title: Endothelial necrosis at 1 hour postburn predicts progression of tissue injury.
abstract: Burn injury progression has not been well characterized at the cellular level. To define burn injury progression in terms of cell death, histopathologic spatiotemporal relationships of cellular necrosis and apoptosis were investigated in a validated porcine model of vertical burn injury progression. Cell necrosis was identified by high mobility group box 1 protein and apoptosis by Caspase 3a staining of tissue samples taken 1 hour, 24 hours, and 7 days postburn. Level of endothelial cell necrosis at 1 hour was predictive of level of apoptosis at 24 hours (Pearson's r = 0.87) and of level of tissue necrosis at 7 days (Pearson's r = 0.87). Furthermore, endothelial cell necrosis was deeper than interstitial cell necrosis at 1 hour (p < 0.001). Endothelial cell necrosis at 1 hour divided the zone of injury progression (Jackson's zone of stasis) into an upper subzone with necrotic endothelial cells and initially viable adnexal and interstitial cells at 1 hour that progressed to necrosis by 24 hours and a lower zone with initially viable endothelial cells at 1 hour but necrosis and apoptosis of all cell types by 24 hours. Importantly, this spatiotemporal series of events and rapid progression resembles myocardial infarction and stroke and implicates mechanisms of these injuries, ischemia, ischemia reperfusion, and programmed cell death in burn progression.
authors.affiliation: Stony Brook University School of Medicine, Stony Brook, NY 11794-8165, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Hirth
authors.forename: Steve A
authors.initials: SA
authors.lastname: McClain
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Singer
authors.forename: Richard A F
authors.initials: RA
authors.lastname: Clark
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002056:Burns / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004727:Endothelium / Q000378:metabolism / Q000473:pathology*; D024243:HMGB1 Protein / Q000378:metabolism; D007150:Immunohistochemistry; D009336:Necrosis / Q000378:metabolism; D011379:Prognosis; D013552:Swine; D013997:Time Factors
chemical_list: D024243:HMGB1 Protein; D053148:Caspase 3