The anti-diabetic
drug miglitol, an
alpha-glucosidase inhibitor, which is currently used clinically, reduces
myocardial infarct size by reducing the glycogenolytic rate through inhibition of the alpha-1,6-glucosidase of
glycogen-debranching enzyme in the heart.
Nicorandil, a K(
ATP) 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 microg 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 microg kg(-1) min(-1) 5 min), and 10 mg kg(-1) of
miglitol and
nicorandil (100 microg 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 K(
ATP) channels.