Transvenous phrenic nerve stimulation reduces diaphragm injury during controlled mechanical ventilation in a preclinical model of ARDS

Patients with acute respiratory distress syndrome (ARDS) require periods of deep sedation and mechanical ventilation, leading to diaphragm dysfunction. Our study seeks to determine whether the combination of temporary transvenous diaphragm neurostimulation (TTDN) and mechanical ventilation changes the degree of diaphragm injury and cytokines concentration in a preclinical ARDS model. Moderate ARDS was induced in pigs using oleic acid, followed by ventilation for 12 h post-injury with volume-control at 8 mL/kg, positive end-expiratory pressure (PEEP) 5 cmH₂O, respiratory rate and [Formula: see text] set to achieve normal arterial blood gases. Two groups received TTDN: every second breath (MV + TTDN50%, <i>n</i> = 6) or every breath (MV + TTDN100%, <i>n</i> = 6). One group received ventilation only (MV, <i>n</i> = 6). Full-thickness diaphragm and quadricep muscle biopsies were taken at study end. Samples were fixed and stained with hematoxylin and eosin and a point-counting technique was applied to calculate abnormal muscle area fraction. Cytokine concentrations were measured in homogenized tissue using porcine-specific enzyme-linked immunosorbent assay (ELISA) and compared with serum samples. Percentage of abnormal diaphragm tissue was different between MV [8.1% (6.0-8.8)] versus MV + TTDN50% [3.4% (2.1-4.8)], <i>P</i> = 0.010 and MV versus MV + TTDN100% [3.1% (2.5-4.0)], <i>P</i> = 0.005. Percentage of abnormal quadriceps tissue was not different between groups. Cytokine concentration patterns in diaphragm samples were different between all groups (<i>P</i> < 0.001) and the interaction between TTDN application and resultant cytokine concentration pattern was significant (<i>P</i> = 0.025). TTDN, delivered in synchrony with mechanical ventilation, mitigated diaphragm injury, as evidenced by less abnormal tissue in the diaphragm samples, in pigs with oleic acid-induced ARDS and is an exciting tool for lung and diaphragm-protective ventilation.<b>NEW & NOTEWORTHY</b> This study adds to our understanding of applying transvenous diaphragm neurostimulation synchronously with mechanical ventilation by examining its effects on diaphragm muscle injury and cytokine concentration patterns in pigs with acute respiratory distress syndrome (ARDS). We observed that using this therapy for 12 h post lung injury mitigated ventilator-induced diaphragm injury and changed the pattern of cytokine concentration measured in diaphragm tissue. These findings suggest that transvenous diaphragm neurostimulation is an exciting tool for lung and diaphragm protective ventilation.