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LUNG-PROTECTIVE MECHANICAL VENTILATION FOR 50 HOURS INJURES THE HIPPOCAMPUS

      SESSION TITLE: Critical Care Posters
      SESSION TYPE: Original Investigation Posters
      PRESENTED ON: October 18-21, 2020
      PURPOSE: To investigate whether 50 hours of lung-protective mechanical ventilation injures the hippocampus.
      METHODS: We compared hippocampal injury between eight mechanically ventilated human-size pigs using lung-protective ventilation settings (MV group) with six never-ventilated human-size pigs (NV group). Lung-protective ventilation settings were defined as: PEEP of 5cmH20, peak pressure less than 30cmH2O and driving pressure less than 15cmH2O. Hippocampal injury markers used were; TUNEL-positive hippocampal cells (MV group n=8, NV group n=6) and prevalence of neuron specific enolase (NSE) in the hippocampus (MV group n=4, NV group n=6). In each group, 21 fields of similar size and similar total area were analyzed. Machine-learning software (ImageJ) was used to count TUNEL-positive hippocampal cells, and also to measure the presence of NSE in the hippocampus. The percentage of TUNEL-positive cells in the hippocampus was then calculated. Statistical analysis was made using PRISM software.
      RESULTS: The percentage of TUNEL-positive cells found in the dentate gyrus (DG), CA1, and CA3 regions, combined, was significantly higher in the MV group (38; 44,797/117,886) than in the NV group (1; 338/33,805; p<0.001). In the MV group, the percentages of TUNEL-positive cells in the three different hippocampal regions were 41% in the DG, 37% in the CA1 region, and 39% in the CA3 region (p=0.6). The same assay in the NV group showed no significant differences but an overall lower percentage of 1% in the DG, 1% in the CA1 region, and 1% in the CA3 region (p=0.6).The brightness quantification of NSE in the hippocampus was also significantly higher in the MV group (225 a.u.) than in the NV group (218 a.u.; p=0.015) reflecting significantly higher levels of NSE in the MV group.
      CONCLUSIONS: Lung-protective mechanical ventilation for 50 hours leads to a higher percentage of TUNEL-positive cells and a greater concentration of NSE in the hippocampus. Both of these are indicative of greater neuronal apoptosis in the MV group. These results indicate that during lung-protective mechanical ventilation significant hippocampal injury is observed.
      CLINICAL IMPLICATIONS: Longer duration of mechanical ventilation has been linked to a higher risk of patients developing cognitive impairment in the intensive care unit. Preclinical studies have shown hippocampal apoptosis and cognitive impairment after mechanical ventilation. In clinical studies, the presence of neuron specific enolase has been associated with cognitive impairment, such as that observed after traumatic brain injury. Our preclinical data suggests that cellular injury mechanisms are active during lung-protective mechanical ventilation. This data could be used in the design of future studies to better understand the development of cognitive impairment after mechanical ventilation.
      DISCLOSURES: Employee relationship with Lungpacer Medical Inc. Please note: $20001 - $100000 Added 01/14/2020 by Thiago Bassi, source=Web Response, value=Grant/Research Support
      Consultant relationship with Lungpacer Medical Inc. Please note: $20001 - $100000 Added 03/19/2020 by Karl Fernandez, source=Web Response, value=Grant/Research Support
      Consultant relationship with Lungpacer Medical Please note: $5001 - $20000 Added 03/26/2020 by Michelle Nicholas, source=Web Response, value=Consulting fee
      No relevant relationships by Marlena Ornowska, source=Web Response
      Also co-applicant on various patents relationship with Lungpacer Medical Inc Please note: $20001 - $100000 Added 03/29/2020 by Steven Reynolds, source=Web Response, value=research support
      Removed 03/29/2020 by Steven Reynolds, source=Web Response
      owns stock relationship with Lungpacer Medical Inc Please note: >$100000 Added 03/29/2020 by Steven Reynolds, source=Web Response, value=as above owns stock
      Collaborative research relationship with Lungpacer Medical Inc Please note: $20001 - $100000 Added 03/29/2020 by Steven Reynolds, source=Web Response, value=Grant/Research Support
      Scientific Medical Advisor relationship with Lungpacer Medical Inc Please note: $20001 - $100000 Added 03/31/2020 by Steven Reynolds, source=Web Response, value=Consulting fee
      researcher relationship with Lungpacer Medical Inc Please note: $20001 - $100000 Added 03/31/2020 by Steven Reynolds, source=Web Response, value=Grant/Research Support
      Own shares relationship with Lungpacer Medical Inc Please note: >$100000 Added 03/31/2020 by Steven Reynolds, source=Web Response, value=own shares
      Consultant relationship with Lungpacer Medical Inc. Please note: $5001 - $20000 Added 03/19/2020 by Elizabeth Rohrs, source=Web Response, value=Consulting fee