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Pulmonary Arterial Thrombosis in a Murine Model of Blunt Thoracic Trauma

Brown, Ian E.; Rigor, Robert R.; Schutzman, Linda M.; Khosravi, Nasim; Chung, Karen; Becker, James A.; Pivetti, Christopher D.; Best, Gavin T.; Chavez, Jessica C.; Galante, Joseph M.

doi: 10.1097/SHK.0000000000001109
Basic Science Aspects
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ABSTRACT Pulmonary thromboembolic events cause significant morbidity and mortality after severe trauma. Clinically, these lesions are believed to be emboli arising secondary to deep venous thrombosis (DVT) in the lower extremities. Recently, this notion has been challenged by clinical studies, showing that pulmonary clots arise after trauma in the absence of DVT. This suggests that pulmonary blood clots arise in situ via de novo thrombosis. In the present study, we characterize a murine weight-drop model of lateral blunt thoracic trauma. Our model demonstrates severe unilateral lung contusion injury with low (10%) mortality in the absence of extrapulmonary injury, after impact with a 50-g weight dropped from 45 cm height (657 J/m2). At 24 h after injury, immunofluorescence and histological evidence revealed early pulmonary arterial thrombosis in the form of eccentric accumulation of fibrin and CD41 positive eosinophilic proteinaceous material, on both coup and contrecoup lung lobes of injured mice, indicating early thrombotic events both within and outside of the area of primary lung injury. Our model is ideal in that lateral impact enables greater impact energy to be applied to achieve significant lung contusion without significant mortality or extrapulmonary injury, and the model has additional translational value in creating thrombosis analogous to pulmonary embolism observed clinically after blunt thoracic trauma. To our knowledge, this is the first demonstration of de novo pulmonary thrombosis in a clinically translational model of blunt thoracic trauma, and supports challenges to current assumptions about the origin of pulmonary blood clots in the wake of severe traumatic injury.

Department of Surgery, University of California Davis School of Medicine, Sacramento, CA

Address reprint requests to Ian E. Brown, MD, PhD, Department of Surgery: Trauma, Acute Care Surgery, and Surgical Critical Care Division, University of California Davis Medical Center, 2315 Stockton Blvd., Suite 4206, Sacramento, CA 95817. E-mail: iebrown@ucdavis.edu

Received 9 November, 2017

Revised 28 November, 2018

Accepted 9 January, 2018

This project and all personnel were supported by UC Davis School of Medicine Department of Surgery intramural funds.

The authors reports no conflicts of interest.

© 2018 by the Shock Society