Page 1 of 33 Articles in PresS. Am J Physiol Endocrinol Metab (May 22, 2007). doi:10.1152/ajpendo.00221.2007
Acute hyperglycemia exacerbates myocardial ischemia /reperfusion injury and blunts cardioprotective effect of GIK Hui Su1,2†, Xin Sun3†, Heng Ma4†, Hai-Feng Zhang4, Qiu-Jun Yu4, Chen Huang2, Xiao-Ming Wang2, Rong-Hua Luan1, Guo-Liang Jia1, Hai-Chang Wang1*, Feng Gao4* (1Department of Cardiology, 2 Department of Geriatrics,
3
Department of Pediatrics, Xijing
Hospital, 4Department of Physiology, Fourth Military Medical University, Xi’an 710032, China)
†
These authors contributed equally to this study
Running Title: Hyperglycemia and myocardial ischemic/reperfused injury Word Count: 5672
Correspondence to: *Feng Gao, M.D., Ph.D. Department of Physiology and Department of Cardiology Xijing Hospital, Fourth Military Medical University Xi’an 710032, China E-mail:
[email protected] Tel: 86-29-84776423 Fax: 86-29-84776423 or to: *Hai-Chang Wang, M.D., Ph.D. Department of Cardiology, Xijing Hospital Fourth Military Medical University Tel: 86-29-84775183 Fax: 86-29-84775183 E-mail:
[email protected]
1
Copyright © 2007 by the American Physiological Society.
Page 2 of 33
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 minutes of myocardial ischemia and 6 hours of reperfusion. Rats were randomly received one of the following treatmentsዊi.v. infusion at 4 ml·kg-1·h-1): 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 plus HG (HG during I and GIK during R) or GIK plus wortmannin (GIK during R and wortmannin 15 mins 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
