Impact of Reverse Triggering Dyssynchrony during Lung-Protective Ventilation on Diaphragm Function: An Experimental Model

<b>Rationale:</b> Reverse triggering dyssynchrony (RT) is a patient-ventilator interaction where a respiratory muscle contraction is triggered by a passive mechanical insufflation. Its impact on diaphragm structure and function is unknown. <b>Objectives:</b> To establish an animal model of RT with lung injury receiving lung-protective ventilation and to assess its impact on the structure and function of the diaphragm. <b>Methods:</b> Lung injury was induced by surfactant depletion and high-stress ventilation in 32 ventilated pigs. Animals were allocated to receive passive mechanical ventilation (Vt: 10 ml/kg; respiratory rate [RR]: 30-35 breaths/min; <i>n</i> = 8) or a more lung-protective strategy (Vt: 6-8 ml/kg; <i>n</i> = 24) with adjustments in RR to facilitate the occurrence of RT for 3 hours. Diaphragm function (transdiaphragmatic pressure [Pdi] during phrenic nerve stimulation [force/frequency curve]) and structure (biopsies) were assessed. The impact of RT on diaphragm function was analyzed according to the breathing effort assessed by the pressure-time product. <b>Measurements and Main Results:</b> Compared with passive ventilation, the protective ventilation group with RT received significantly lower Vt (7 vs. 10 ml/kg) and higher RR (45 vs. 31 breaths/min). An entrainment pattern of 1:1 was the most frequently occurring in 83% of the animals. Breathing effort induced by RT was highly variable across animals. RT with the lowest tercile of breathing effort was associated with 23% higher twitch Pdi compared with passive ventilation, whereas RT with high breathing effort was associated with a 10% lower twitch Pdi and a higher proportion of abnormal muscle fibers. <b>Conclusions:</b> In a reproducible animal model of RT with variable levels of breathing effort and entrainment patterns, RT with high effort is associated with impaired diaphragm function, whereas RT with low effort is associated with preserved diaphragm force.