Investigation of mechanism of infarct size-reducing effect of α-1,6-glucosidase inhibitor

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1) N-methyl-1-deoxynojirimycin (NMDM) and α-1,6-glucosidase activity, glyconen and lactateIn an in vitro study of rabbit heart, NMDM inhibited the α-1,6-glucosidase activity in a dose dependent manner. In an in vivo rabbit model, NMDM (100mg/kg, i.v.) inhibited the α-1,6-glucosidase activity without affecting phosphorylase activity during ischemia, and inhibited the breakdown myocardial glycogen and the lactate accumulation.2) NMDM and protein kinase CThe infarct size-reducing effect of NMDM (100 mg/kg, i.v.) was complelely blocked by pretreatment with protein kinase C inhibitor staurosporine (50 μg/kg i.v.). Translocation of the PKC-ε, one of the subtypes of protein kinase C, by NMDM was observed during ischemia by western blotting method.3) NMDM and apoptosisThe percentage of TUNEL-positive myocytes in the infarcted area of the rabbits with 30 min ischemia and 4 hour reperfusion was significantly reduced in the NMDM group (3.8±1.5 %) as compared with control group (10.7±1.9 %).4) NMDM and stunningNMDM (100 mg/kg, i.v.) significantly improved the regional myocardial contractile function in a 10 min-ischemia and reperfusion model of rabbits. This suggests that NMDM improves stunning.