Endothelial Injury Mechanism in Elderly Patients Undergoing Major Surgery
Status:
Completed
Trial end date:
2020-10-31
Target enrollment:
Participant gender:
Summary
The incidence of postoperative cognitive injury is high in elderly patients, especially after
major surgery. The relevant pathophysiological mechanisms are still unclear, and the possible
mechanisms that have been proposed so far include inflammation, neurotransmitter imbalance
and metabolic disorders. In recent years, clinical studies of acute brain dysfunction after
vascular endothelial injury have attracted attention.
Degradation of the endothelial glycocalyx layer and subsequent shedding of its constituents
is seen as an early marker of endothelial injury, and may increase vascular permeability.Many
preclinical and clinical studies have demonstrated an association between inflammatory
cytokines such as TNF-α, IL-1β, IL-6, and IL-10 and glycocalyx degradation biomarkers.
The scholars found evidence of plasma endothelial injury after abdominal open surgery in the
elderly. Dexmedetomidine could attenuate stress response such as TNF-α, IL-1β and IL-6. Based
on the above evidence, we hypothesize that elderly patients experience inflammatory response
secondary to surgical traumatic stress after major surgery, greatly increasing the degree of
endothelial injury (heparan sulphate and syndecan-1), reducing brain perfusion while
increasing Blood-brain barrier permeability (S100B level), promoting the release of cytokines
Interleukin-2(IL-2), Interleukin-6(IL-6), tumor necrosis factor-alpha(TNF-α) ,and vascular
endothelial growth factor (VEGF) while reducing brain-derived neurotrophic factor(BDNF)
synthesis, then leading to postoperative acute spasm. We would test the hypothesis that can
reverse these effects and improve cognitive deficits.
Phase:
Phase 4
Details
Lead Sponsor:
The First Affiliated Hospital of Anhui Medical University