title: Blood vessel occlusion in peri-burn tissue is secondary to erythrocyte aggregation and mitigated by a fibronectin-derived peptide that limits burn injury progression.
abstract: Although vascular occlusion has long been noted in peri-burn tissue, the literature is inconsistent regarding the nature of the occlusion, with articles in the 1940s claiming that erythrocytes were the culprit and in the 1980s-1990s that microthrombi were responsible. To better define the nature of vessel occlusion, we studied two porcine burn models, a hot comb horizontal injury model and a vertical injury progression model. In both cases, tissue from the first two days after burn were stained with hemotoxylin and eosin, or probed for platelets or for fibrinogen/fibrin. Erythrocytes, identified as nonstained, clumped, anuclear, 5 µm cells, occluded most blood vessels (BVs) in both burn models. In contrast, platelet or fibrinogen/fibrin antibodies stained BV occlusions minimally at early time points, and only up to 16% of deep dermal BVs at 48 hours in the hot comb model and up to 7% at 24 hours in the vertical injury progression model. Treatment of animals with a fibronectin-derived peptide (P12), which limits burn injury progression and can dilate peripheral microvasculature, reduced erythrocyte occlusion by at least 50%, speeded healing and reduced scarring. Early erythrocyte aggregation, rather than thrombosis, explains the ineffectiveness of anticoagulants to prevent burn injury progression.
authors.affiliation: School of Medicine.
authors.forename: Bilal
authors.initials: B
authors.lastname: Asif
authors.affiliation: Department of Biomedical Engineering.
authors.forename: Abdul
authors.initials: A
authors.lastname: Rahim
authors.affiliation: School of Medicine.
authors.forename: Justine
authors.initials: J
authors.lastname: Fenner
authors.affiliation: Department of Biomedical Engineering.
authors.forename: Fubao
authors.initials: F
authors.lastname: Lin
authors.affiliation: School of Medicine.
authors.forename: Douglas
authors.initials: D
authors.lastname: Hirth
authors.affiliation: Department of Biomedical Engineering.
authors.forename: John
authors.initials: J
authors.lastname: Hassani
authors.affiliation: Department of Dermatology.|Department of Emergency Medicine, Stony Brook University, Stony Brook, New York.
authors.forename: Steven A
authors.initials: SA
authors.lastname: McClain
authors.affiliation: Department of Emergency Medicine, Stony Brook University, Stony Brook, New York.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Singer
authors.affiliation: Department of Dermatology.|Dermatology Section, Medicine Service, Northport VAMC, Northport, New York.
authors.forename: Marcia G
authors.initials: MG
authors.lastname: Tonnesen
authors.affiliation: Department of Biomedical Engineering.|Department of Dermatology.
authors.forename: Richard A F
authors.initials: RA
authors.lastname: Clark
mesh_terms: D000818:Animals; D002056:Burns / Q000503:physiopathology*; D002921:Cicatrix / Q000473:pathology; D004396:Coloring Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D004903:Erythrocyte Aggregation / Q000187:drug effects*; D005353:Fibronectins / Q000494:pharmacology*; D006416:Hematoxylin / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012867:Skin / Q000098:blood supply*; D013552:Swine; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D004396:Coloring Agents; D005353:Fibronectins; D006416:Hematoxylin