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Anesthesiology. 2004 Oct;101(4):918-23.

Remifentanil preconditioning protects against ischemic injury in the intact rat heart.

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  • 1Department of Anaesthesiology, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong.



Opioid receptors mediate cardiac ischemic preconditioning. Remifentanil is a new, potent ultra-short-acting phenylpiperidine opioid used in high doses for anesthesia. The authors hypothesize that pretreatment with this drug confers cardioprotection.


Male Sprague-Dawley rats were anesthetized and the chest was opened. All animals were subjected to 30 min of occlusion of the left coronary artery and 2 h of reperfusion. Before the 30-min occlusion, rats received either preconditioning by ischemia (ischemic preconditioning, 5-min occlusion, 5-min reperfusion x 3) or pretreatment with remifentanil, performed with the same regime (3 x 5-min infusions) using 0.2, 0.6, 2, 6, or 20 intravenously. The experiment was repeated with naltrindole (a selective Delta-opioid receptor antagonist, 5 mg/kg), norbinaltorphimine (a selective kappa-OR antagonist, 5 mg/kg), or CTOP (a selective mu-opioid receptor antagonist, 1 mg/kg) administered before remifentanil-induced preconditioning or ischemic preconditioning, respectively. Infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining.


There was a dose-related reduction in infarct size/area at risk after treatment with remifentanil that was similar to that seen with ischemic preconditioning. This effect was prevented or significantly attenuated by coadministration of a mu, kappa, or Delta-opioid antagonist. The infarct-sparing effect of ischemic preconditioning was abolished by blockade of kappa-opioid receptors or Delta-opioid receptors but not by mu-opioid receptors.


Remifentanil mimics cardioprotection via all three opioid receptors. This differs from ischemic preconditioning, which confers cardioprotection via kappa- and Delta-, but not mu-opioid receptors. Part of the protective effect of remifentanil may be produced by mu-agonist activity outside the heart.

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