Increased susceptibility to ventilator-associated lung injury persists after clinical recovery from experimental endotoxemia.
BACKGROUND
Endotoxin, when delivered shortly before or during mechanical ventilation, increases susceptibility to ventilation-associated lung injury. However, it is unclear whether increased susceptibility to ventilator-associated lung injury is still present after clinical recovery from a transient endotoxin challenge.


METHODS
Anesthetized rats were submitted to a 4-h period of mechanical ventilation with low (8 ml/kg) or high (24, 27, or 30 ml/kg) tidal volumes (VTs) 24 h after transient illness had been provoked by a single nonlethal intravenous injection of Escherichia coli endotoxin. Control animals were injected with phosphate-buffered saline and underwent the same protocol.


RESULTS
At 24 h, endotoxin-treated nonventilated animals showed no symptoms of clinical illness, and oxygenation was comparable with that of controls, but lung neutrophil counts were increased. Compared with controls, mechanical ventilation with high VT induced a stronger pulmonary inflammatory response and more severe lung injury in endotoxin-treated animals, as indicated by impaired oxygenation, increased lung wet-to-dry weight ratio, and increased levels of protein, neutrophils, and cytokines in lung lavage fluid. In addition, the highest VT resulted in increased mortality in endotoxin-treated animals. Low VT after endotoxin treatment did not cause functional pulmonary impairment but induced an inflammatory response.


CONCLUSIONS
In this animal model, a 24-h delay after a single systemic injection of endotoxin resulted in clinical recovery and preserved pulmonary function but did not prevent increased susceptibility to ventilator-associated lung injury provoked by high VT. Residual pulmonary inflammation and neutrophilic infiltration at initiation of mechanical ventilation probably contribute to these findings.
Schreiber
Torsten
T
Department of Anesthesiology and Intensive Care Medicine, Friedrich-Schiller-Universitaet, Jena, Germany. torsten.schreiber@med.uni-jena.de
Hueter
Lars
L
Schwarzkopf
Konrad
K
Hohlstein
Sylvia
S
Schmidt
Barbara
B
Karzai
Waheedullah
W
D000818:Animals; D018893:Bronchoalveolar Lavage; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D007249:Inflammation / Q000473:pathology; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D055370:Lung Injury; D008297:Male; D009929:Organ Size / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial / Q000009:adverse effects*; D012129:Respiratory Function Tests; D013534:Survival; D013990:Tidal Volume / Q000187:drug effects / Q000502:physiology; D012122:Ventilators, Mechanical / Q000009:adverse effects*
D016207:Cytokines; D011506:Proteins