P L Gambús1, I F Trocóniz2, X Feng3, M Gimenez-Milá4, R Mellado4, V Degos5, S Vacas3, M Maze3. 1. Department of Anesthesia and Perioperative Care, University of California San Francisco (UCSF), San Francisco, CA, USA; Systems Pharmacology Effect Control & Modeling (SPEC-M) Research Group, Anesthesiology Department, Hospital CLINIC de Barcelona, Barcelona, Spain; NeuroImmunology Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Electronic address: plgambus@clinic.ub.es. 2. Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Universidad de Navarra, Pamplona, Spain. 3. Department of Anesthesia and Perioperative Care, University of California San Francisco (UCSF), San Francisco, CA, USA. 4. Systems Pharmacology Effect Control & Modeling (SPEC-M) Research Group, Anesthesiology Department, Hospital CLINIC de Barcelona, Barcelona, Spain. 5. Department of Anesthesia and Perioperative Care, University of California San Francisco (UCSF), San Francisco, CA, USA; Department of Anesthesiology and Critical Care, Hôpital Pitié Salpetrière, Assistance Publique-Hopitaux de Paris (APHP), Université Pierre et Marie Curie-Paris VI and UMR INSERM 1141, Paris, France.
Abstract
INTRODUCTION: The relationship between persistent postoperative cognitive decline and the more common acute variety remains unknown; using data acquired in preclinical studies of postoperative cognitive decline we attempted to characterize this relationship. METHODS: Low capacity runner (LCR) rats, which have all the features of the metabolic syndrome, were compared postoperatively with high capacity runner (HCR) rats for memory, assessed by trace fear conditioning (TFC) on the 7th postoperative day, and learning and memory (probe trial [PT]) assessed by the Morris water-maze (MWM) at 3 months postoperatively. Rate of learning (AL) data from the MWM test, were estimated by non-linear mixed effects modeling. The individual rat's TFC result at postoperative day (POD) 7 was correlated with its AL and PT from the MWM data sets at postoperative day POD 90. RESULTS: A single exponential decay model best described AL in the MWM with LCR and surgery (LCR-SURG) being the only significant covariates; first order AL rate constant was 0.07 s(-1) in LCR-SURG and 0.16s(-1) in the remaining groups (p<0.05). TFC was significantly correlated with both AL (R=0.74; p<0.0001) and PT (R=0.49; p<0.01). CONCLUSION: Severity of memory decline at 1 week after surgery presaged long-lasting deteriorations in learning and memory.
INTRODUCTION: The relationship between persistent postoperative cognitive decline and the more common acute variety remains unknown; using data acquired in preclinical studies of postoperative cognitive decline we attempted to characterize this relationship. METHODS: Low capacity runner (LCR) rats, which have all the features of the metabolic syndrome, were compared postoperatively with high capacity runner (HCR) rats for memory, assessed by trace fear conditioning (TFC) on the 7th postoperative day, and learning and memory (probe trial [PT]) assessed by the Morris water-maze (MWM) at 3 months postoperatively. Rate of learning (AL) data from the MWM test, were estimated by non-linear mixed effects modeling. The individual rat's TFC result at postoperative day (POD) 7 was correlated with its AL and PT from the MWM data sets at postoperative day POD 90. RESULTS: A single exponential decay model best described AL in the MWM with LCR and surgery (LCR-SURG) being the only significant covariates; first order AL rate constant was 0.07 s(-1) in LCR-SURG and 0.16s(-1) in the remaining groups (p<0.05). TFC was significantly correlated with both AL (R=0.74; p<0.0001) and PT (R=0.49; p<0.01). CONCLUSION: Severity of memory decline at 1 week after surgery presaged long-lasting deteriorations in learning and memory.
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