Article date: August 2001
By: Shinya Minatoguchi, Ningyuan Wang, Yoshihiro Uno, Masazumi Arai, Kazuaki Hashimoto, Yasuko Hashimoto, Xue‐Hai Chen, Genzou Takemura, Hisayoshi Fujiwara in Volume 133, Issue 7, pages 1041-1046
The anti‐diabetic drug miglitol, an α‐glucosidase inhibitor, which is currently used clinically, reduces myocardial infarct size by reducing the glycogenolytic rate through inhibition of the α‐1,6‐glucosidase of glycogen‐debranching enzyme in the heart. Nicorandil, a KATP channel opener with a nitrate‐like effect, which is also currently used clinically, also reduces the infarct size. Therefore, we hypothesized that combination of nicorandil and submaximal dose of miglitol could markedly reduce myocardial infarct size more than miglitol or nicorandil alone, and investigated the mechanism for the infarct size‐reducing effect.
Japanese white rabbits without collateral circulation were subjected to 30 min coronary occlusion followed by 48 h reperfusion. Pre‐ischaemic treatment with submaximal dose of miglitol (5 mg kg−1, i.v.) and nicorandil alone (100 μg kg−1 min−1 5 min) moderately reduced the infarct size as a percentage of area at risk (24±4 and 25±4%, respectively), and 10 mg kg−1 of miglitol markedly reduced the infarct size (15±2%) compared with the controls (42±2%). Combination of 5 mg kg−1 of miglitol and nicorandil (100 μg kg−1 min−1 5 min), and 10 mg kg−1 of miglitol and nicorandil (100 μg kg−1 min−1 5 min) significantly reduced the infarct size (13±4 and 12±3%, respectively) more than miglitol or nicorandil alone.
Pretreatment with 5HD completely abolished the infarct size‐reducing effect of 10 mg kg−1 of miglitol alone (36±7%) and that of combination of 5 mg kg−1 of miglitol and nicorandil (46±2%).
Combination of nicorandil and submaximal dose of miglitol markedly reduced the myocardial infarct size more than miglitol or nicorandil alone. This effect was suggested to be related to the opening of mitochondrial KATP channels.
The anti‐diabetic drug miglitol, an α‐glucosidase inhibitor, which is currently used clinically, reduces myocardial infarct size by reducing the glycogenolytic rate through inhibition of the α‐1,6‐glucosidase of glycogen‐debranching enzyme in the heart. Nicorandil, a KATP channel opener with a nitrate‐like effect, which is also currently used clinically, also reduces the infarct size. Therefore, we hypothesized that combination of nicorandil and submaximal dose of miglitol could markedly reduce myocardial infarct size more than miglitol or nicorandil alone, and investigated the mechanism for the infarct size‐reducing effect.
Japanese white rabbits without collateral circulation were subjected to 30 min coronary occlusion followed by 48 h reperfusion. Pre‐ischaemic treatment with submaximal dose of miglitol (5 mg kg−1, i.v.) and nicorandil alone (100 μg kg−1 min−1 5 min) moderately reduced the infarct size as a percentage of area at risk (24±4 and 25±4%, respectively), and 10 mg kg−1 of miglitol markedly reduced the infarct size (15±2%) compared with the controls (42±2%). Combination of 5 mg kg−1 of miglitol and nicorandil (100 μg kg−1 min−1 5 min), and 10 mg kg−1 of miglitol and nicorandil (100 μg kg−1 min−1 5 min) significantly reduced the infarct size (13±4 and 12±3%, respectively) more than miglitol or nicorandil alone.
Pretreatment with 5HD completely abolished the infarct size‐reducing effect of 10 mg kg−1 of miglitol alone (36±7%) and that of combination of 5 mg kg−1 of miglitol and nicorandil (46±2%).
Combination of nicorandil and submaximal dose of miglitol markedly reduced the myocardial infarct size more than miglitol or nicorandil alone. This effect was suggested to be related to the opening of mitochondrial KATP channels.
British Journal of Pharmacology (2001) 133, 1041–1046; doi:10.1038/sj.bjp.0704166
DOI: 10.1038/sj.bjp.0704166
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