Burn trauma produces significant fluid shifts that, in turn, reduce cardiac output
and tissue perfusion. Treatment approaches to major burn injury include administration
of crystalloid solutions to correct hypovolemia and to restore peripheral perfusion.
While this aggressive postburn volume replacement increases oxygen delivery to previously
ischemic tissue, this restoration of oxygen delivery is thought to initiate a series
of deleterious events that exacerbate ischemia-related tissue injury. While persistent
hypoperfusion after burn trauma would produce cell death, volume resuscitation may
exacerbate the tissue injury that occurred during low flow state. It is clear that
after burn trauma, tissue adenosine triphosphate (ATP) levels gradually fall, and
increased adenosine monophosphate (AMP) is converted to hypoxanthine, providing substrate
for xanthine oxidase. These complicated reactions produce hydrogen peroxide and superoxide,
clearly recognized deleterious free radicals. In addition to xanthine oxidase related
free radical generation in burn trauma, adherent-activated neutrophils produce additional
free radicals. Enhanced free radical production is paralleled by impaired antioxidant
mechanisms; as indicated by burn-related decreases in superoxide dismutase, catalase,
glutathione, alpha tocopherol, and ascorbic acid levels. Burn related upregulation
of inducible nitric oxide synthase (iNOS) may produce peripheral vasodilatation, upregulate
the transcription factor nuclear factor kappa B (NF-kappaB), and promote transcription
and translation of numerous inflammatory cytokines. NO may also interact with the
superoxide radical to yield peroxynitrite, a highly reactive mediator of tissue injury.
Free radical mediated cell injury has been supported by postburn increases in systemic
and tissue levels of lipid peroxidation products such as conjugated dienes, thiobarbituric
acid reaction products, or malondialdehyde (MDA) levels. Antioxidant therapy in burn
therapy (ascorbic acid, glutathione, N-acetyl-L-cysteine, or vitamins A, E, and C
alone or in combination) have been shown to reduce burn and burn/sepsis mediated mortality,
to attenuate changes in cellular energetics, to protect microvascular circulation,
reduce tissue lipid peroxidation, improve cardiac output, and to reduce the volume
of required fluid resuscitation. Antioxidant vitamin therapy with fluid resuscitation
has also been shown to prevent burn related cardiac NF-kappaB nuclear migration, to
inhibit cardiomyocyte secretion of TNF-alpha, IL-1beta, and IL-6, and to improve cardiac
contractile function. These data collectively support the hypothesis that cellular
oxidative stress is a critical step in burn-mediated injury, and suggest that antioxidant
strategies designed to either inhibit free radical formation or to scavage free radicals
may provide organ protection in patients with burn injury.