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Doxycycline Inhibits Hemorrhagic Shock Induced Fluid Leak and Derangements in Microvascular Endothelial Cells
Katie Wiggins-Dohlvik, MD, S Naqvi, K Granfor, C Anasooya Shaji, H Alluri, V Govande, MR Beeram, ML Davis and B Tharakan, Texas A&M Health Science Center, College of Medicine and Baylor Scott and White Health, Temple TX

Abstract:
Trauma is the leading cause of pediatric mortality. Among such patients, hemorrhagic shock (HS) is common. The pathophysiology induced by HS is complex and known to induce vascular hyperpermeability. The mechanisms that regulate this process are unclear. We hypothesized that Reactive Oxygen Species (ROS) may be pivotal therein and that such damage can be attenuated with doxycycline, which has been shown to be a potential antioxidant. Rats were divided into sham and HS groups: serum and tissue were collected after one hour of shock and one hour of resuscitation. Rat lung microvascular endothelial cells (RLMEC) were grown and divided into groups treated with sham serum, HS serum, sham serum plus doxycycline, and HS serum plus doxycycline. Albumin flux across the monolayers was obtained as a marker of monolayer permeability. ROS formation was assayed. The structural proteins ?-catenin and filamentous-actin were imaged with confocal microscopy. Statistical analysis was conducted using Student's t-test and ANOVA. HS serum significantly increased monolayer permeability (p< 0.05) and ROS formation (p< 0.05). Immunofluorescence images showed HS serum induced disruption of ?-catenin and incited formation of filamentous-actin stress fibers. Doxycycline attenuated these derangements. Hemorrhagic shock induces microvascular hyperpermeability, induces Reactive Oxygen Species formation, and causes changes in endothelial cell structure. Doxycycline mitigates these derangements. These data highlight the possibility of doxycycline's anti-ROS properties and illuminate the potential role of Reactive Oxygen Species in the pathophysiology of fluid leak. Our findings pave the way for better understanding and treatments of vascular hyperpermeability in the setting of hemorrhagic shock.
Objective:
The learner will be able to better understand fluid leak seen in hemorrhagic shock, possible contributing factors, and strategies to combat these derangements.
Objective Content: The presentation will discuss the manner in which MMP-9 contributes to vascular permeability and how doxycycline may counter-act these actions.


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