title: High dose remifentanil increases myocardial oxidative stress and compromises remifentanil infarct-sparing effects in rats.
abstract: Chronic administration of high dose opioids such as morphine is known to create intracellular oxidative stress via an opioid receptor dependent mechanism and this can interfere with cellular function. This study aimed at examining whether such changes can occur following short term exposure to high concentration of remifentanil, a potent short acting opioid. We conducted a experimental study using rat myocardium and systematically quantified tissue levels of superoxide anions, malondialdehyde (MDA) and nitrotyrosine following exposure to increasing duration (15 min, 1 or 2 h) or escalating doses of remifentanil (1 μg, 5 μg, 10 μg or 20 μg/kg/min). Concurrently the susceptibility of the heart to ischaemia reperfusion injury was assessed under the similar conditions. For any given duration of remifentanil infusion, there was increasing superoxide anions generated as the dose of remifentanil was increased. MDA concentrations were significantly increased when the animal was exposed to 10 μg/kg/min for 2h or 20 μg/kg/min for any duration. There was a trend towards an increased nitrotyrosine concentration with increasing dose of remifentanil, becoming significant when the dose was 20 μg/kg/min. The infarct limiting ability of remifentanil was compromised when the dihydroethidium fluorescence positive cell percentage exceeded 50%, MDA concentration greater than 2 nmol/mg of protein and nitrotyrosine content exceeding 1.5 μg/mg of protein. Short term high dose opioid exposure can induce oxidative changes seen previously only with chronic opioid use and this high oxidative stress environment corrupts the heart's sensitivity to be preconditioned by opioids.
authors: Department of Anaesthesiology, The University of Hong Kong, Hong Kong SAR, China; Attending anaesthesiologist, First Affiliated Hospital, Anhui Medical University, Auhui, China.
authors: Bin
authors: B
authors: Mei
authors: Tingting
authors: T
authors: Wang
authors: Yuan
authors: Y
authors: Wang
authors: Zhengyuan
authors: Z
authors: Xia
authors: Michael G
authors: MG
authors: Irwin
authors: Gordon T C
authors: GT
authors: Wong
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010880:Piperidines / Q000009:adverse effects* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077208:Remifentanil; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D000077208:Remifentanil
keywords: Cardiac protection; Nitrosative stress; Opioids; Oxidative stress; Remifentanil