The purpose of this study was to test whether polynitroxylation (PN) improved the therapeutic profile of hemoglobin-based oxygen-carrying compounds (HBOCs) that were unpolymerized (ααHb) or 70% polymerized (polyHb) in a clinically relevant model that combines pulmonary injury and reperfusion. To our knowledge, four different HBOC formulations have never been compared in the same trauma model.
Anesthetized, ventilated swine (n = 45) received a unilateral lung contusion + 25% hemorrhage. After 60 minutes, 250 mL of either PNααHb (n = 5), ααHb (n = 10), PNpolyHb (n = 6), polyHb (n = 5), or normal saline (NaCl, n = 10) was administered for 20 minutes, followed by standard crystalloid resuscitation for 30 minutes, and supplemental crystalloid as required for 6 hours to maintain heart rate <100 beats/min and mean arterial pressure >70 mm Hg.
Nine of 45 deaths occurred before resuscitation. Survival time was 395 minutes with NaCl versus 303 minutes with ααHb (p = 0.03) or 238 minutes with PNααHb (p = 0.04). With both polymerized HBOCs, survival was 480 minutes (polyHb vs. ααHb, p = 0.005; PNpolyHb vs. PNααHb, p = 0.006). All HBOCs were pressors (all p < 0.05) and all reduced the supplemental fluid required to maintain systemic hemodynamics during resuscitation (all p < 0.05). By 90 minutes postresuscitation, cardiac index was 112% of baseline with NaCl (p < 0.02), but was 78% with ααHb (p = not significant), 63% with PNααHb (p < 0.01), 79% with PNpolyHb (p < 0.01), and 67% with polyHb (p < 0.02). Relative to NaCl, no HBOC altered trauma-induced neutrophilia, thrombocytopenia, or the trauma-induced increases in bronchoalveolar lavage protein or bronchoalveolar lavage neutrophils.
After resuscitation from chest trauma, we observed the following: (1) all HBOCs reduced fluid requirements and increased right and left ventricular afterload versus NaCl, which further compromised an already marginal cardiac performance; (2) mortality was less with polyHbs relative to ααHb, but the pressor action was unchanged; (3) the pressor action was less with polynitroxylated compounds relative to the unmodified HBOC, but this chemical modification had no effect on mortality; and (4) the pressor action of HBOCs must be attenuated by strategies other than polymerization or polynitroxylation for these compounds to be safe, effective resuscitants in humans.
From the Departments of Surgery (J.B.G., T.C.F.) and Physiology (K.G.P.), University of Tennessee Health Science Center, Memphis, Tennessee, and Department of Surgery (R.A.M.), University of Tennessee Erlanger Medical Center, Chattanooga, Tennessee.
Submitted for publication February 10, 2000.
Accepted for publication May 1, 2000.
Address for reprints: Kenneth G. Proctor, PhD, Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163. E-mail: email@example.com.
Supported, in part, by Grant N00014–96-1–0282 from the Office of Naval Research.
Presented at the 13th Annual Meeting of the Eastern Association for the Surgery of Trauma, January 12–15, 2000, Sanibel, Florida.