Superoxide radicals and hemorrhagic shock: are intravascular radicals associated with mortality?

Superoxide radicals (SORs) are formed during hemorrhagic shock. However, the association between SOR formation and mortality remains undefined. Would neutralization of SORs during shock improve survival? Superoxide dismutase (SOD) was covalently linked to Ficoll to prolong vascular persistence and ensure ongoing neutralization of intravascular SORs. Six groups of Sprague-Dawley rats were studied. Rats were exsanguinated to a mean arterial pressure of 30 Torr, sustained for 60 min. Ficoll linked superoxide dismutase (SOD-F), 5000 Units + catalase, 150 Units, was suspended in 1 ml of saline and injected following the 60-min hypotensive period. Resuscitation followed for appropriate groups. Pretreated SOD-F rats received a 1-ml bolus prior to exsangination. Pretreatment with SOD-F did not improve survival in non-resuscitated groups despite improvement in vascular circulation (P greater than 0.10, NS). In the standard non-resuscitation group, there is also no improvement (P greater than 0.10, NS). Resuscitation with or without SOD-F significantly alters survival rates (P less than 0.025) with respect to non-resuscitated controls. However, application of SOD-F in conjunction with resuscitation does not improve survival with respect to resuscitation controls (P greater than 0.10, NS). Although SOD-F has a vascular half-life advantage over SOD, the improvement in survival is statistically non-significant. Intravascular SORs do not appear to be associated with mortality. SOR release and consequent damage to the vasculature may be preceded by a more significant intracellular damage. Intracellular SOR damage and its association with mortality in hemorrhagic shock remains an open issue.