A novel anti-diabetic drug, miglitol, markedly reduces myocardial infarct size in rabbits

1 We examined whether N-hydroxyethyl-1-deoxynojirimycin (miglitol), a new h uman anti-diabetic drug with effects to inhibit alpha-1,6-glucosidase glyco gen debranching enzyme and reduce the glycogenolytic rate as well as to inh ibit alpha-1,4-glucosidase, could reduce infarct size in the rabbit heart. Rabbits were subjected to 30-min coronary occlusion followed by 48-h reperf usion. 2 The infarct size as a percentage of area at risk was not reduced by pre-i schaemic treatment with 1 mg kg(-1) miglitol (42.7+/-4.0%, n=10) compared w ith the saline control group (41.7+/-2.3%, n=10). However, it was significa ntly and dose-dependently reduced by pre-ischaemic treatment with 5 or 10 m g kg(-1) of miglitol (25.7+/-4.5%, n=10, and 14.6+/-2.4%, n=10, respectivel y) without altering the blood pressure, heart rate or blood glucose level. However, there was no evidence of an infarct-size reducing effect after pre -reperfusion treatment with 10 mg kg(-1) of miglitol (35.0+/-3.0%, n=10). 3 Another 40 rabbits given 1, 5 and 10 mg kg(-1) of miglitol or saline befo re ischaemia (n = 10 in each) were sacrificed at 30 min of ischaemia for bi ochemical analysis. Miglitol preserved significantly the glycogen content, and attenuated significantly the lactate accumulation in a dose dependent m anner in the ischaemic region at 30 min of ischaemia. 4 Pre-ischaemic treatment, but not pre-reperfusion treatment, with miglitol markedly reduced the myocardial infarct size, independently of blood press ure and heart rate. A dose-dependent effect of miglitol on infarct size, gl ycogenolysis and lactate formation suggests that the mechanism may be relat ed to the inhibition of glycogenolysis. Thus, miglitol may be beneficial fo r coronary heart disease as well as diabetes mellitus.