Remifentanil preconditioning confers delayed cardioprotection in the rat

Department of Anaesthesiology, The University of Hong Kong, Queen Mary Hospital, Room 424, Block K, Pokfulam Road, Hong Kong.
BJA British Journal of Anaesthesia (Impact Factor: 4.85). 12/2007; 99(5):632-8. DOI: 10.1093/bja/aem261
Source: PubMed

ABSTRACT Preconditioning with remifentanil (RPC) provides immediate cardioprotection in rats via all three types of opioid (OP) receptor. This study sought to investigate whether remifentanil also confers delayed cardioprotection via OP receptors.
Male rats received preconditioning either by ischaemia (IPC; 5 min occlusion, 5 min reperfusion x 3) or with remifentanil (RPC; 1, 5, 10, and 20 microg kg(-1) min(-1), 20 min infusion). After 24 h, all animals were subjected to 30 min occlusion of the left coronary artery and 2 h of reperfusion. Subsequently, the time-course effect of RPC (10 microg kg(-1) min(-1), 20 min infusion) was determined at 12, 16, 24, 32, 36, and 48 h intervals, using the same experimental procedure. The effect of RPC (10 microg kg(-1) min(-1), 20 min infusion) and IPC in the presence of selective OP receptor antagonists was evaluated at the 24 h interval. Infarct size (IS), as a percentage of the area at risk (AAR), was determined.
Pre-treatment with remifentanil at 1, 5, 10, and 20 microg kg(-1) min(-1) significantly reduced the IS/AAR at 24 h with the maximum effect at 10 microg kg(-1) min(-1). Remifentanil at 10 microg kg(-1) min(-1) significantly reduced the IS at 12 h [32.5 (sd 9.1)%]; 16 h [26.1 (2.8)%]; 24 h [19.5 (5.0)%]; 32 h [31.2 (9.1)%]; and 36 h [36.4 (9.4)%] after drug administration. The maximal reduction in IS was seen at 24 h and the effect completely disappeared at 48 h [36.4 (9.4)%]. The protective effect of RPC was abolished or significantly attenuated by blockade of any of the three OP receptors with selective antagonists.
Like IPC, remifentanil produces delayed cardioprotection in anaesthetized rats 12-36 h after administration. The protective effect is mediated via all three OP receptors.

5 Reads
  • Source
    • "The IR surgery was performed according to the methods of Zhang et al [15] with modifications. Briefly, rats were anesthetized with sodium pentobarbital (50 mg/kg i.p.), plus additional doses (25 mg/kg i.p.) every 60 min to maintain effective anesthesia [16] and were mechanically ventilated with room air to maintain arterial pH, PCO2 and PO2 within the normal physiological range. The pericardium was opened and a 6-0 silk suture was passed under the left atrial appendage for 2-3 mm through a small polytetrafluoroethylene tube. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies have demonstrated that volatile anesthetic postconditioning confers myocardial protection against ischemia-reperfusion (IR) injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been shown to be impaired in hypercholesterolemia. Therefore, we investigate whether anesthetic-induced cardiac protection was maintained in hypercholesterolemic rats. In the present study, normocholesteolemic or hypercholesterolemic rat hearts were subjected to 30 min of ischemia and 2 h of reperfusion. Animals received 2.4% sevoflurane for 5 min or 3 cycles of 10-s ischemia/10-s reperfusion. The hemodynamic parameters, including left ventricular developed pressure, left ventricular end-diastolic pressure and heart rate, were continuously monitored. The infarct size, apoptosis, p-Akt, p-ERK1/2, p-GSK3β were determined. We found that both sevoflurane and ischemic postconditioning significantly improved heart pump function, reduced infarct size and increased the phosphorylation of Akt, ERK1/2 and their downstream target of GSK3β in the healthy rats. In the hypercholesterolemic rats, neither sevoflurane nor ischemic postconditioning improved left ventricular hemodynamics, reduced infarct size and increased the phosphorylated Akt, ERK1/2 and GSK3β. In contrast, GSK inhibitor SB216763 conferred cardioprotection against IR injury in healthy and hypercholesterolemic hearts. In conclusions, hyperchoesterolemia abrogated sevoflurane-induced cardioprotection against IR injury by alteration of upstream signaling of GSK3β and acute GSK inhibition may provide a novel therapeutic strategy to protect hypercholesterolemic hearts against IR injury.
    PLoS ONE 10/2013; 8(10):e76652. DOI:10.1371/journal.pone.0076652 · 3.23 Impact Factor
  • Source
    • "The cardioprotective mechanisms of R-Pre involve PKC, ERK1/2, and Akt pathways [50-52]. In addition, R-Pre produced delayed cardioprotection in anesthetized rat hearts and this effect was mediated via µ-, δ-, and κ-OPRs [53]. Furthermore, remifentanil-induced postconditioning (R-Post) also protects I/R induced hearts to a similar extent as I-Post which was mediated by both δ- and κ-OPRs [54] while ERK1/2 is involved in R-Post [55]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: During the past few decades, a large number of animal studies demonstrated that commonly used opioids could provide cardioprotection against ischemia-reperfusion (I/R) injury. Opioid-induced preconditioning or postconditioning mimics ischemic preconditioning (I-Pre) or ischemic postconditioning (I-Post). Both δ- and κ-opioid receptors (OPRs) play a crucial role in opioid-induced cardioprotection (OIC). Down stream signaling effectors of OIC include ATP-sensitive potassium (K(ATP)) channels, protein kinase C (PKC), tyrosine kinase, phosphatidylinositol-3-kinase (PI3-kinase), extracellular signal regulated kinase1/2 (ERK1/2), glycogen synthase kinase-3β (GSK-3β), and mitochondrial permeability transition pore (MPTP), among others. Recently, various reports also suggest that opioids could provide cardioprotection in humans. This review will discuss OIC using mostly morphine and remifentanil which are widely used during cardiac anesthesia in addition to the clinical implications of OIC.
    Korean journal of anesthesiology 11/2011; 61(5):358-66. DOI:10.4097/kjae.2011.61.5.358
  • BJA British Journal of Anaesthesia 12/2007; 99(5):603-6. DOI:10.1093/bja/aem276 · 4.85 Impact Factor
Show more