The anti-diabetic drug miglitol is protective against anginal ischaemia through a mechanism independent of regional myocardial blood flow in the dog.
1. In the present study, we attempted to clarify whether the antidiabetic drug miglitol, an alpha-glucosidase inhibitor, has a protective effect against anginal ischaemia. We had reported previously that miglitol reduces myocardial infarct size through inhibition of glycogenolysis during ischaemia in rabbits. However, the effect of miglitol on anginal ischaemia remains unknown. 2. In open-chest beagle dogs with a severely stenosed left anterior descending coronary artery, an epicardial electrode was attached to the surface of the risk area of the left ventricle and a microdialysis probe was implanted into the myocardium to measure ST segment changes and interstitial lactate accumulation. The first episode of anginal ischaemia was induced by atrial pacing and phenylephrine infusion (50-100 microg/min) for 10 min. The second episode of anginal ischaemia was induced 210 min after the first episode. Miglitol (10 mg/kg, i.v.) was administered to the miglitol group (n = 10) 30 min before the second episode of anginal ischaemia, whereas saline was administered to the control group (n = 10). Regional myocardial blood flow was measured using coloured microspheres. 3. There was no significant difference in regional myocardial blood flow in the risk and non-risk areas between the first and second episodes of anginal ischaemia and between the miglitol and control groups. During the first and second episodes of anginal ischaemia, the ST segment was decreased to a similar extent in the control group. Although ST segment depression during the first episode of anginal ischaemia was similar in both groups, ST segment depression during the second episode of anginal ischaemia was significantly attenuated in the miglitol-treated group compared with the control group (1.3 +/- 0.4 vs 2.2 +/- 0.4 mV, respectively). Miglitol significantly attenuated myocardial interstitial lactate accumulation in the risk area. 4. In conclusion, in the present study miglitol improved ST segment depression and attenuated the accumulation of myocardial interstitial lactate during anginal ischaemia without altering regional myocardial blood flow. Miglitol has an anti-anginal ischaemia effect via a mechanism that is independent of regional myocardial blood flow.
Uno
Yoshihiro
Y
Department of General Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
Minatoguchi
Shinya
S
Arai
Masazumi
M
Wang
Ningyuan
N
Chen
Xue-Hai
XH
Hashimoto
Kazuaki
K
Lu
Cuanjiang
C
Takemura
Genzou
G
Fujiwara
Hisayoshi
H
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000787:Angina Pectoris / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050112:Imino Pyranoses / Q000097:blood / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D050112:Imino Pyranoses; D007773:Lactates; C045621:miglitol; D017485:1-Deoxynojirimycin; D005944:Glucosamine