1 / 6

Roderic G. Eckenhoff, MD Dept. Anesthesiology & Critical Care, University of Pennsylvania

Roderic G. Eckenhoff, MD Dept. Anesthesiology & Critical Care, University of Pennsylvania roderic.eckenhoff@uphs.upenn.edu. Disclosure: No conflicts. Background: Durable post-operative cognitive decline in older people. Positive odds ratio for Alzheimer disease and prior surgery.

vlad
Download Presentation

Roderic G. Eckenhoff, MD Dept. Anesthesiology & Critical Care, University of Pennsylvania

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Roderic G. Eckenhoff, MD Dept. Anesthesiology & Critical Care, University of Pennsylvania roderic.eckenhoff@uphs.upenn.edu Disclosure: No conflicts • Background: • Durable post-operative cognitive decline in older people. • Positive odds ratio for Alzheimer disease and prior surgery. • Biophysical basis for enhanced protein oligomerization. Hypothesis:Inhaled anesthetics promote aggregation and toxicity of disease-associated peptides, and thereby accelerate the onset of neurodegenerative disorders, like Alzheimers. • Methods: • In vitro protein studies – Aβ.1-40 and Aβ1-42 . • Cell culture models – exogenous and endogenous. • Transgenic animal models of enhanced Aβ expression.

  2. Isolated proteins Anesthesiology 2004;101:703 Current Alzheimer Research 2007 (in press)

  3. † # * * LDH release, % change from control * * † # * Cell Culture Anesthesiology 2004;101:703

  4. WT Tg C H I C H I Animals: Tg2576

  5. Impact of Prior Anesthesia History on ADSilber & Rosenbaum analysis of Bohnen papers P=0.11 one sided P=0.08 one sided

  6. Conclusions: • Inhaled anesthetics accelerate aggregation of Aβ. Halo>Iso • Inhaled anesthetics stabilize the toxic Aβ oligomer. • Aβ plus anesthetic is more cytotoxic than either alone. • Inhaled anesthetics enhance plaque in transgenic mouse brain. • Isoflurane causes learning/memory impairment in old WT mice. • Future directions: • Rank-order effects for all these actions. • Effects at pre-symptomatic stage. • Large epidemiologic studies. • Biomarker studies.

More Related