The Effects of the Toll-Like Receptor 4 Antagonist, Ibudilast, on Sevoflurane's Minimum Alveolar Concentration and the Delayed Remifentanil-Induced Increase in the Minimum Alveolar Concentration in Rats. (May 2016)

• Record Type: Journal Article
• Authors: Ruiz-Pérez, Daniel; Benito, Javier; Polo, Gonzalo; Largo, Carlota; Aguado, Delia; Sanz, Luis; Gómez de Segura, Ignacio A.
• Is Part Of: Anesthesia & analgesia. Volume 122:Number 5(2016)
• Publication Date: 2016-05
• Subjects: Anesthesiology -- Periodicals; Anesthesia; Anesthesiology; Analgesia; Analgesics; Anesthesiology -- Periodicals; 617.9605
• DOI: 10.1213/ANE.0000000000001171
• Languages: English
• ISSNs: 0003-2999

Abstract

Abstract : BACKGROUND: Ultralow doses of naloxone, an opioid and toll-like receptor 4 antagonist, blocked remifentanil-induced hyperalgesia and the associated increase in the minimum alveolar concentration (MAC), but not tolerance. The aim was to determine the effects of the toll-like receptor 4 antagonist, ibudilast, on the MAC in the rat and how it might prevent the effects of remifentanil. METHODS: Male Wistar rats were randomly allocated to 5 treatment groups ( n = 7 per group): 10 mg/kg ibudilast intraperitoneally, 240 µg/kg/h remifentanil IV, ibudilast plus remifentanil, remifentanil plus naloxone IV, or saline. The sevoflurane MAC was determined 3 times in every rat and every day (days 0, 2, and 4): baseline (MAC-A) and 2 further determinations were made after treatments, 1.5 hours apart (MAC-B and MAC-C). RESULTS: A reduction in baseline MAC was produced on day 0 by ibudilast, remifentanil, remifentanil plus ibudilast, remifentanil plus naloxone ( P < 0.01), but not saline. Similar effects were found on days 2 and 4. A tolerance to remifentanil was found on days 0, 2, and 4, which neither ibudilast nor naloxone prevented. The MAC increase produced by remifentanil on day 4 ( P = 0.001) was prevented by either ibudilast or naloxone. CONCLUSIONS: Ibudilast, besides reducing the MAC, prevented the delayed increase in baseline MAC produced by remifentanil but not the increase in MAC caused by tolerance to remifentanil. Abstract : Supplemental Digital Content is available in the text.Published ahead of print February 8, 2016