BACKGROUND: Pulmonary fat embolism (FE) in patients after major bone fracture and other trauma may lead to acute respiratory distress, but few clinical evidence of lung injury remains, and there is a dearth of histopathologic information after the initial recovery. We recently reported histologic changes in the lungs of a patient who died after cesarian delivery, which were similar to a rat model of FE. In this model, we found that despite an apparent full recovery, modest fibrotic damage persisted up to 6 weeks. We tested whether at that time, an additional insult could exacerbate the effects. METHODS: Triolein (0.2 mL intravenously administered) was given to 18 rats and saline to 18 controls. Six weeks later, each group received (intraperitoneal) lipopolysaccharide (LPS, 3 mg/kg; n = 9) or saline (n = 9). At necropsy 48 hours later, lungs and organs were harvested for study. Lung parenchymal, vascular, and bronchial damage was scored by two pathologists and by Image J analysis. RESULTS: Animals given LPS after triolein showed reduced pulmonary arterial medial diameters compared with those that received LPS alone (p < 0.04). Lung small arterial patency (lumen) was reduced after triolein and even more after combined LPS and triolein (p = 0.018). Triolein increased fibrotic markers (trichrome and smooth muscle actin staining), and this was more severe after LPS. At 6 weeks, fat droplets remained in the lungs, localizing to the subpleural septa. These were smaller and more widespread after LPS. CONCLUSION: This report describes an animal model to study exacerbation of lung histopathology induced by FE using a known pulmonary toxicant, LPS (a "second hit"). Vascular and fibrotic lung damage was more severe when LPS was given to rats 6 weeks after triolein compared with LPS alone. FE rendered the lungs extra sensitive to a second hit long after apparent clinical recovery. This experimental model of fat embolism provides useful informations for the treatment of patients suffering for similar conditions.
BACKGROUND:Pulmonary fat embolism (FE) in patients after major bone fracture and other trauma may lead to acute respiratory distress, but few clinical evidence of lung injury remains, and there is a dearth of histopathologic information after the initial recovery. We recently reported histologic changes in the lungs of a patient who died after cesarian delivery, which were similar to a rat model of FE. In this model, we found that despite an apparent full recovery, modest fibrotic damage persisted up to 6 weeks. We tested whether at that time, an additional insult could exacerbate the effects. METHODS: Triolein (0.2 mL intravenously administered) was given to 18 rats and saline to 18 controls. Six weeks later, each group received (intraperitoneal) lipopolysaccharide (LPS, 3 mg/kg; n = 9) or saline (n = 9). At necropsy 48 hours later, lungs and organs were harvested for study. Lung parenchymal, vascular, and bronchial damage was scored by two pathologists and by Image J analysis. RESULTS: Animals given LPS after triolein showed reduced pulmonary arterial medial diameters compared with those that received LPS alone (p < 0.04). Lung small arterial patency (lumen) was reduced after triolein and even more after combined LPS and triolein (p = 0.018). Triolein increased fibrotic markers (trichrome and smooth muscle actin staining), and this was more severe after LPS. At 6 weeks, fat droplets remained in the lungs, localizing to the subpleural septa. These were smaller and more widespread after LPS. CONCLUSION: This report describes an animal model to study exacerbation of lung histopathology induced by FE using a known pulmonary toxicant, LPS (a "second hit"). Vascular and fibrotic lung damage was more severe when LPS was given to rats 6 weeks after triolein compared with LPS alone. FE rendered the lungs extra sensitive to a second hit long after apparent clinical recovery. This experimental model of fat embolism provides useful informations for the treatment of patients suffering for similar conditions.