Cardioprotective effect of peptide and non-peptide opioid receptor agonists in cardiac reperfusion: potential clinical application of experimental data

Abstract

Mortality in patients with acute myocardial infarction is 5–8 % and has not decreased in recent years. One of the causes of death is reperfusion cardiac injury. It is quite obvious that there is an urgent need to develop drugs that can effectively reduce mortality in AMI. Opioids could become such drugs. The activation of peripheral µ2-, δ2-, κ1- opioid receptors reduces in infarct size and improves contractility in reperfusion. Peripheral µ1-, δ1-, κ2-receptors are not involved in the regulation of cardiac tolerance to reperfusion cardiac injury. Opioid postconditioning limits myocardial inflammation, reduces microvascular obstruction, inhibits apoptosis of cardiomyocytes and mitigates adverse postinfarction remodeling. Opioids can reduce excess reactive oxygen species production in the reperfused myocardium. The most promising drugs may be opioid peptides that do not penetrate the blood-brain barrier and therefore, unlike other opioids, do not cause nausea, vomiting, and respiratory depression.

Keywords

• opioids
• heart
• reperfusion injury
• infarct size
• contractility
• remodeling
• inflammation
• apoptosis
• reactive oxygen species