The pulmonary vessel adventitia: role in the pathology of fat embolism (LB511)

Abstract

Background/rationale: Fat embolism (FE) a clinical presentation where fat droplets from site of injury are intravasated into the venous system and sequestered into the lungs is common following long bone fractures. Although considered subclinical, severe cases occur with mortality. Our animal models have shown progressive pulmonary fibrosis from FE with early respiratory distress. Vascular adventitial layer has recently been identified as a first responder to vascular stress or injury, characterized by chemokine/cytokine generation that activates functional vessel wall remodeling. Does FE progress through adventitial responses? Methods. With University clearance, FE was created in rats with 0.2 mL marrow‐like lipid I.V. (triolein) [n=18]or saline [n=18) followed at 6 weeks by a “second hit” on the lung by low dose LPS or saline (9 each dose/group). Lungs were studied at 48 hr following the LPS or saline, with emphasis on the pulmonary response to FE, exacerbated or not by LPS. BAL cells were counted, vessels stained (H&E, trichrome). Arterial layers were measured at 400x by researchers unaware of treatment groups.Results: PMN counts increased by 15% in the FE group over saline at 6 weeks. LPS produced a PMN BAL count threefold over saline. FE‐treated lungs at 6 weeks were inflamed with greater cellularity in the adventitial layer. When LPS was added to FE‐treated lungs the adventitia thickness difference vs saline showed p=0.11. Controls alone showed p=0.58.Summary: Arterial adventitial layer in lungs after FE is increased in thickness and cellularity; added LPS increases thickness. Percent PMN in BAL is significantly elevated by FE alone. Identification of the cells (and their secretions) that proliferate in the adventitia after FE remains an immediate goal.Grant Funding Source: Geldmacher Foundation Grant to GS