Opioid-induced Cardioprotection

Abstract

Ischemic heart disease and myocardial infarction continue to be leading causes of cardiovascular morbidity and mortality. Activation of opioid, adenosine, bradykinin, adrenergic and other G-protein coupled receptors have been found to be cardioprotective. κ- and/or δ-opioid receptor activation is involved in direct myocardial protection, while the role of μ-opioid receptors seems less clear. In addition, differential affinities to the three opioid-receptor subtypes by various agonists and cross-talk among different G-protein coupled receptors render conclusions regarding opioid-mediated cardioprotection challenging. The present review will focus on the protective effects of endogenously released opioid peptides as well as exogenously administered opioids such as morphine, fentanyl, remifentanil, butorphanol, and methadone against myocardial ischemia/reperfusion injury. Receptor heterodimerization and cross-talk as well as interactions with other cardioprotective techniques will be discussed. Implications for opioid-induced cardioprotection in humans and for future drug development to improve myocardial salvage will be provided.

Effect and Safety of Morphine Use in Acute Anterior ST‐Segment Elevation Myocardial Infarction

“…Myocardial protection with opioid use has been inconsistently reported. Several studies suggest a cardioprotective effect especially with morphine in the surgical context of coronary artery bypass graft, but these studies were conducted in small surgical patient populations and assessed indirect outcomes 20, 21. In STEMI patients undergoing PPCI, a cardioprotective effect could be demonstrated for morphine in addition to the basal effect of remote ischemic conditioning,22 but no additional myocardial protection was observed with fentanyl in patients undergoing elective PPCI 23…”

Side effects of pain and analgesia in animal experimentation

“…Endogenously released opioid peptides, as well as exogenously administered opioids, can have cardioprotective effects 43 . For example, in rodent ischemia reperfusion experiments, reduced infarct size was seen after preconditioning with fentanyl 44 .…”

Opioid-Induced Cardioprotection against Ischemia-Reperfusion Injury: The Challenge in Diabetes

“…Opioid receptors (ORs) are classified into four major types, including the mu (µ), delta (δ), kappa (κ) and OR-like subtype1 receptor (ORL-1). The structures and functions of these four opioid receptor subtypes are well described by other reviews [14][15][16]. ORs are G-protein-coupled receptors [17].…”