Abstract
BackgroundFat embolism syndrome (FES) associated with acute lung injury (ALI) is a clinical condition following long bone fracture. We have reported 14 victims due to ALI with FES. Our laboratory has developed an animal model that produced fat emboli (FE). The major purpose of this study was to test whether neutrophil activation with phorbol myristate acetate (PMA) and inhibition with sivelestat (SVT) exert protection on the lung.MethodsThe lungs of Sprague-Dawley rats were isolated and perfused. FE was produced by addition of corn oil micelles into the lung perfusate. PMA and SVT were given simultaneously with FE. Parameters such as lung weight/body weight ratio, LW gain, exhaled nitric oxide (NO), protein concentration in bronchoalveolar lavage relating to ALI were measured. The neutrophil elastase (NE), myeloperoxidase, malondialdehyde and phopholipase A2 activity were determined. We also measured the nitrate/nitrite, methyl guanidine (MG), and cytokines. Pulmonary arterial pressure and microvascular permeability were assessed. Lung pathology was examined and scored. The inducible and endothelial NO synthase (iNOS and eNOS) were detected.ResultsFE caused ALI and increased biochemical factors. The challenge also resulted in pulmonary hypertension and increased microvascular permeability. The NE appeared to be the first to reach its peak at 1 hr, followed by other factors. Coadministration with PMA exacerbated the FE-induced changes, while SVT attenuated the effects of FE.ConclusionsThe FE-induced lung changes were enhanced by PMA, while SVT had the opposite effect. Sivelestat, a neutrophil inhibitor may be a therapeutic choice for patients with acute respiratory distress syndrome (ARDS) following fat embolism.
Highlights
Fat embolism syndrome (FES) associated with acute lung injury (ALI) is a clinical condition following long bone fracture
In order to elucidate the possible mediators involved in the acute respiratory distress syndrome (ARDS) associated with FES, we have developed an animal model that produces fat embolism in anesthetized rats
We have reported that pretreatment of inducible nitric oxide synthase (iNOS) isoform inhibitors attenuated the inflammatory responses to endotoxin, fat embolism and phorbol myristate acetate (PMA)
Summary
Fat embolism syndrome (FES) associated with acute lung injury (ALI) is a clinical condition following long bone fracture. Our laboratory has developed an animal model that produced fat emboli (FE). Fat embolism syndrome (FES) is a serious clinical problem in patients associated with long bone fracture [1,2,3]. We have reported a total of 14 cases who died of acute respiratory distress syndrome (ARDS) associated with FES [1,3]. In order to elucidate the possible mediators involved in the ARDS associated with FES, we have developed an animal model that produces fat embolism in anesthetized rats. The animal model has been used to study the protective effect of N-Acetylcysteine [6], and the effects of inducible nitric oxide synthase (iNOS) inhibitors and nitric oxide donors [7]. Our results indicate that N-acetylcysteine provides protection to the FES, while nitric oxide is detrimental
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