0854. Metabolomic changes by mass spectrometry in lung tissue from septic rats with mechanical ventilation-induced lung injury

Objective

To identify metabolomic changes in lung tissue associated with lung injury induced by mechanical ventilation (VILI) in animals with sepsis, using for the first time a global unbiased metabolomic fingerprinting approach.

Methods

Rats received cecal-ligation and puncture (CLP) or sham operation, and 24 h later underwent mechanical ventilation for 2.5 h with either V_T=9 ml/kg, positive end-expiratory pressure (PEEP)=0 cm H₂O (n=9 and n=12, without and with CLP, respectively); or V_T=25 ml/kg, PEEP=5 cm H₂O (n=13 and n=12, without and with CLP, respectively). Lung tissue samples were obtained and analyzed by nontargeted global fingerprinting approach for lung tissue analysis, applying multiple complementary analytical techniques, including liquid cromatography-mass spectrometry (MS), gas cromatography-MS, and capillary electrophoresis-MS. We followed the Principles of Laboratory Animal Care (2010/63/UE 22-09, RD 53/2013 BOE 1-02, ley 32/2007 BOE 7-11).

Results

Metabolomic changes characteristic of sepsis and VILI were identified. Lung tissue samples from septic rats with VILI were characterized by a specific metabolomic profile as compared to samples from septic rats without VILI. Metabolomic changes indicated increased oxidative stress, and changes in purine, energy, carnitine, aminoacid, urea cycle, vitamines, collagen, ceramide-sphingomyelin and phospholipid metabolism.

Conclusion

A particular metabolomic profile can be identified in lung tissue from septic rats with lung injury induced by mechanical ventilation.