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dc.contributor.authorKenny, Jonathan D.
dc.contributor.authorChemali, Jessica J.
dc.contributor.authorCotten, Joseph F.
dc.contributor.authorVan Dort, Christa J.
dc.contributor.authorTaylor, Norman E.
dc.contributor.authorBrown, Emery N.
dc.contributor.authorSolt, Ken
dc.contributor.authorKim, Seong-Eun
dc.contributor.authorBa, Demba E
dc.date.accessioned2017-12-08T15:35:54Z
dc.date.available2017-12-08T15:35:54Z
dc.date.issued2016-11
dc.identifier.issn0003-2999
dc.identifier.urihttp://hdl.handle.net/1721.1/112652
dc.description.abstractBACKGROUND: Although emergence from general anesthesia is clinically treated as a passive process driven by the pharmacokinetics of drug clearance, agents that hasten recovery from general anesthesia may be useful for treating delayed emergence, emergence delirium, and postoperative cognitive dysfunction. Activation of central monoaminergic neurotransmission with methylphenidate has been shown to induce reanimation (active emergence) from general anesthesia. Cholinergic neurons in the brainstem and basal forebrain are also known to promote arousal. The objective of this study was to test the hypothesis that physostigmine, a centrally acting cholinesterase inhibitor, induces reanimation from isoflurane anesthesia in adult rats. METHODS: The dose-dependent effects of physostigmine on time to emergence from a standardized isoflurane general anesthetic were tested. It was then determined whether physostigmine restores righting during continuous isoflurane anesthesia. In a separate group of rats with implanted extradural electrodes, physostigmine was administered during continuous inhalation of 1.0% isoflurane, and the electroencephalogram changes were recorded. Finally, 2.0% isoflurane was used to induce burst suppression, and the effects of physostigmine and methylphenidate on burst suppression probability (BSP) were tested. RESULTS: Physostigmine delayed time to emergence from isoflurane anesthesia at doses ≥0.2 mg/kg (n = 9). During continuous isoflurane anesthesia (0.9% ± 0.1%), physostigmine did not restore righting (n = 9). Blocking the peripheral side effects of physostigmine with the coadministration of glycopyrrolate (a muscarinic antagonist that does not cross the blood-brain barrier) produced similar results (n = 9 each). However, during inhalation of 1.0% isoflurane, physostigmine shifted peak electroencephalogram power from δ ( < 4 Hz) to θ (4-8 Hz) in 6 of 6 rats. During continuous 2.0% isoflurane anesthesia, physostigmine induced large, statistically significant decreases in BSP in 6 of 6 rats, whereas methylphenidate did not. CONCLUSIONS: Unlike methylphenidate, physostigmine does not accelerate time to emergence from isoflurane anesthesia and does not restore righting during continuous isoflurane anesthesia. However, physostigmine consistently decreases BSP during deep isoflurane anesthesia, whereas methylphenidate does not. These findings suggest that activation of cholinergic neurotransmission during isoflurane anesthesia produces arousal states that are distinct from those induced by monoaminergic activation.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant TR01-GM104948)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant DP1-OD003646)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant K08-GM094394)en_US
dc.publisherOvid Technologies (Wolters Kluwer Health)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1213/ANE.0000000000001234en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titlePhysostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Ratsen_US
dc.typeArticleen_US
dc.identifier.citationKenny, Jonathan D. et al. “Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Rats.” Anesthesia & Analgesia 123, 5 (November 2016): 1210–1219 © 2016 International Anesthesia Research Societyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentPicower Institute for Learning and Memoryen_US
dc.contributor.mitauthorKim, Seong-Eun
dc.contributor.mitauthorBa, Demba E
dc.relation.journalAnesthesia & Analgesiaen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2017-12-07T19:28:27Z
dspace.orderedauthorsKenny, Jonathan D.; Chemali, Jessica J.; Cotten, Joseph F.; Van Dort, Christa J.; Kim, Seong-Eun; Ba, Demba; Taylor, Norman E.; Brown, Emery N.; Solt, Kenen_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-4518-4208
mit.licenseOPEN_ACCESS_POLICYen_US
mit.metadata.statusComplete


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