Pulmonary atelectasis during low stretch ventilation: "open lung" versus "lung rest" strategy.
OBJECTIVE
Limiting tidal volume (VT) may minimize ventilator-induced lung injury (VILI). However, atelectasis induced by low VT ventilation may cause ultrastructural evidence of cell disruption. Apoptosis seems to be involved as protective mechanisms from VILI through the involvement of mitogen-activated protein kinases (MAPKs). We examined the hypothesis that atelectasis may influence the response to protective ventilation through MAPKs.


METHODS
Prospective randomized study.


METHODS
University animal laboratory.


METHODS
Adult male 129/Sv mice.


METHODS
Isolated, nonperfused lungs were randomized to VILI: VT of 20 mL/kg and positive end-expiratory pressure (PEEP) zero; low stretch/lung rest: VT of 6 mL/kg and 8-10 cm H2O of PEEP; low stretch/open lung: VT of 6 mL/kg, two recruitment maneuvers and 14-16 cm H2O of PEEP. Ventilator settings were adjusted using the stress index.


RESULTS
Both low stretch strategies equally blunted the VILI-induced derangement of respiratory mechanics (static volume-pressure curve), lung histology (hematoxylin and eosin), and inflammatory mediators (interleukin-6, macrophage inflammatory protein-2 [enzyme-linked immunosorbent assay], and inhibitor of nuclear factor-kB[Western blot]). VILI caused nuclear swelling and membrane disruption of pulmonary cells (electron microscopy). Few pulmonary cells with chromatin condensation and fragmentation were seen during both low stretch strategies. However, although cell thickness during low stretch/open lung was uniform, low stretch/lung rest demonstrated thickening of epithelial cells and plasma membrane bleb formation. Compared with the low stretch/open lung, low stretch/lung rest caused a significant decrease in apoptotic cells (terminal deoxynucleotidyl transferase mediated deoxyuridine-triphosphatase nick end-labeling) and tissue expression of caspase-3 (Western blot). Both low stretch strategies attenuated the activation of MAPKs. Such reduction was larger during low stretch/open lung than during low stretch/lung rest (p < 0.001).


CONCLUSIONS
Low stretch strategies provide similar attenuation of VILI. However, low stretch/lung rest strategy is associated to less apoptosis and more ultrastructural evidence of cell damage possibly through MAPKs-mediated pathway.
Fanelli
Vito
V
Dipartimento di Anestesiologia e Rianimazione, Università di Torino, Ospedale S Giovanni Battista-Molinette, Torino, Italy.
Mascia
Luciana
L
Puntorieri
Valeria
V
Assenzio
Barbara
B
Elia
Vincenzo
V
Fornaro
Giancarlo
G
Martin
Erica L
EL
Bosco
Martino
M
Delsedime
Luisa
L
Fiore
Tommaso
T
Grasso
Salvatore
S
Ranieri
V Marco
VM
D000818:Animals; D020930:MAP Kinase Kinase Kinases / Q000502:physiology*; D051379:Mice; D001261:Pulmonary Atelectasis / Q000209:etiology* / Q000276:immunology; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000379:methods*; D055397:Ventilator-Induced Lung Injury / Q000209:etiology* / Q000276:immunology
D020930:MAP Kinase Kinase Kinases