Diabetes mellitus mitigates cardioprotective effects of remifentanil preconditioning in ischemia-reperfused rat heart in association with anti-apoptotic pathways of survival
- Authors
- Kim H.S.; Cho J.E.; Hwang K.C.; Shim Y.H.; Lee J.H.; Kwak Y.L.
- Issue Date
- 2010
- Keywords
- Diabetes mellitus; Ischemia-reperfusion; Remifentanil
- Citation
- European Journal of Pharmacology, v.628, no.1-3, pp 132 - 139
- Pages
- 8
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- European Journal of Pharmacology
- Volume
- 628
- Number
- 1-3
- Start Page
- 132
- End Page
- 139
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/15500
- DOI
- 10.1016/j.ejphar.2009.11.032
- ISSN
- 0014-2999
1879-0712
- Abstract
- Diabetes mellitus has been known to mitigate ischemic or pharmacologic preconditioning in ischemia-reperfusion injuries. Remifentanil is a widely used opioid in cardiac anesthesia that possesses a cardioprotective effect against ischemia-reperfusion. We evaluated whether diabetes affected remifentanil preconditioning induced cardioprotection in ischemia-reperfusion rat hearts in view of anti-apoptotic pathways of survival and Ca2+ homeostasis. Streptozotocin-induced, diabetic rats and age-matched wild-type Sprague-Dawley rats were subjected to a left anterior descending coronary artery occlusion for 30 min followed by 1 h of reperfusion. Each diabetic and wild-type rat was randomly assigned to the sham, ischemia-reperfusion only, or remifentanil preconditioning group. Myocardial infarct size, activities of ERK1/2, Bcl2, Bax and cytochrome c, and gene expression influencing Ca2+ homeostasis were assessed. Remifentanil preconditioning significantly reduced myocardial infarct size compared to ischemia-reperfusion only in wild-type rats but not in diabetic rats. Remifentanil preconditioning increased expression of ERK1/2 and anti-apoptotic protein Bcl-2 and decreased expression of pro-apoptotic proteins, Bax and cytochrome c, compared to ischemia-reperfusion only in wild-type rats. In diabetic rat hearts, however, remifentanil preconditioning failed to recover the phosphorylation state of ERK1/2 and to repress apoptotic signaling. In addition, diabetes minimized remifentanil induced modulation of abnormal changes in sarcoplasmic reticulum genes and proteins in ischemia-reperfusion rat hearts. In conclusion, diabetes mitigated remifentanil induced cardioprotection against ischemia-reperfusion, which might be associated with reduced recovery of the activities of proteins involved in anti-apoptotic pathways including ERK1/2 and the abnormal expression of sarcoplasmic reticulum genes as a result of ischemia-reperfusion in rat hearts. © 2009 Elsevier B.V. All rights reserved.
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Collections - 2. Clinical Science > Department of Anesthesiology and Pain Medicine > 1. Journal Articles
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