Cardiac Opioid System and Its Role in Heart Failure and Ischemia–Reperfusion Injury

Opioid receptors and peptides act as modulators of cardiac and vascular function. These effects are mediated not only by central mechanisms but also via a local cardiac opioid system, which has gained increasing attention for its potential role in cardiovascular disease and perioperative medicine. In ischemia–reperfusion injury, opioids have been associated with cardioprotective effects in preclinical models and have also been investigated clinically. In contrast, opioid administration in heart failure has been linked to adverse outcomes, including higher in-hospital mortality and an increased need for ventilatory support. Accordingly, opioid effects on cardiac function and hemodynamic regulation are particularly relevant in heart failure. This review provides an overview of the cardiac opioid system, highlights functional differences in heart failure and ischemia–reperfusion injury, and places these mechanistic insights in a clinical context, outlining therapeutic implications and cardiovascular risks of perioperative opioid use.