Gene expression profiles in respiratory settings in rats under extracorporeal membrane oxygenation

Venovenous extracorporeal membrane oxygenation (VV-ECMO) is an effective lung protection strategy that avoids ventilator-induced lung injury. However, appropriate respiratory settings for VV-ECMO are yet to be established. This study aimed to elucidate the effects of ventilation under VV-ECMO using a newly developed rat VV-ECMO model and analyzed gene expression profiles.

Rats were assigned to three groups of five rats each: spontaneous breathing, conventional-protective ventilation, and ultra-protective ventilation. The conventional protective and ultraprotective ventilation groups received volume-controlled ventilation at a frequency of 60 and 20 beats/min, with tidal volumes of 6 and 3 mL/kg, respectively. VV-ECMO was performed at a pump flow rate of 20-30 mL/kg/min. At 120 min post initiation of VV-ECMO, rats were euthanized, and their lungs were harvested. Changes in gene expression were assessed using microarray analysis.

Gene expression profile analyses revealed lowest expression of inflammation/immune promotion, cytotoxicity, and cell proliferation related genes (Defa5, Prg2, Siglec8, Atf3, Rnd1, Ctsg, and Gc), and the highest expression of inflammation/immune suppression related genes (Pp2d1) in the spontaneous breathing group as compared to that in the other two mechanical ventilation groups.

The findings of this study demonstrated that spontaneous breathing was the least invasive respiratory setting under VV-ECMO. Further, mechanical ventilation may be associated with lung injury even at low ventilation frequency and tidal volume.