Intra-operative hemi-diaphragm electrical stimulation does not change mitochondrial function in cardiothoracic surgery patients

Background: Mechanical ventilation during cardiothoracic surgery is life-saving, but leads to ventilator-induced diaphragm dysfunction (VIDD) and prolongs weaning from the ventilator and hospital stay. Intra-operative diaphragm electrical stimulation may preserve mitochondrial function, and thus prevent VIDD. Methods We studied 21 patients stimulating a phrenic nerve of one hemidiaphragm every 30 min for 1min during a surgery. We collected diaphragm biopsies after the last stimulation and analyzed for mitochondrial respiration in permeabilized fibers, and protein expression and enzymatic activity of biomarkers of muscle atrophy, oxidative stress and mitophagy. Results Patients received on average 6.2 (1.9) stimulation bouts. Stimulated hemidiaphragm showed attenuated integrative and intrinsic mitochondrial respiratory function. There were no significant differences between oxidative stress, mitophagy and atrophy protein expression levels, and mitochondrial enzyme activities. Conclusions Intraoperative phrenic nerve electrical stimulation led to an impairment of mitochondrial respiration in the stimulated hemidiaphragm without differences in biomarkers of atrophy and oxidative stress. Future studies warrant investigating optimal stimulation doses and testing post-operative chronic stimulation effects on weaning from the ventilator and rehabilitation outcomes. Trial registration: NCT03303040, Registered on the 5th of October 2017. No retrospective registration statement needed – first subject was enrolled on 2/14/2018.