Efficacy of leupeptin, superoxide dismutase, and verapamil in modulating delayed reperfusion damage after burn injury

Zhao Fan Xia, Robert E. Barrow, Feng He, Lyle D. Broemeling, David N. Herndon

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Reperfusion damage has been identified as an important factor in multiorgan failure after severe burn injury. We wondered if leupeptin, a protease inhibitor, Superoxide dismutase (SOD), a scavenger of free oxygen radicals, or verapamil, a calcium antagonist, would protect the cellular energy metabolism when they were given with fluid resuscitation that was delayed 6 hours after a severe burn injury. Fifty male rats weighing 280 to 300 gm received a 50% third-degree scald burn. Ten of these received fluid resuscitation at 30 minutes and l½ hours after injury, and 40 received delayed fluid resuscitation at 6 and 7 hours after injury. Thirty of these 40 rats were given leupeptin (n = 10), SOD (n = 10), or verapamil (n = 10). Heart, liver, and kidney tissue samples were obtained 8 hours after injury; adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate were measured; and the energy charge potential was calculated. Tissue water content (TWC) in lung and skeletal muscle was also determined. The adenine nucleotide pool and the energy charge potential in heart, liver, and kidney tissue were all significantly decreased (p < 0.01) in rats receiving delayed fluid resuscitation compared with those receiving early resuscitation. Leupeptin was effective in protecting the heart against reperfusion damage, and verapamil and leupeptin showed some efficacy in protecting kidney tissue. Liver tissue, however, showed no protective response with therapy. TWC was significantly decreased (p < 0.01) in skeletal muscle with SOD treatment, and though all treatments appeared to keep lung water content reduced, none was significant at p < 0.01. We thus conclude that both the decreases in heart and kidney adenine nucleotides and the increase in TWC that are caused by delayed fluid resuscitation can be attenuated with appropriate pharmacologie agents.

Original languageEnglish (US)
Pages (from-to)530-537
Number of pages8
JournalJournal of Burn Care and Rehabilitation
Issue number5
StatePublished - Sep 1992

ASJC Scopus subject areas

  • Surgery
  • General Nursing
  • Emergency Medicine
  • Rehabilitation
  • General Health Professions


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