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 hours post-injury with volume-control at 8 ml/kg, PEEP 5 cmH 2 O, respiratory rate and FiO 2 set to achieve normal arterial blood gases. Two groups received TTDN: every second breath (MV+TTDN50%, n=6) or every breath (MV+TTDN100%, n=6). One group received ventilation only (MV, n=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 ELISA and compared to serum samples. Percentage of abnormal diaphragm tissue was different between MV (8.1% (6.0-8.8)) vs. MV+TTDN50% (3.4% (2.1-4.8)), p=0.010 and MV vs. MV+TTDN100% (3.1% (2.5-4.0)), p=0.005. Percentage of abnormal quadriceps tissue was not different between groups. Cytokine concentration patterns in diaphragm samples were different between all groups (p<0.001) and the interaction between TTDN application and resultant cytokine concentration pattern was significant (p=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.