title: Diabetes mellitus mitigates cardioprotective effects of remifentanil preconditioning in ischemia-reperfused rat heart in association with anti-apoptotic pathways of survival.
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 Ca(2+) homeostasis. Streptozotocin-induced, diabetic rats and age-matched wild-type Sprague-Dawley rats were subjected to a left anterior descending coronary artery occlusion for 30min followed by 1h 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 Ca(2+) 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.
authors: Department of Life Science, College of Natural Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors: Hyun Soo
authors: HS
authors: Kim
authors: Jang Eun
authors: JE
authors: Cho
authors: Ki Chul
authors: KC
authors: Hwang
authors: Yeon Hee
authors: YH
authors: Shim
authors: Jung Hwa
authors: JH
authors: Lee
authors: Young Lan
authors: YL
authors: Kwak
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077208:Remifentanil; D015427:Reperfusion Injury / Q000517:prevention & control*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D010880:Piperidines; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000077208:Remifentanil