title: Repetitive postprandial hyperglycemia increases cardiac ischemia/reperfusion injury: prevention by the alpha-glucosidase inhibitor acarbose.
abstract: Protective effects of the alpha-glucosidase inhibitor acarbose have been reported for various diabetic complications. In the STOP-NIDDM study, even patients without overt diabetes, but with impaired glucose tolerance, had a reduction in cardiovascular events when treated with acarbose. Therefore, we investigated the effect of repetitive postprandial hyperglycemia on the cardiac ischemia/reperfusion injury in vivo. Mice were treated daily by single applications of placebo, sucrose (4 g/kg body weight), or sucrose + acarbose (10 mg/kg body weight) by gavage for 7 days. Acarbose treatment significantly reduced the sucrose-induced increase in plasma glucose concentration. Subsequently, animals underwent 30 min of ischemia by coronary artery ligation and 24 h of reperfusion in vivo. In the sucrose group, ischemia/reperfusion damage was significantly increased (infarct/area at risk, placebo vs. sucrose, 38.8+/-7.5% vs. 62.2+/-4.8%, P<0.05). This was prevented by acarbose treatment (infarct/area at risk 30.7+/-7.2%). While myocardial inflammation was similar in all groups, oxidative stress as indicated by a significant increase in lipid peroxides was enhanced in the sucrose, but not in the sucrose + acarbose group. In summary, repetitive postprandial hyperglycemia increases ischemia/reperfusion damage. This effect can be prevented by treatment with the alpha-glucosidase inhibitor acarbose.
authors.affiliation: Medizinische Klinik der Universität Würzburg, Würzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Frantz
authors.forename: Laura
authors.initials: L
authors.lastname: Calvillo
authors.forename: Jochen
authors.initials: J
authors.lastname: Tillmanns
authors.forename: Inka
authors.initials: I
authors.lastname: Elbing
authors.forename: Charlotte
authors.initials: C
authors.lastname: Dienesch
authors.forename: Hilmar
authors.initials: H
authors.lastname: Bischoff
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
mesh_terms: D020909:Acarbose / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003250:Constriction; D003331:Coronary Vessels; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005502:Food; D065089:Glycoside Hydrolase Inhibitors; D006943:Hyperglycemia / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012008:Recurrence
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D017382:Reactive Oxygen Species; D020909:Acarbose