Dexamethasone treatment attenuates early seawater instillation-induced acute lung injury in rabbits
Introduction
The World Health Organization (WHO) estimates the annual worldwide incidence of death by drowning to be about 400,000. Furthermore, drowning is a leading cause of accidental death in children [1]. Current data suggest that hypoxemia is the major pathophysiologic abnormality after drowning. In 85–90% cases, the hypoxemia is related to aspiration. Water aspiration can induce acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), which are characterized by an acute inflammatory process in airspaces and lung parenchyma. These syndromes are manifestations of the loss of barrier function of the alveolar epithelial and pulmonary capillary endothelial cells [2]. Administration of corticoids is a drug option in the therapy of ALI/ARDS, according to present pathophysiological concepts. However, definitive evidence to support their use is lacking [3]. There is also very little evidence on the value of giving corticoids in cases of seawater drowning induced ALI/ARDS [4].
Therefore, there were three objectives to investigate in this study using a rabbit model of intratracheal instillation of seawater-induced ALI. The first objective was to determine whether dexamethasone would improve gas exchange and the total thoracic compliance. The second objective was to study whether dexamethasone would relieve the injury of lung endothelial cell and alveolar epithelial cell and the airspace inflammation. In addition, clinical data have demonstrated that the presence of maximal alveolar fluid clearance (AFC) is associated with improved mortality in patients with ALI and ARDS [5], [6]. The current working model of the lung fluid balance indicates that Na+ enters alveolar epithelial cells at apical surface via predominantly epithelial Na+ channels (ENaC) and is pumped out by basolateral Na+/K+-adenosine triphosphatase (Na+/K+-ATPase), which produces a unidirectional Na+ transport and resulting fluid absorption from the alveolar space [7]. Thus, the final objective was to examine whether dexamethasone would decrease extravascular lung water (ELW) and up-regulate the expression of ENaC and Na+/K+-ATPase in lung tissue.
Section snippets
Animal preparation
All animal experiments were undertaken with protocols approved by the Naval General Hospital of PLA, Committee on Animal Research. Thirty healthy male New Zealand white rabbits weighing 2.35 ± 0.36 kg, range 2.1–2.6 kg (Keyu animal feeding center, Beijing, China, Certificate Number: SCXK-jing-2002-0005) were randomly allocated to three groups: control group (CG), dexamethasone treatment group (DG) and normal group (NG).
Experimental protocols
CG (n = 12): The rabbits were anesthetized with 20% urethane (1.0 g/kg) injected
Effect of dexamethasone treatment on PaO2, Cst and Cdyn
As shown in Fig. 1, seawater instillation caused a marked decrease in the PaO2 (Fig. 1A), Cst (Fig. 1B) and Cdyn (Fig. 1C), which could be partly improved by dexamethasone treatment. At 180 min post seawater instillation, the DG's PaO2 was 253 ± 77 mmHg, which was significantly higher than the CG's (149 ± 68 mmHg) (p < 0.01, Fig. 1A). At the same point, the DG's Cst (1.52 ± 0.16 ml/cmH2O) or Cdyn (1.13 ± 0.15 ml/cmH2O) was also significantly higher than the CG's Cst (0.97 ± 0.11 ml/cmH2O) or Cdyn (0.85 ± 0.13 ml/cmH
Discussion
Current evidence indicates that short-duration, high-dose corticosteroids therapy is not effective for early ARDS or severe sepsis. But the cause of ARDS is complex, this result is not suitable for all subgroups with ARDS. An evidence review of corticosteroids for ARDS found that certain subgroups with early ALI/ARDS do benefit from corticosteroids. There are (1) Level I evidence that high-dose corticosteroids benefit patients suffering P. carinii pneumonia and (2) Level II evidence that
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Seawater induces apoptosis in alveolar epithelial cells via the Fas/FasL-mediated pathway
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Both these authors contributed equally to this work.