reconstitute it under field conditions. Currently, preclinical trials are needed to determine the optimal volume expansion, rate of excretion, and optimal chelator concentration for continued use of these compounds.

Other compounds described to inhibit iron chelation include tirilazad mesylate, a 21-aminosteroid. Infusion of these aminosteroids prior to fluid resuscitation from hemorrhagic shock have been shown to preserve endothelial structural integrity and to improve outcome, despite no change in neutrophil influx into tissue (Eversole, 1993; Fleckenstein et al., 1991).

Inhibition of Polymorphonuclear Neutrophil Adherence and Activation

Indirect evidence for the role of neutrophils as a source of free radicals and deleterious mediators in trauma with hemorrhagic shock has been provided by studies that use monoclonal antibodies to inhibit specific adhesion molecules involved in the tethering, adherence, and activation of this cell population. Several studies have shown improved hemodynamic performance, reduced cellular injury, a downregulation of the overall inflammatory response, and improved survival in animals resuscitated from hemorrhagic shock with lactated Ringer's solution plus the R6.5 antibody, a specific inhibitor of intracellular adhesion molecule 1 (Mileski et al., 1990, 1991). This antibody strategy reduced the level of adherence of polymorphonuclear neutrophils in the microcirculation of several organs and prevented the transmigration of activated leukocytes into peripheral tissues (Mileski et al., 1990). The application of these monoclonal antibodies with fluid resuscitation in several other types of trauma confirmed the hemodynamic and cardioprotective effects (Horton et al., 1996).

Nitric Oxide Inhibition

Hemorrhagic shock and resuscitation activate the inducible isoform of nitric oxide synthase (iNOS), and selective inhibition of iNOS provides beneficial effects in several types of circulatory shock. Of particular concern is generation of the highly toxic compound peroxynitrite, which is formed by the interaction of nitric oxide and the superoxide radical. Both pharmacologic approaches and iNOS-knockout animals have confirmed that nitric oxide and peroxynitrite play significant roles in cellular injury and organ dysfunction after fluid resuscitation from hemorrhagic shock. Recent strategies have been directed toward specific scavenging of peroxynitrite in an effort to delay vascular decompensation and to reduce cellular energetic failure in severe hemorrhagic shock. In this regard, MEG is a potent inhibitor of iNOS and effectively scavenges peroxynitrite. MEG added to fluid used for resuscitation from shock diminished the shock-related increase in plasma nitrite/nitrate and 6-keto-prostaglandin F 1-α levels, improved arterial blood pressure, and ablated the vascular hyporeactivity associated with crystalloid resuscitation from shock. Lactated Ringer's solution re-

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