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 1 1/2 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 pharmacologic agents.