Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury and blunts cardioprotective effect of GIK.
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.
Su
Hui
H
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Sun
Xin
X
Ma
Heng
H
Zhang
Hai-Feng
HF
Yu
Qiu-Jun
QJ
Huang
Chen
C
Wang
Xiao-Ming
XM
Luan
Rong-Hua
RH
Jia
Guo-Liang
GL
Wang
Hai-Chang
HC
Gao
Feng
F
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
D002314:Cardioplegic Solutions; D002316:Cardiotonic Agents; D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D011188:Potassium