title: Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury and blunts cardioprotective effect of GIK.
abstract: There is a close association between hyperglycemia and increased risk of mortality after acute myocardial infarction (AMI). However, whether acute hyperglycemia exacerbates myocardial ischemia/reperfusion (MI/R) injury remains unclear. We observed the effects of acute hyperglycemia on MI/R injury and on the cardioprotective effect of glucose-insulin-potassium (GIK). Male rats were subjected to 30 min of myocardial ischemia and 6 h of reperfusion. Rats were randomly received one of the following treatments (at 4 ml.kg(-1).h(-1) iv): Vehicle, GIK (GIK during reperfusion; glucose: 200g/l, insulin: 60 U/l, KCL: 60 mmol/l), HG (high glucose during ischemia; glucose:500 g/l), GIK + HG (HG during I and GIK during R) or GIK + wortmannin (GIK during R and wortmannin 15 min before R). Blood glucose, plasma insulin concentration and left ventricular pressure (LVP) were monitored throughout the experiments. Hyperglycemia during ischemia not only significantly increased myocardial apoptosis (23.6 +/- 1.7% vs. 18.8 +/- 1.4%, P < 0.05 vs. vehicle), increased infarct size (IS) (45.6 +/- 3.0% vs. 37.6 +/- 2.0%, P < 0.05 vs. vehicle), decreased Akt and GSK-3beta phosphorylations (0.5 +/- 0.2 and 0.6 +/- 0.1% fold of vehicle, respectively, P < 0.05 vs. vehicle) following MI/R, but almost completely blocked the cardioprotective effect afforded by GIK, as evidenced by significantly increased apoptotic index (19.1 +/- 2.0 vs. 10.3 +/- 1.2%, P < 0.01 vs. GIK), increased myocardial IS (39.2 +/- 2.8 vs. 27.2 +/- 2.1%, P < 0.01 vs. GIK), decreased Akt phosphorylation (1.1 +/- 0.1 vs. 1.7 +/- 0.2%, P < 0.01 vs. GIK) and GSK-3beta phosphorylation (1.4 +/- 0.2 vs. 2.3 +/- 0.2%, P < 0.05 vs. GIK). Hyperglycemia significantly exacerbates MI/R injury and blocks the cardioprotective effect afforded by GIK, which is, at least in part, due to hyperglycemia-induced decrease of myocardial Akt activation.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Su
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Heng
authors.initials: H
authors.lastname: Ma
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zhang
authors.forename: Qiu-Jun
authors.initials: QJ
authors.lastname: Yu
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Wang
authors.forename: Rong-Hua
authors.initials: RH
authors.lastname: Luan
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Jia
authors.forename: Hai-Chang
authors.initials: HC
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000208:Acute Disease; D000818:Animals; D002314:Cardioplegic Solutions / Q000008:administration & dosage; D002316:Cardiotonic Agents / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage; D006943:Hyperglycemia / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D011188:Potassium / Q000008:administration & dosage; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D002314:Cardioplegic Solutions; D002316:Cardiotonic Agents; D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D011188:Potassium