title: Effects of a novel antioxidant during resuscitation from severe blunt chest trauma.
abstract: Previous work suggests that neutrophils (PMNs) and/or prostaglandins might mediate the progressive respiratory failure after severe pulmonary contusion. Since reactive oxygen metabolites are closely associated with both these factors, we examined the actions of a novel antioxidant after swine received a unilateral injury followed by 25% hemorrhage. An infusion (2mL/kg/h intravenously 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 min post-injury to mimic 'pre-hospital resuscitation.' After 15 min, standard 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 with PND (1,772+/-267 mL) 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 than their baselines (P = 0.0184 and 0.0431). Similarly, BAL protein with PND (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 (uninjured) 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. Thus oxidants probably have some role in the pathogenic mechanism of progressive secondary injury after thoracic trauma, but further work is needed to determine the therapeutic potential of antioxidants because no clinical improvement was detected.
authors.affiliation: Department of Surgery and Physiology, University of Tennessee Health Science Center, Memphis 38163, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Maxwell
authors.forename: J B
authors.initials: JB
authors.lastname: Gibson
authors.forename: T C
authors.initials: TC
authors.lastname: Fabian
authors.forename: K G
authors.initials: KG
authors.lastname: Proctor
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D003911:Dextrans / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics; D007552:Isotonic Solutions / Q000008:administration & dosage; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D055370:Lung Injury; D008297:Male; D009504:Neutrophils; D011506:Proteins / Q000378:metabolism; D012151:Resuscitation / Q000379:methods*; D000077325:Ringer's Lactate; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy; D013113:Spin Labels; D013552:Swine; D013898:Thoracic Injuries / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D014949:Wounds, Nonpenetrating / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D003911:Dextrans; D007552:Isotonic Solutions; D011506:Proteins; D000077325:Ringer's Lactate; D013113:Spin Labels; C001803:tempol