Evidence for an early free radical-mediated reperfusion injury in frostbite

Paul N. Manson, Richard Jesudass, Louis Marzella, Gregory B. Bulkley, Michael J. Im, Kailash K. Narayan

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Frostbite is characterized by acute tissue injury induced by freezing and thawing. Initial complete ischemia is followed by reperfusion and later, tissue necrosis. These vascular events support the hypothesis that free radical-mediated reperfusion injury at thawing might contribute to tissue necrosis after frostbite in a manner similar to that seen after normothermic ischemia. To test this hypothesis, rabbit ears were frozen at -21°C for 30, 60, 90, or 120 s and rewarmed at room temperature (22°C). Rabbits were treated "blindly" with saline alone, highly purified, pharmaceutical grade superoxide dismutase (SOD), allopurinol, or deferoxamine. The area of ear necrosis was determined 3 weeks after frostbite by "blinded" morphometry. The administration of SOD at the time of thawing significantly improved viability in ears frozen for 60 and 90 s, but not in those frozen for 30 or 120 s. Deferoxamine also improved viability in ears frozen for 60 s. Allopurinol did not significantly affect ear survival. Electron micrographs showed the appearance of severe endothelial cell injury beginning during freezing and extending through early reperfusion. Later, neutrophil adhesion, erythrocyte aggregation, amd microvascular stasis were seen. These findings suggest that free radical-mediated reperfusion injury has a role in frostbite, and quantitate the proportion of the injury that is due to this mechanism.

Original languageEnglish (US)
Pages (from-to)7-11
Number of pages5
JournalFree Radical Biology and Medicine
Issue number1
StatePublished - 1991


  • Cold injury endothelial cell injury
  • Free radicals
  • Freezing injury
  • Frostbite
  • Ischemic injury
  • Microvascular injury
  • Reperfusion injury

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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