Remifentanil Preconditioning Attenuates Hepatic Ischemia-Reperfusion Injury in Rats via Neuronal Activation in Dorsal Vagal Complex

Abstract

Remifentanil, an ultra-short acting opiate, has been reported to protect against hepatic ischemia-reperfusion injury, which is a major cause of postoperative liver dysfunction. The objective of this study was to determine whether a central vagal pathway is involved in this protective procedure. Rat models of hepatic ischemia-reperfusion were used in the experimental procedures. The results revealed that intravenous pretreatment with remifentanil decreased serum aminotransferases and hepatic histologic damage; however, an intraperitoneal injection of μ-opioid receptor antagonist did not abolish the protection of remifentanil preconditioning. c-Fos immunofluorescence of the brain stem showed that dorsal motor nucleus of the vagus was activated after remifentanil preconditioning. Moreover, serum alanine aminotransferase, histopathologic damage, and apoptosis decreased in remifentanil preconditioning group compared to vagotomized animals with remifentanil preconditioning, and there was no statistical difference of TNF-α and IL-6 between NS/Va and RPC/Va groups. In addition, remifentanil microinjection into dorsal vagal complex decreased serum aminotransferases, inflammatory cytokines, and hepatic histologic injury and apoptosis, and these effects were also abolished by a peripheral hepatic vagotomy. In conclusion, remifentanil preconditioning conferred liver protection against ischemia-reperfusion injury, which was mediated by the central vagal pathway.

Evaluation of the effects of esmolol and remifentanil for controlled hypotension application on hemodynamics and oxidative stress parameters

“…Furthermore, owing to its molecular structure, remifentanil primarily circulates in nonionized areas, and its liposoluble structure helps it in penetrating the blood-brain barrier and reaching a balance in this area. 13,14 Cui Cui et al designed an animal study to determine whether remifentanil provides protection against hepatic IRI through the activation of the μ-opioid receptor, and, if so, to determine whether the vagus nerve was involved in this process. In this study, it has been shown that, with hepatic preconditioning, remifentanil provides protection against IRI by activating the central vagus nerve instead of peripheral μ-opioid receptors.…”

Opioids Preconditioning Upon Renal Function and Ischemia-Reperfusion Injury: A Narrative Review

“…Similarly, remifentanil suppresses the apoptotic pathways blocking the association of TNF-α to its receptor [113]. Opioids are also strongly related to the protection from IRI in other tissues such as the liver [114,115], endothelium [116] and skeletal muscle [117,118] and involve similar mechanisms of action.…”

Remifentanil repairs cartilage damage and reduces the degradation of cartilage matrix in post-traumatic osteoarthritis, and inhibits IL-1β-induced apoptosis of articular chondrocytes via inhibition of PI3K/AKT/NF-κB phosphorylation

“…RFT is an ultra-short acting opioid that is rapidly degraded in the plasma and tissue by nonspecific esterases (7), and thus, has been used as an adjuvant analgesic for general anesthesia (8). It has also been shown to have a protective effect against hepatic ischemia-reperfusion injury (9). In human keratinocytes, RFT improves hydrogen peroxideinduced oxidative injury (10).…”