Acarbose reduces myocardial infarct size by preventing postprandial hyperglycemia and hydroxyl radical production and opening mitochondrial KATP channels in rabbits.
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.
Minatoguchi
Shinya
S
Second Department of Internal Medicine, Gifu University School of Medicine, Gifu 501-1194, Gifu 500, Japan. minatos@gifu-u.ac.jp
Zhang
Zengi
Z
Bao
Narentuoya
N
Kobayashi
Hiroyuki
H
Yasuda
Shinji
S
Iwasa
Masamitsu
M
Sumi
Syouhei
S
Kawamura
Itta
I
Yamada
Yoshihisa
Y
Nishigaki
Kazuhiko
K
Takemura
Genzou
G
Fujiwara
Takako
T
Fujiwara
Hisayoshi
H
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
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