Yoshio
Second Department Of Internal Medicine Gifu University School Of Medicine
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Hashimoto Kazuaki
2nd Department Of Internal Medicine Gifu University School Of Medicine
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Hashimoto Yasuko
Second Department Of Internal Medicine Gifu University School Of Medicine
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Fujiwara Hisayoshi
Second Department Of Internal Medicine Faeulty Of Medicine Gifu University
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Takemura Genzou
Second Dep. Of Internal Medicine Graduate School Of Medicine Gifu Univ.
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WU Der-Jinn
Department of Internal Medicine, Chung Shan Medical and Dental College Hospital
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