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Mechanical ventilation aggravates transfusion-related acute lung injury induced by MHC class I antibodies


Transfusion-related acute lung injury (TRALI) occurs more often in critically ill patients than in a general hospital population, possibly due to the presence of underlying inflammatory conditions that may prime pulmonary neutrophils. Mechanical ventilation (MV) may be a risk factor for developing TRALI. We determined the influence of MV on the development of TRALI, combining a murine MV model causing ventilator-induced lung injury with a model of antibody-induced TRALI [1, 2].


BALB/c mice (n = 84) were ventilated for 5 hours with low (7.5 ml/kg) or high (15 ml/kg) tidal volume, a positive end-expiratory pressure of 2 cmH2O and a fraction of inspired oxygen of 50%. After 3 hours of MV, TRALI was induced by infusion of MHC-I antibodies (4.5 mg/kg), controls received vehicle. Nonventilated animals receiving vehicle, isotype or MHC-I antibodies served as additional controls.


All animals receiving MHC-I antibodies developed TRALI within 2 hours. In mice in which TRALI was induced, MV with low tidal volumes aggravated pulmonary injury as evidenced by an increase in neutrophil influx, pulmonary and systemic levels of cytokines and lung histopathological changes compared with unventilated controls. The use of high tidal volume ventilation resulted in a further increase in protein leakage and pulmonary edema.


MV synergistically augmented lung injury during TRALI, which was even further enhanced by the use of injurious ventilator settings. Results suggest that MV may be a risk factor for the onset of TRALI and may aggravate the course of disease.


  1. Wolthuis EK, Vlaar AP, Choi G, et al: Mechanical ventilation using noninjurious ventilation settings causes lung injury in the absence of preexisting lung injury in healthy mice. Crit Care. 2009, 13: R1-10.1186/cc7688.

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  2. Looney MR, Su X, Van Ziffle JA, et al: Neutrophils and their Fcγ receptors are essential in a mouse model of transfusion-related acute lung injury. J Clin Invest. 2006, 116: 1615-1623. 10.1172/JCI27238.

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Vlaar, A., Wolthuis, E., Hofstra, J. et al. Mechanical ventilation aggravates transfusion-related acute lung injury induced by MHC class I antibodies. Crit Care 14 (Suppl 1), P192 (2010).

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