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TEMPORARY TRANSVENOUS DIAPHRAGM NEUROSTIMULATION THERAPY WITH MECHANICAL VENTILATION MITIGATES ATROPHY IN ALL DIAPHRAGM MYOFIBER TYPES

      SESSION TITLE: Respiratory Care Posters
      SESSION TYPE: Original Investigation Posters
      PRESENTED ON: October 18-21, 2020
      PURPOSE: To expand our current understanding of the use of temporary transvenous diaphragm neurostimulation (TTDN) as a therapy adjunct with mechanical ventilation (MV) to mitigate ventilator-induced diaphragmatic atrophy. This is achieved by using our successful mock ICU pig model and examining the previously unexplored effects of TTDN on the different diaphragm myofiber subclasses. This characterization of the diaphragm involves identifying myofiber subclasses and their associated cross-sectional areas (CSA) in three ventilation conditions: i) MV-Only, ii) MV+TTDN, and iii) never-ventilated, never-paced (NV-NP). The findings of this study could show the continued safe and beneficial use of TTDN to mitigate the atrophic effects on the diaphragm from long-term MV use. MV provides artificial breaths to critically ill patients who are incapable of sustaining normal physiological ventilation. This process is done by “pushing” instead of the normal “pulling” of air into the lungs. The nature of MV negates the normal quiet breathing process by unloading workload from respiratory muscles like the diaphragm, leading to its quiescence. As a result, ventilator-induced diaphragmatic dysfunction (VIDD) with associated muscle atrophy can follow. This iatrogenic injury can impair normal diaphragmatic function contributing to difficulties in weaning from MV while simultaneously increasing patients’ morbidity and mortality. A TTDN device that elicits diaphragm contractions has previously been shown to mitigate atrophy during MV in a preclinical model. Preliminary results previously published have shown its specific fiber-type effects; however, how it compares to NV-NP is unknown.
      METHODS: This study used a semi-randomized mock ICU model where 12 pigs (50-60kg) were assigned to one of two ventilation conditions for 50 hours: MV-Only and MV+TTDN. Additionally, six pigs (50-60kg) were assigned to an NV-NP group. Diaphragm biopsies were fiber-typed by immunohistochemistry with their CSA measured using ImageJ. The measured CSAs were normalized to each pig’s weight for comparability between ventilation conditions.
      RESULTS: MV-Only pigs showed the largest degree of atrophy, with mean CSA differences of 33%, 41%, 46%, and 64% from NV-NP pigs, for type I, IIA, IIX, and all myofibers respectively. MV+TTDN pigs showed less atrophy than MV-Only pigs, with mean CSA differences of 6%, 27%, 24%, and 22% from NV-NP pigs, for type I, II, IIX, and all myofibers respectively. The normalized CSAs for each myofiber type between all three ventilation conditions were significantly different, with p<0.001.
      CONCLUSIONS: TTDN therapy mitigates atrophy from VIDD for all diaphragm myofiber subclasses
      CLINICAL IMPLICATIONS: This will likely be clinically important as this allows for the full functional repertoire of all myofiber subclasses to ensure effective and successful liberation from MV.
      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