title: Acarbose reduces myocardial infarct size by preventing postprandial hyperglycemia and hydroxyl radical production and opening mitochondrial KATP channels in rabbits.
abstract: BACKGROUND
  Acarbose, an antidiabetic drug, is an alpha-glucosidase inhibitor that can inhibit glucose absorption in the intestine. A recent large-scale clinical trial, STOP-NIDDM, showed that acarbose reduces the risk of myocardial infarction. We examined whether acarbose reduces myocardial infarct size and investigated its mechanisms.
  
  
  RESULTS
  Rabbits were fed with 1 of 2 diets in this study: normal chow, 30 mg acarbose per 100 g chow for 7 days. Rabbits were assigned randomly to 1 of 4 groups: control (n = 10), acarbose (n = 10), acarbose + 5HD (n = 10, intravenous 5 mg/kg of 5-hydroxydecanoate), and 5HD (n = 10, intravenous 5 mg/kg of 5HD). Rabbits then underwent 30 minutes of coronary occlusion followed by 48-hour reperfusion. Postprandial blood glucose levels were higher in the control group than in the acarbose group. The infarct size as a percentage of the left ventricular area at risk was reduced significantly in the acarbose (19.4% +/- 2.3%) compared with the control groups (42.8% +/- 5.4%). The infarct size-reducing effect of acarbose was abolished by 5HD (43.4% +/- 4.7%). Myocardial interstitial 2,5-dihydroxybenzoic acid levels, an indicator of hydroxyl radicals, increased during reperfusion after 30 minutes of ischemia, but this increase was inhibited in the acarbose group. This was reversed by 5HD.
  
  
  CONCLUSIONS
  Acarbose reduces myocardial infarct size by opening mitochondrial KATP channels, which may be related to the prevention of postprandial hyperglycemia and hydroxyl radical production.
authors.affiliation: Second Department of Internal Medicine, Gifu University School of Medicine, Gifu 501-1194, Gifu 500, Japan. minatos@gifu-u.ac.jp
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: Zengi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Narentuoya
authors.initials: N
authors.lastname: Bao
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Yasuda
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Iwasa
authors.forename: Syouhei
authors.initials: S
authors.lastname: Sumi
authors.forename: Itta
authors.initials: I
authors.lastname: Kawamura
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishigaki
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D020909:Acarbose / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002396:Catechols / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005841:Gentisates / Q000378:metabolism; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D006943:Hyperglycemia / Q000188:drug therapy*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D015221:Potassium Channels / Q000378:metabolism*; D011817:Rabbits
chemical_list: D001786:Blood Glucose; D002396:Catechols; D004791:Enzyme Inhibitors; D005841:Gentisates; D062385:Hydroxybenzoates; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; C034221:catechol; D020909:Acarbose; C010925:2,5-dihydroxybenzoic acid