Remifentanil but not sufentanil induces cardioprotection in human ischemic heart muscle in vitro

• Published in: BMC pharmacology & toxicology Vol. 24; no. 1; p. 25
• Main Authors: Kunecki, Marcin, Oleksy, Tomasz, Martynów, Jan, Zygmunt, Michalina, Deja, Marek, Kargul, Tomasz, Biernat, Jolanta, Podolec, Piotr, Gołba, Krzysztof S, Płazak, Wojciech
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20-04-2023; BioMed Central
• Subjects: Amplitudes; Analysis; Animal models; Animals; Appendages; Atria; Carbon dioxide; Cardiac muscle; Cardiac patients; Cardiomyocytes; Cardiovascular disease; Coronary artery; Coronary artery bypass; Experiments; Heart; Human rights; Humans; Hypoxia; Ischemia; Ischemic Preconditioning, Myocardial; Medical research; Medicine, Experimental; Morphine; Muscle contraction; Muscles; Myocardium; Narcotics; Norepinephrine; Norepinephrine - pharmacology; Opioid receptors; Patients; Remifentanil; Remifentanil - pharmacology; Reperfusion; Software; Sufentanil; Surgery; Variance analysis; Sufentanil; Cardioprotection; Ischemia–reperfusion injury; remifentanil
• DOI: 10.1186/s40360-023-00660-3
• EISSN: 2050-6511

Previous studies on animal models have suggested that δ-opioid receptor (OR) signaling is the primary pathway responsible for opioids' cardioprotective effect. We hypothesize that the μ-OR's activation protects the human heart muscle.
We performed the experiments on muscular trabeculae obtained from the right atrial appendages of 104 consecutive patients subjected to coronary artery bypass surgery. Two trabeculae from each patient were studied simultaneously and exposed to 60 min of hypoxia with subsequent 60 min of reoxygenation. Remifentanil (5 μM or 50 μM) or sufentanil (40 μM or 400 μM) was used from the time of reoxygenation. Trabeculae contractility was assessed as the maximal amplitude of the contraction at baseline, after 60 min of hypoxia, during reoxygenation, and after norepinephrine application.
During reperfusion, the application of remifentanil improved cardiomyocytes' function as compared to the control group (time from reperfusion: 15 min: 39.8% vs. 21.7%, p = 0.01; 30 min: 41.4% vs. 21.8%, p = 0.01; 60 min: 42.7% vs. 26.9%, p = 0.04; after norepinephrine: 64.7% vs. 43.2%, p = 0.03). The application of sufentanil did not influence cardiomyocyte function as can be seen when comparing the results of the experimental and control group.
Remifentanil, but not sufentanil, induces a cardioprotective effect on human right atria muscle in in vitro conditions, manifested as the increased amplitude of their contraction during reperfusion after 60 min of ischemia.