Remifentanil preconditioning confers delayed cardioprotection in the rat

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.