Abstract | April 27, 2023

The Effects of Vigabatrin in Hemorrhagic Shock Induced Endotheliopathy and Subsequent Glycocalyx Shedding in the Lung Could Provide an Explanation for the Differential Outcomes in Trauma Between Men and Women

Aditya Vinjamuri, MS

David Engelhardt, Layola University of New Orleans; Sarah Abdullah, PhD, Department of Surgery, Tulane University School of Medicine; Farhana Shaheen, MS, Department of Surgery, Tulane University School of Medicine Zander Gerberg, Tulane University; Sharven Taghavi, MD, MPH, MS, Department of Surgery, Tulane University School of Medicine; Juan Duchesne, MD, Department of Surgery, Tulane University School of Medicine; Olan Jackson-Weaver, PhD, Department of Surgery, Tulane University School of Medicine

Learning Objectives

  1. To provide the audience a background on the Endotheliopathy of Trauma (EOT)
  2. To provide the audience with evidence on managing and combating endothelial glycocalyx shedding through the usage of pharmacological compounds.

Background:

Trauma is the leading cause of death in people under 44 years old. Hemorrhagic shock (HS) is often a consequence of trauma and contributes to morbidity and mortality in these patients. Shock-induced endotheliopathy has garnered interest recently and an aspect of this – endothelial glycocalyx shedding (EGX)- may promote coagulopathy following hemorrhage. Vigabatrin is an FDA approved anticonvulsant that inhibits GABA transaminase, preventing the metabolism of GABA to succinic-semialdehyde and subsequently to succinate. Succinate accumulates in tissues during hemorrhagic shock due to electron transport chain uncoupling and is a direct and independent predictor of death likely due to its promotion of reactive oxygen species (ROS). We hypothesize that administration of Vigabatrin prevents the buildup of succinate and promotes better physiological recovery following HS. Methods: A rat model of hemorrhagic shock and resuscitation was used to assess glycocalyx disruption in the lungs via fluorescent-labeled wheat germ agglutinin staining in frozen tissue and by syndecan-1 ELISA on plasma samples. A control group (n=5) with no Vigabatrin treatment following hemorrhage and resuscitation (H/R) was compared against an experimental group (n=5) that received Vigabatrin following hemorrhage and before resuscitation. Results:

Glycocalyx shedding (assessed by an increase in plasma syndecan-1 levels) was not improved in the vigabatrin treated group. Tissue staining of lung vasculature showed enhanced glycocalyx shedding in the vigabatrin group compared to H/R. Conclusions: Vigabatrin exacerbated glycocalyx shedding during hemorrhage/resuscitation, refuting our hypothesis. This suggests that GABA transaminase may in fact reduce succinate buildup during hemorrhage. Future experiments will be conducted to determine the effects of vigabatrin inhibiting GABA transaminase in female rats. Females have higher expression of the enzymes succinic semialdehyde dehydrogenase and GABA transaminase. Inhibiting these enzymes and analyzing glycocalyx shedding in the lungs and serum may provide insight into why females are protected during trauma and subsequent hemorrhagic shock.

 

References

https://pubmed.ncbi.nlm.nih.gov/34259440/

Posted in: Surgery & Surgical Specialties67
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