Opioids i.e., compounds with morphine–like actions, and their receptors have been demonstrated to be involved in cardioprotection,
at least in scientific studies, which makes sense as cardiomyocytes express most of the known opioid receptors and their agonists.
In vitro and in vivo studies have demonstrated that the opioid system plays various important roles in maintaining cardiac function; i.e., it
influences cardiac rhythm, cell stress, and even developmental processes. In support of these research findings, there is also good clinical
evidence that opioids are effective as cardioprotective drugs. In fact, in the American College of Cardiology Foundation/American Heart
Association (ACCF/AHA) guidelines for coronary artery bypass graft surgery opioids and volatile halogenated anesthetics are referred to
as anti-ischemic or conditioning agents. Although opioids are administered to all patients who undergo surgery as well as patients admitted
to the ICU, including those that suffer heart attacks, no recommendations about their use for the preconditioning/management of
myocardial ischemia have been included in recent clinical guidelines due to the weak clinical evidence about their effects. Opioids have
been used as pain control agents in the clinical setting for a long time. As such, surgical, critical care, and cancer patients routinely receive
them. On the other hand, ischemic heart disease continues to be a leading cause of morbidity and mortality in developed countries,
and opioid therapy might be useful for treating the condition. This review examines recent clinical trials of the effects of opioids on
ischemic heart disease and discusses the barriers to the use of opioids for cardioprotection.