Abstract Rationale Hemorrhagic shock is a life-threatening condition caused by rapid blood loss, resulting in tissue hypoperfusion, oxidative stress, and multi-organ dysfunction. Despite advances in resuscitation, outcomes remain poor. Previous studies have shown that females show greater resistance to oxidative injury than males. Novel phospholipid nanoparticles, including VBI-1, have shown promise in stabilizing hemodynamics and mitigating oxidative injury (OI). Methods We employed the Femoral Artery Catheterization and Reanimation Technique (FACART) in rats to model hemorrhagic shock and reanimation. In this model, blood is rapidly removed from rats to the point of loss of spontaneous respiration. This is followed by rapid intra-arterial infusion of VBI-1, resulting in reanimation with return of breathing and a sustained normal blood pressure. Animal groups were sham, and those that received infusions of either shed blood or VBI-1 in a volume equal to the volume of blood removed. DNA injury due to OI was assessed across multiple organs using 8-hydroxyguanosine immunofluorescence. Discriminant analysis was performed to evaluate sex-specific patterns. Results Discriminant analysis of reactive oxygen species (ROS) data revealed distinct separation among SHAM, blood loss, and VBI-1 groups, with VBI-1 clustering closer to SHAM, consistent with a protective effect. When sexes were combined, the model achieved 77% accuracy, while sex-stratified analyses improved classification to 100% in males and 97% in females, highlighting sex-specific ROS patterns. Organ contributions also differed by sex: kidney responses were most influential in males, lung responses in females, and liver and heart consistently contributed across both sexes. Conclusion Given the current literature we expected to find that all organs of females would be more resistant to OI than males. Instead, we found that OI caused by the infusion of blood to be surprisingly heterogeneous and organ specific. VBI-1 demonstrates protective properties, in all circumstances supporting its potential efficacy in improving outcomes after hemorrhagic shock. The etiologies of this difference will be the subject of future studies. This abstract is funded by: Department of Defense
Kumaresan et al. (Fri,) studied this question.