scholarly journals Open Tracheostomy Gastric Acid Aspiration Murine Model of Acute Lung Injury Results in Maximal Acute Nonlethal Lung Injury

Author(s):  
Ravi Alluri ◽  
Hilliard L. Kutscher ◽  
Barbara A. Mullan ◽  
Bruce A. Davidson ◽  
Paul R. Knight
2012 ◽  
Vol 117 (6) ◽  
pp. 1322-1334 ◽  
Author(s):  
Aline M. Ambrosio ◽  
Rubin Luo ◽  
Denise T. Fantoni ◽  
Claudia Gutierres ◽  
Qin Lu ◽  
...  

Background In acute lung injury positive end-expiratory pressure (PEEP) and recruitment maneuver are proposed to optimize arterial oxygenation. The aim of the study was to evaluate the impact of such a strategy on lung histological inflammation and hyperinflation in pigs with acid aspiration-induced lung injury. Methods Forty-seven pigs were randomly allocated in seven groups: (1) controls spontaneously breathing; (2) without lung injury, PEEP 5 cm H2O; (3) without lung injury, PEEP titration; (4) without lung injury, PEEP titration + recruitment maneuver; (5) with lung injury, PEEP 5 cm H2O; (6) with lung injury, PEEP titration; and (7) with lung injury, PEEP titration + recruitment maneuver. Acute lung injury was induced by intratracheal instillation of hydrochloric acid. PEEP titration was performed by incremental and decremental PEEP from 5 to 20 cm H2O for optimizing arterial oxygenation. Three recruitment maneuvers (pressure of 40 cm H2O maintained for 20 s) were applied to the assigned groups at each PEEP level. Proportion of lung inflammation, hemorrhage, edema, and alveolar wall disruption were recorded on each histological field. Mean alveolar area was measured in the aerated lung regions. Results Acid aspiration increased mean alveolar area and produced alveolar wall disruption, lung edema, alveolar hemorrhage, and lung inflammation. PEEP titration significantly improved arterial oxygenation but simultaneously increased lung inflammation in juxta-diaphragmatic lung regions. Recruitment maneuver during PEEP titration did not induce additional increase in lung inflammation and alveolar hyperinflation. Conclusion In a porcine model of acid aspiration-induced lung injury, PEEP titration aimed at optimizing arterial oxygenation, substantially increased lung inflammation. Recruitment maneuvers further improved arterial oxygenation without additional effects on inflammation and hyperinflation.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Liang Cui ◽  
Dahai Zheng ◽  
Yie Hou Lee ◽  
Tze Khee Chan ◽  
Yadunanda Kumar ◽  
...  

2016 ◽  
Vol 9 (4) ◽  
pp. 332-338
Author(s):  
Tae Young Jang ◽  
Ah-Yeoun Jung ◽  
Young Hyo Kim

2017 ◽  
Vol 47 ◽  
pp. 218-226 ◽  
Author(s):  
Ahmed Nadeem ◽  
Nahid Siddiqui ◽  
Naif O. Al-Harbi ◽  
Sabry M. Attia ◽  
Shakir D. AlSharari ◽  
...  

2014 ◽  
Vol 10 (1) ◽  
pp. 447-452 ◽  
Author(s):  
XIAN WANG ◽  
LEI ZHANG ◽  
WEI DUAN ◽  
BIN LIU ◽  
PING GONG ◽  
...  

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
James G. Macfarlane ◽  
David A. Dorward ◽  
Marie-Hélène Ruchaud-Sparagano ◽  
Jonathan Scott ◽  
Christopher D. Lucas ◽  
...  

Abstract Background Neutrophils rapidly respond to and clear infection from tissues, but can also induce tissue damage through excessive degranulation, when acute inflammation proceeds unchecked. A number of key neutrophil functions, including adhesion-dependent degranulation, are controlled by src family kinases. Dasatinib is a potent src inhibitor used in treating patients with chronic myeloid leukaemia and treatment-resistant acute lymphoblastic leukaemia. We hypothesized that dasatinib would attenuate acute inflammation by inhibiting neutrophil recruitment, degranulation and endothelial cell injury, without impairing bacterial clearance, in a murine model of bacteria-induced acute lung injury. C57BL/6 mice received intratracheal Escherichia coli, and were treated with intraperitoneal dasatinib or control. Bacterial clearance, lung injury, and markers of neutrophil recruitment and degranulation were measured. Separately, human blood neutrophils were exposed to dasatinib or control, and the effects on a range of neutrophil functions assessed. Results Dasatinib was associated with a dose-dependent significant increase in E. coli in the mouse lung, accompanied by impairment of organ function, reflected in significantly increased protein leak across the alveolar-capillary membrane. However, the number of neutrophils entering the lung was unaffected, suggesting that dasatinib impairs neutrophil function independent of migration. Dasatinib did not cause direct toxicity to human neutrophils, but led to significant reductions in phagocytosis of E. coli, adhesion, chemotaxis, generation of superoxide anion and degranulation of primary and secondary granules. However, no biologically important effect of dasatinib on neutrophil degranulation was observed in mice. Conclusions Contrary to our starting hypothesis, src kinase inhibition with dasatinib had a detrimental effect on bacterial clearance in the mouse lung and therefore does not represent an attractive therapeutic strategy to treat primary infective lung inflammation. Data from human neutrophils suggest that dasatanib has inhibitory effects on a range of neutrophil functions.


Author(s):  
F Fichtner ◽  
MT Voelker ◽  
A Hoelman ◽  
T Busch ◽  
M Kasper ◽  
...  

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