title: Ascorbic acid abrogates microparticle generation and vascular injuries associated with high-pressure exposure.
abstract: We hypothesized that pathological changes associated with elevations in annexin V-positive microparticles (MPs) following high-pressure exposures can be abrogated by ascorbic acid in a murine model. Mice exposed for 2 h to 790-kPa air and killed at 2 or 13 h postdecompression exhibited over threefold elevations in circulating MPs, as well as subgroups bearing Ly6G, CD41, Ter119, CD31, and CD142 surface proteins. There was evidence of significant neutrophil activation, platelet-neutrophil interactions, and vascular injury to brain, omentum, psoas, and skeletal muscles assessed as leakage of high-molecular-weight dextran. Prophylactic ascorbic acid (500 mg/kg ip) administration prevented all postdecompression neutrophil changes and vascular injuries. Ascorbic acid administration immediately after decompression abrogated most changes, but evidence of vascular leakage in the brain and skeletal muscle at 13 h postdecompression persisted. No significant elevations in these parameters occurred after injection of ascorbic acid alone. The findings support the idea that MP production occurring with exposures to elevated gas pressure is an oxidative stress response and that antioxidants may offer protection from pathological effects associated with decompression.
authors.affiliation: Department of Emergency Medicine, University of Maryland, Baltimore, Maryland.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Emergency Medicine, University of Maryland, Baltimore, Maryland.
authors.forename: Veena M
authors.initials: VM
authors.lastname: Bhopale
authors.affiliation: Department of Emergency Medicine, University of Maryland, Baltimore, Maryland sthom@smail.umaryland.edu.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Thom
mesh_terms: D000399:Air Pressure; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000941:Antigens / Q000096:biosynthesis; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D003665:Decompression Sickness / Q000473:pathology / Q000503:physiopathology*; D014676:Diet, Vegetarian; D004791:Enzyme Inhibitors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism
chemical_list: D017304:Annexin A5; D000941:Antigens; D000975:Antioxidants; D004791:Enzyme Inhibitors; D010718:Phosphatidylserines; D001205:Ascorbic Acid
keywords: decompression; microparticles; neutrophil activation; oxidative stress