Effects of a novel antioxidant during resuscitation from severe blunt chest trauma

Previous work suggests that neutrophils (PMNs) and/or prostaglandins might mediate the progressive respiratory failure after severe pulmonary contusio n. Since reactive oxygen metabolites are closely associated with both these factors, we examined the actions of a novel antioxidant after swine receiv ed a unilateral injury followed by 25% hemorrhage. An infusion (2mL/kg/h in travenously x 6 h) of either polynitroxylated 5% Dextran + Tempol (PND, n = 9), 5% Dextran (D, n = 6), or lactated Ringers (LR, n = 13) was begun 60 m in post-injury to mimic 'pre-hospital resuscitation.' After 15 min, standar d resuscitation was initiated (3x shed blood as LR in 30 min) plus further LR for 6 h to maintain hemodynamics. The total LR requirement was lower wit h PND (1,772 +/- 267 mt) versus D (3,040 +/- 689, P = 0.0563) or LR (4145 /- 398, P = 0.0005). The ipsilateral bronchoalveolar lavage (BAL) PMN count with PND (8 +/- 2 x 10(5)/mL), was not different from its baseline (P = 0. 131), but the counts with D (16 +/- 3) and LR (17 +/- 4) were both higher t han their baselines (P = 0.0184 and 0.0431). Similarly, BAL protein with PN D (1,560 +/- 350 mg %) was not elevated from its baseline (P = 0.0721), but the values with D (2,560 +/- 498) and LR (2,474 +/- 899) were both higher than their baselines (P = 0.0169 and 0.0325). In the contralateral (uninjur ed) lung, the effects were similar, but the increases were less for PMNs (8 +/- 2 versus 10 +/- 2 or 14 +/- 4 x 10(5)/mL) and for protein (609 +/- 153 versus 1,955 +/- 671 or 1486 +/- 357 mg %). Despite these significant BAL changes, there was no obvious improvement in cardiopulmonary dysfunction. T hus oxidants probably have some role in the pathogenic mechanism of progres sive secondary injury after thoracic trauma, but further work is needed to determine the therapeutic potential of antioxidants because no clinical imp rovement was detected.