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Remifentanil Preconditioning Protects against Ischemic Injury in the Intact Rat Heart

Background: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. Methods: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 × 3) or pretreatment with remifentanil, performed with the same regime (3 × 5-min infusions) using 0.2, 0.6, 2, 6, or 20 μg·kg−1·min−1 intravenously. The experiment was repeated with naltrindole (a selective Δ-opioid receptor antagonist, 5 mg/kg), nor-binaltorphimine (a selective &kgr;-OR antagonist, 5 mg/kg), or CTOP (a selective μ-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. Results: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 μ, &kgr;, or Δ-opioid antagonist. The infarct-sparing effect of ischemic preconditioning was abolished by blockade of &kgr;-opioid receptors or Δ-opioid receptors but not by μ-opioid receptors. Conclusion:Remifentanil mimics cardioprotection via all three opioid receptors. This differs from ischemic preconditioning, which confers cardioprotection via &kgr;- and Δ-, but not μ-opioid receptors. Part of the protective effect of remifentanil may be produced by μ-agonist activity outside the heart.