Abstract | April 4, 2022

Succinate Induces Glycocalyx Shedding In Lung Vasculature and Alveoli: A Rat Model

Presenting Author: Robert Hazen Drury, Bachelor of Science in Nutritional Science, Medical Student, 4th Year, Tulane University School of Medicine, New Orleans, Louisiana

Coauthors: Robert Drury, BS, Medical Student, Tulane University School of Medicine, New Orleans, LA; Sarah Abdullah, MD, Graduate Student, Department of Trauma and Critical Care Surgery, Tulane University School of Medicine, New Orleans, LA; Emma Kosowski, Undergraduate Student, Tulane University, New Orleans, LA; Nicholas Bitonti, Undergraduate Student, Tulane University, New Orleans, LA; Farhana Shaheen, Medical Research Specialist, Tulane University School of Medicine, New Orleans, LA; Juan Duchesne, MD, Professor of Surgery, Chief, Department of Trauma and Critical Care Surgery, Tulane University School of Medicine, New Orleans, LA; Sharven Taghavi, MD, MPH, MS, Assistant Professor, Department of Trauma and Critical Care Surgery, Tulane University School of Medicine, New Orleans, LA; Olan Jackson-Weaver, PhD, Assistant Professor, Department of Trauma and Critical Care Surgery, Tulane University School of Medicine, New Orleans, LA.

Learning Objectives

  1. Describe the role of the glycocalyx in healthy vasculature;
  2. Discuss the prognostic benefit of measuring succinate levels in trauma patients;
  3. Examine the relationship between glycocalyx shedding and succinate levels.

BACKGROUND/KNOWLEDGE GAP: The endothelial glycocalyx (EGx) is a thin lining along the luminal surface of vasculature composed of glycoproteins and proteoglycans. In healthy blood vessels, the EGx serves several physiologic roles, including repulsion of platelets and regulation of vascular permeability. The EGx is sloughed during hemorrhagic shock and resuscitation (HSR), potentially causing coagulopathy. To date, the mechanism behind EGx shedding following HSR is unclear. Additionally, patients undergoing HSR have hypoxia-induced succinate elevation. Increased succinate levels have proven accurate in predicting morbidity and mortality following trauma. Our objective was to determine if elevated succinate levels cause EGx shedding in pulmonary tissue.

METHODS/DESIGN: In healthy rats, we injected 1,000 mg/kg of succinate into the external jugular vein. Control animals were given lactated Ringer’s. After 60 minutes, lung tissue was harvested and the rats euthanized. Lung tissue was subsequently flash frozen, sectioned via cryostat, and fixed to glass slides using methanol. Staining of the EGx was accomplished with Fluorescein isothiocyanate-labelled wheat germ agglutinin (FITC-WGA). Fluorescent Phalloidin and 4′,6-diamidino-2-phenylindole (DAPI) were used to identify vasculature. EGx intensity and thickness for both lung vasculature and alveoli were measured using ImageJ software.

RESULTS/FINDINGS: In lung vasculature, EGx was 142.3 ± 6.4 (arbitrary fluorescence units, AU) in the succinate group and 172.9 ± 7.1 AU in the control group (p value =0.002). In alveoli, EGx was 54.9 ± 0.89 AU in the succinate group and 62.4 ± 1.9 AU in the control group (p=0.0002).

CONCLUSIONS/IMPLICATIONS: EGx was significantly reduced after succinate injection in both lung vasculature and alveoli. This indicates that succinate accumulation may serve as the mechanism causing EGx shedding after HSR. Further research utilizing a HSR model is needed to determine if succinate reduction prevents EGx shedding after trauma.

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