in the current issue of critical care , de prost and colleagues   evaluated the impact of protective and injurious ventilation strategies on lung neutrophil distribution and activation in sheep 2 hours after endotoxin infusion .
the protective ventilation strategy consisted of 8 ml / kg tidal volume and titration of positive end - expiratory pressure ( peep ) to achieve a plateau pressure of 30 cm h2o .
peep was not applied in the injurious ventilation protocol , and tidal volumes of 14 to 18 ml / kg were delivered .
positron emission tomography ( pet ) imaging and n-[nitrogen]-saline infusion were performed to evaluate regional lung perfusion and shunt fraction .
cellular metabolic activities were measured by using an f - fluorodeoxyglucose ( f - fdg ) infusion protocol , and lung leukocyte infiltration was determined by histological analysis .
their results show that protective ventilation was associated with better gas exchange and lower shunt fraction in dependent lung regions prior to endotoxin infusion .
endotoxin infusion worsened gas exchange in both groups , but less so in sheep receiving protective ventilation .
protective ventilation also attenuated f - fdg uptake and phosphorylation after endotoxin infusion , particularly in dependent areas of the lungs .
the authors conclude that a protective ventilation strategy that optimizes alveolar recruitment and minimizes alveolar distension may mitigate neutrophil activation in the lung , particularly in dependent areas , during early experimental acute lung injury ( ali ) .
use of the sheep model in this study had several advantages . with a size comparable to that of the human , the ovine model allowed an analysis of physiological endpoints that are clinically relevant and permitted the application of ventilation strategies that are similar to those used in clinical practice .
the tidal volumes and peep applied in the protective strategy are similar to those advocated for use in the clinical setting .
alternatively , a study by takeuchi and colleagues   described a method of pressure - volume curve analysis to identify the most appropriate peep during mechanical ventilation in an adult sheep model of ali , which may further optimize lung protection and would be interesting to apply in the model used by de prost and colleagues .
the endotoxin infusion model has the advantage of being reproducible and easily titrated and is known to induce neutrophil accumulation in the lungs .
however , the protocol appears to have induced minimal histological evidence of lung injury as indicated by lung injury scores of 0 to 1 ( on a scale of 0 to 4 ) in both groups .
given the lack of demonstrable lung injury at the histological level , it is possible that differences in normal lung recruitment and hemodynamics contributed to the dissimilarities in gas exchange and shunt fraction observed between groups .
however , changes in alveolar - capillary integrity that were not detectable by light microscopy may also be present early after endotoxin infusion and could have contributed to the observed gas exchange perturbations .
evidence indicates that dysregulated inflammation and the inappropriate accumulation and activation of leukocytes , especially neutrophils , contribute to the pathogenesis of ali .
furthermore , investigators have postulated that protective ventilation strategies decrease regional lung inflammation in subjects with ali .
the assessment of cellular metabolic activity by using pet imaging and f - fdg infusion along with the evaluation of lung perfusion and ventilation , as performed by de prost and colleagues , is an informative , non - invasive approach that provides useful data regarding regional differences in cellular metabolic rate .
the technique may have practical utility since studies have shown that evaluation of f - fdg uptake may be valuable in predicting respiratory failure and evaluating therapy in clinical and experimental models of ali [ 8 - 10 ] .
the present study extends previous reports by documenting the impact of ventilation strategies on regional metabolic activity and neutrophil accumulation early during the course of ali .
although differences in cellular metabolic activity were observed between groups , neutrophil accumulation in the lungs was not different when sheep receiving protective or injurious ventilation were compared .
the authors interpret that finding as possibly being indicative of increased neutrophil activation in sheep receiving injurious ventilation .
that conclusion is based , in part , on previous studies that showed neutrophil activation to be the primary factor contributing to increased f - fdg uptake and phosphorylation during ali . however , as noted by the authors , it is unclear whether the alterations in f - fdg uptake and phosphorylation observed in their analysis are entirely specific for neutrophils .
it is possible that the metabolic rates of other leukocyte and non - leukocyte cell populations were affected .
evidence indicates that alterations in macrophage , epithelial , and endothelial cell functions occur during ali .
further studies are needed to identify the cell populations that are affected and the functional importance of the observed alterations .
overall , the study by de prost and colleagues provides new insights into the impact of ventilation strategies on regional cellular metabolic activity during early ali .
more investigation is needed to extrapolate their findings into the clinical setting and determine the functional importance of their findings .
it is hoped that the group will perform follow - up studies to determine whether the observed changes in regional leukocyte activation are predictive of progressive respiratory failure and pulmonary injury as well as better define the specific cell populations involved .
18f - fdg : f - fluorodeoxyglucose ; ali : acute lung injury ; peep : positive end - expiratory pressure ; pet : positron emission tomography .
 protective mechanical ventilation is currently accepted as a key strategy for the management of acute lung injury ( ali ) and its most severe form , acute respiratory distress syndrome . 
 the study by de prost and colleagues in the current issue of critical care provides new insights into the impact of ventilation strategies on pulmonary function , gas exchange , and regional cellular metabolic activity during early ali in sheep . 
 the group reports that a protective ventilation strategy may attenuate neutrophil activation in dependent lung regions during early experimental ali . 
 this is an innovative report that provides the basis for further study . 