Diabetes mellitus mitigates cardioprotective effects of remifentanil preconditioning in ischemia-reperfused rat heart in association with anti-apoptotic pathways of survival

Hyun Soo Kim, Jang-Eun Cho, Ki Chul Hwang, Yeon Hee Shim, Jung Hwa Lee, Young Lan Kwak

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)132-139
Number of pages8
JournalEuropean Journal of Pharmacology
Volume628
Issue number1-3
DOIs
Publication statusPublished - 2010 Feb 25
Externally publishedYes

Fingerprint

Reperfusion
Diabetes Mellitus
Ischemia
Apoptosis Regulatory Proteins
Sarcoplasmic Reticulum
Cytochromes c
Homeostasis
Myocardial Infarction
remifentanil
MAP Kinase Signaling System
Coronary Occlusion
Streptozocin
Reperfusion Injury
Opioid Analgesics
Sprague Dawley Rats
Coronary Vessels
Proteins
Anesthesia
Phosphorylation
Gene Expression

Keywords

  • Diabetes mellitus
  • Ischemia-reperfusion
  • Remifentanil

ASJC Scopus subject areas

  • Pharmacology

Cite this

Diabetes mellitus mitigates cardioprotective effects of remifentanil preconditioning in ischemia-reperfused rat heart in association with anti-apoptotic pathways of survival. / Kim, Hyun Soo; Cho, Jang-Eun; Hwang, Ki Chul; Shim, Yeon Hee; Lee, Jung Hwa; Kwak, Young Lan.

In: European Journal of Pharmacology, Vol. 628, No. 1-3, 25.02.2010, p. 132-139.

Research output: Contribution to journalArticle

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