Transvenous stimulation yields exposure-dependent protection from ventilator-induced diaphragm atrophy

Mechanical ventilation (MV)-induced diaphragmatic atrophy can contribute to weaning difficulties. A temporary transvenous diaphragm neurostimulation (TTDN) device that elicits diaphragm contractions has previously been shown to mitigate atrophy during MV in a preclinical model; however, its effects on different myofiber types remain unknown. It is important to examine these effects, as each myofiber type plays a role in the range of diaphragmatic movements to ensure successful liberation from MV. Eighteen pigs were assigned to one of three ventilation conditions for 50 hours: MV-Only and TTDN contracting the diaphragm every other breath or every breath synchronously with MV (TTDN50% + MV and TTDN100% + MV, respectively). Six pigs were assigned to a never-ventilated, never-paced (NV-NP) group. Diaphragm biopsies were fiber-typed, and myofiber cross-sectional areas were measured and normalized to subject weight. There were effect differences based on TTDN exposure. The TTDN100% + MV group showed less atrophy in Type 2A and 2X myofibers than the TTDN50% + MV group, relative to the NV-NP group. The TTDN50% + MV animals showed less MV-induced atrophy in type 1 myofibers than TTDN100% + MV animals. Additionally, there were no significant differences in proportions of myofiber types between each condition. TTDN applied synchronously with MV for 50 hours mitigates MV-induced atrophy in all myofiber types, with no evidence of stimulation-induced myofiber-type shift. At this stimulation profile, enhanced protection for type 1 myofibers and type 2 myofibers was seen when diaphragm contractions occurred every other breath and every breath, respectively.NEW & NOTEWORTHY This research adds to our current understanding of applying temporary transvenous diaphragmatic neurostimulation (TTDN) synchronously with mechanical ventilation by examining its diaphragm-myofiber effects. We observed that using this therapy for 50 hours with mechanical ventilation not only mitigated ventilator-induced atrophy on all myofiber types with dose effects, it also did not invoke alterations in diaphragm myofiber type proportions. These findings suggest that applying TTDN with mechanical ventilation at different doses represents its broad spectrum use and viability as a diaphragm protective strategy.