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dc.contributor.advisorWeinberg, Guyen_US
dc.contributor.authorFettiplace, Michael Roberten_US
dc.date.accessioned2017-10-27T23:35:17Z
dc.date.available2017-10-27T23:35:17Z
dc.date.created2017-05en_US
dc.date.issued2017-04-10en_US
dc.date.submittedMay 2017en_US
dc.identifier.urihttp://hdl.handle.net/10027/21830
dc.description.abstractIntravenous lipid emulsion was identified in 1998 as a treatment for local anesthetic toxicity and successfully translated into clinical practice in 2006. As with many drugs, practitioners first used intravenous lipid emulsion without full mechanistic insight. In order to more fully understand the mechanisms underlying the reversal of cardiac pharmacotoxicity, we used in vivo, ex vivo and in silico models to tease apart the mechanisms. We identified a multi-modal mechanism that included a scavenging effect, whereby the new intravenous lipid compartment facilitated an accelerated redistribution of drug from heart (and other toxin sensitive organs) to muscle and liver for storage and detoxification. Second, we identified a benefit to the cardiovascular system that improved blood pressure and cardiac output further improving redistribution. Finally, we found that changes in kinase signaling facilitated these improvements. Lipid emulsion drove pro-survival kinase pathways and improved energy processing to improve outcomes. In summary, the three components provide a comprehensive mechanism to explain the rapid recovery from cardiac pharmacotoxicity by intravenous lipid emulsion.en_US
dc.format.mimetypeapplication/pdfen_US
dc.subjectLipid emulsion, Intralipid, Bupivacaine, local anesthetic, toxicity, pharmacotoxicity, kinase, insulin, inotropy, lusitropy, hemodynamics, overdose, regional anesthesia,en_US
dc.titleA Comprehensive Mechanism for Reversal of Cardiac Pharmacotoxicity by Intravenous Lipid Emulsionen_US
dc.typeThesisen_US
thesis.degree.departmentNeuroscienceen_US
thesis.degree.grantorUniversity of Illinois at Chicagoen_US
thesis.degree.levelDoctoralen_US
thesis.degree.namePhD, Doctor of Philosophyen_US
dc.contributor.committeeMemberFeinstein, Douglasen_US
dc.contributor.committeeMemberBonini, Marceloen_US
dc.contributor.committeeMemberAkpa, Belinda S.en_US
dc.type.materialtexten_US
dc.contributor.chairMinshall, Richarden_US


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