Research Paper Advance Articles
Remifentanil preconditioning protects against hypoxia-induced senescence and necroptosis in human cardiac myocytes in vitro
- 1 Department of Biotechnology, Institute of Biology and Biotechnology, University of Rzeszow, Rzeszow, Poland
- 2 Anesthesiology and Intensive Care Department with the Center for Acute Poisoning, St. Jadwiga Provincial Clinical Hospital, Rzeszow, Poland
- 3 Clinical Department of Cardiac Surgery, St. Jadwiga Provincial Clinical Hospital, Rzeszow, Poland
- 4 Medical College, University of Rzeszow, Rzeszow, Poland
Received: March 9, 2020 Accepted: June 9, 2020 Published: June 25, 2020https://doi.org/10.18632/aging.103604
How to Cite
Copyright © 2020 Lewinska et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Remifentanil and other opioids are suggested to be protective against ischemia-reperfusion injury in animal models and coronary artery bypass surgery patients, however the molecular basis of such protection is far from being understood. In the present study, we have used a model of human cardiomyocytes treated with the hypoxia-mimetic agent cobalt chloride to investigate remifentanil preconditioning-based adaptive responses and underlying mechanisms. Hypoxic conditions promoted oxidative and nitrosative stress, p21-mediated cellular senescence and the activation of necroptotic pathway that was accompanied by a 2.2-, 9.6- and 8.2-fold increase in phosphorylation status of mixed lineage kinase domain-like pseudokinase (MLKL) and release of pro-inflammatory cytokine IL-8 and cardiac troponin I, a marker of myocardial damage, respectively. Remifentanil preconditioning was able to lower hypoxia-mediated protein carbonylation and limit MLKL-based signaling and pro-inflammatory response to almost normoxic control levels, and decrease hypoxia-induced pro-senescent activity of about 21% compared to control hypoxic conditions. In summary, we have shown for the first time that remifentanil can protect human cardiomyocytes against hypoxia-induced cellular senescence and necroptosis that may have importance with respect to the use of remifentanil to diminish myocardial ischemia and reperfusion injury in patients undergoing cardiac surgery.