title: N-methyl-1-deoxynojirimycin (MOR-14), an alpha-glucosidase inhibitor, markedly improves postischemic left ventricular dysfunction.
abstract: We examined whether pharmacological inhibition of glycogenolysis by N-methyl-1-deoxynojirimycin (MOR-14), a new compound which reduces the glycogenolytic rate by inhibiting the alpha-1,6-glucosidase activity of the glycogen-debranching enzyme, can protect the heart against postischemic left ventricular dysfunction. The hearts of male Sprague-Dawley rats were excised, and perfused on a Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O2 and 5% CO2. The hearts were paced at 320 beats/min except during the ischemia. Left ventricular developed pressure (LVDP, mmHg), +/-dP/dt (mmHg/s), and coronary flow (ml/min) were continuously monitored. All hearts were perfused for a total of 120 min including a 30-min preischemic period followed by a 30-min episode of global ischemia and 60 min reperfusion. with or without 0.5 or 2 mM of MOR-14 during the 30-min preischemic period or the first 30 min of reperfusion. In another series of experiments, the myocardial content of glycogen and lactate was measured during the 30-min episode of ischemia in groups treated with and without 2mM of MOR-14. Preischemic but not postischemic treatment with MOR-14 significantly improved LVDP and +/-dP/dt without altering coronary flow during reperfusion in a dose-dependent manner. MOR-14 significantly preserved the glycogen content and significantly attenuated the lactate accumulation during the 30-min episode of ischemia. Preischemic treatment with MOR-14 is protective against postischemic left ventricular dysfunction through the inhibition of glycogenolysis in the isolated rat heart.
authors.affiliation: Second Department of Internal Medicine, Gifu University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nishida
authors.forename: S
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: M
authors.initials: M
authors.lastname: Arai
authors.forename: G
authors.initials: G
authors.lastname: Takemura
authors.forename: Y
authors.initials: Y
authors.lastname: Uno
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.forename: X H
authors.initials: XH
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Fujiwara
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006003:Glycogen / Q000737:chemistry; D065089:Glycoside Hydrolase Inhibitors; D006321:Heart / Q000187:drug effects; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications*; D015425:Myocardial Reperfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D017485:1-Deoxynojirimycin; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; C033424:N-methyldeoxynojirimycin