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.