Opioid receptors and myocardial protection: do opioid agonists possess cardioprotective effects?

In an in vivo rat model of myocardial infarction, opioid receptor stimulation has been observed to result in a reduction in infarct size similar to that produced by ischaemic preconditioning. The ability of glibenclamide to abolish this effect suggests an involvement of the myocardial ATP-sensitive potassium (K(ATP)) channel. Importantly, it has recently been demonstrated that glibenclamide can completely abolish the protective effects of preconditioning in humans, suggesting that K(ATP) channel opening may be an endogenous protective mechanism in humans. In this article we report recent findings that indicate that opening of the K(ATP) channel is differentially involved in the antinociceptive effect of some opioids, including buprenorphine, morphine and methadone, but not that of others such as fentanyl or levorphanol. We argue that these findings may also be relevant to the effects of opioids in peripheral tissue, such as the myocardium, and that they may have important clinical ramifications. On the basis of our analysis and interpretation of these in vivo data, we speculate that some opioid agonists, notably buprenorphine, may possess previously unrecognised beneficial cardioprotective effects in some groups of patients, including those undergoing coronary artery bypass and those experiencing an acute myocardial infarction.