Fentanyl protects the heart against ischaemic injury via opioid receptors, adenosine A1 receptors and K(ATP) channel linked mechanisms in rats

Abstract

We have investigated if fentanyl protects against myocardial ischaemic injury and if so, if the mechanism of this protection is mediated via opioid and adenosine A1 receptors, and K(ATP) channels. Langendorff rat hearts were subjected to global ischaemia (30 min) and reperfusion (60 min). The drugs were administered before induction of ischaemia and maintained throughout the experiment. Treatment with fentanyl 740 nmol litre-1 improved post-ischaemic mechanical function, assessed as developed pressure, +dP/dtmax and -dP/dtmin, compared with controls after 60 min of reperfusion. These effects were abolished by naloxone 1 μmol litre-1, DPCPX 10 μmol litre-1, a selective adenosine A1 antagonist and sodium 5-hydroxydecanoate 100 μmol litre-1, a K+(ATP) channel blocker. We conclude that fentanyl protected the heart against post-ischaemic injury by a mechanism which was blocked by an opioid and an adenosine A1 receptor antagonist and also by a K(ATP) channel antagonist.