Biological effects of intravenous vitamin C on neutrophil extracellular traps and the endothelial glycocalyx in patients with sepsis-induced ARDS

Authors

Xian Qiao, Division of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USA.
Markos G. Kashiouris, Division of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USA.
Michael L'Heureux, Division of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USA.
Bernard J. Fisher, Division of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USA.
Stefan W. Leichtle, Division of Acute Care Surgical Services, Virginia Commonwealth University, Richmond, VA 23219, USA.
Jonathon D. Truwit, Advocate Aurora Health
Rahul Nanchal, Advocate Aurora Health
Robert Duncan Hite, Division of Pulmonary Disease & Critical Care Medicine, University of Cincinnati, Cincinnati, OH 45221, USA.
Peter E. Morris, Division of Pulmonary Disease & Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Greg S. Martin, Division of Pulmonary Disease & Critical Care Medicine, Emory University, Atlanta, GA 30322, USA.
Jonathan Sevransky, Division of Pulmonary Disease & Critical Care Medicine, Emory University, Atlanta, GA 30322, USA.
Alpha A. Fowler, Division of Pulmonary Disease & Critical Care Medicine, Virginia Commonwealth University, Richmond, VA 23219, USA.

Recommended Citation

Qiao X, Kashiouris MG, L'Heureux M, et al. Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS. Nutrients. 2022;14(20):4415. Published 2022 Oct 21. doi:10.3390/nu14204415

Affiliations

Aurora St. Luke's Medical Center

Abstract

(1) Background: The disease-modifying mechanisms of high-dose intravenous vitamin C (HDIVC) in sepsis induced acute respiratory distress syndrome (ARDS) is unclear. (2) Methods: We performed a post hoc study of plasma biomarkers from subjects enrolled in the randomized placebo-controlled trial CITRIS-ALI. We explored the effects of HDIVC on cell-free DNA (cfDNA) and syndecan-1, surrogates for neutrophil extracellular trap (NET) formation and degradation of the endothelial glycocalyx, respectively. (3) Results: In 167 study subjects, baseline cfDNA levels in HDIVC (84 subjects) and placebo (83 subjects) were 2.18 ng/µL (SD 4.20 ng/µL) and 2.65 ng/µL (SD 3.87 ng/µL), respectively, = 0.45. At 48-h, the cfDNA reduction was 1.02 ng/µL greater in HDIVC than placebo, = 0.05. Mean baseline syndecan-1 levels in HDIVC and placebo were 9.49 ng/mL (SD 5.57 ng/mL) and 10.83 ng/mL (SD 5.95 ng/mL), respectively, = 0.14. At 48 h, placebo subjects exhibited a 1.53 ng/mL (95% CI, 0.96 to 2.11) increase in syndecan-1 vs. 0.75 ng/mL (95% CI, 0.21 to 1.29, = 0.05), in HDIVC subjects. (4) Conclusions: HDIVC infusion attenuated cell-free DNA and syndecan-1, biomarkers associated with sepsis-induced ARDS. Improvement of these biomarkers suggests amelioration of NETosis and shedding of the vascular endothelial glycocalyx, respectively.

Document Type

Article

PubMed ID

36297099