Blood vessel occlusion with erythrocyte aggregates causes burn injury progression—microvasculature dilation as a possible therapy

Richard A.F. Clark, Justine Fenner, Arielle Sasson, Steve A. McClain, Adam J. Singer, Marcia G. Tonnesen

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Burns are dynamic injuries characterized by progressive tissue death and continuous severe pain over the course of several days. The extent of burn injury progression determines the ultimate patient outcome. Initial burns result in a central zone of necrosis surrounded by a potentially viable zone of ischemia. Several mechanisms have been proposed to explain injury progression, including oxidant and cytokine stress resulting from either ischemia/reperfusion and/or inflammation, but no proven therapy has emerged. To address the unmet need to limit burn injury progression, the root cause of this process must be delineated. For this reason, we have recently focused on post-burn blood vessel occlusion, currently ascribed to microthrombi. We have found that blood vessel occlusion is initially, mainly and persistently caused by erythrocyte aggregation. Although thermal-induced cell necrosis is the immediate cause of cell death, apoptotic cells from persistent ischemia/anoxia, admixed with inflammatory cells, form a band between viable and nonviable tissue 24 hours later. The delayed cell death by apoptosis appears to be the main attractant for inflammatory cells. Finally, we posit that fibrinogen elevation arising from inflammation provides stimulus for additional erythrocyte aggregation, further extending blood vessel occlusion. In our view this persistent occlusion with resultant prolonged tissue ischemia/anoxia, not ischemia/reperfusion, is the root cause of burn injury progression concomitant with associated severe and persistent pain. Epiviosamines, a new class of peptides, appear to selectively dilate microvasculature, and may provide therapy for burn injury progression.

Original languageEnglish
Pages (from-to)625-629
Number of pages5
JournalExperimental Dermatology
Volume27
Issue number6
DOIs
StatePublished - Jun 2018
Externally publishedYes

Keywords

  • fibronectin peptides
  • thermal injury
  • vasodilation

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