Mechanical ventilation aggravates transfusion-related acute lung injury induced by MHC-I class antibodies.
OBJECTIVE
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 may be a risk factor for developing TRALI. We examined the influence of mechanical ventilation (MV) on the development of TRALI, combining a murine MV model causing ventilator-induced lung injury with a model of antibody-induced TRALl.


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


RESULTS
All animals receiving MHC-I antibodies developed TRALI within 2 h. 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 to unventilated controls. The use of high tidal volume ventilation resulted in a further increase in protein leakage and pulmonary edema.


CONCLUSIONS
Mechanical ventilation (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.
Vlaar
A P J
AP
Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands. a.p.vlaar@amc.uva.nl
Wolthuis
E K
EK
Hofstra
J J
JJ
Roelofs
J J T H
JJ
Boon
L
L
Schultz
M J
MJ
Lutter
R
R
Juffermans
N P
NP
D055371:Acute Lung Injury / Q000209:etiology* / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016638:Critical Illness; D004195:Disease Models, Animal; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology*; D012307:Risk Factors; D065227:Transfusion Reaction; D055397:Ventilator-Induced Lung Injury / Q000276:immunology*; D012122:Ventilators, Mechanical / Q000009:adverse effects*
D000906:Antibodies; D000949:Histocompatibility Antigens Class II