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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.