Long term Impact of Fat emboli in a Rat Model of Fat Embolism Syndrome

Abstract

IntroductionFat embolism syndrome (FES) can occur after events that disrupt organ or integument systems such as orthopedic surgery or trauma that result in the release of fat emboli into the microcirculation. The most common clinical manifestation is damage to the lung, brain and retina and induction of systemic inflammation. 86% of patients with FES present with neurological symptoms, often preceding a diagnosis of pulmonary embolism. While the acute symptoms of FES are treated aggressively, the long‐term impact of emboli on the brain is poorly understood. To study the short and long‐term impact of fat emboli (FE) we examined histological changes and distribution of emboli in the brains and lungs 48 hours and 10 weeks after intravenous triolein administration in rats, an established model of fat embolism.Materials and Methods24 anesthetized Sprague Dawley rats (250–330 g) received either 0.2 ml intravenous triolein or saline (N=12 each). Tissue was collected after 48 hours or 10 weeks (N=6/group) snap frozen, sectioned and stained for Oil Red O, and counterstained with Hematoxylin and Eosin. Sections were imaged at 400 x magnification and quantified by two researchers, blind to section identity. Counts were decoded by an independent observer, and statistically compared utilizing a Student’s T‐test.ResultsEmboli were observed in brains of both control and experimental groups. Quantitative evaluation of emboli at 48‐hour post injection did not show any differences in size and location of large diameter emboli (> 25uM) between groups, confirming previous reports. However, an increase in micro emboli (<20uM) of experimental versus control brains was observed. At 10 weeks post injection, a significant increase in the proportion of large emboli was observed in the cerebral cortex, brainstem, in the meningeal spaces and the arteries (p<0.05). These results are in contrast to findings in the lungs where a significant difference in the proportion of large emboli was observed in the lungs at 48 hours and 10‐weeks compared to controls. At both time intervals severe arterial and septal inflammation was observed as previously reported. Histological signs of inflammation were not observed in the brain but moderate meningeal vascular inflammatory reaction was present.ConclusionLarge emboli were observed in the lung at 48 hours and 10 weeks but only micro emboli were observed in the brain at 48 hours with little penetrance of large emboli. At 10 weeks larger emboli were evident in the brain. In contrast to the significant inflammatory reaction observed in lung at both 48 hours and 10‐weeks, only a mild inflammatory reaction was observed in the meninges at 48 hours that was absent at 10‐weeks. Further studies will investigate the long‐term impact of emboli on the anatomical or behavioral outcome in brain.Support or Funding InformationCatherine T. Geldmacher Foundation, St. Louis, MO.; UMKC School of Medicine startup funds (A. Paula Monaghan).