title: Resuscitation of traumatic brain injury and hemorrhagic shock with polynitroxylated albumin, hextend, hypertonic saline, and lactated Ringer's: Effects on acute hemodynamics, survival, and neuronal death in mice.
abstract: Outcome after traumatic brain injury (TBI) is worsened by hemorrhagic shock (HS), but the optimal resuscitation approach is unclear. In particular, treatment of TBI patients with colloids remains controversial. We hypothesized that resuscitation with the colloids polynitroxylated albumin (PNA) or Hextend (HEX) is equal or superior to resuscitation with the crystalloids hypertonic (3%) saline (HTS) or lactated Ringer's solution (LR) after TBI plus HS in mice. C57/BL6 mice (n = 30) underwent controlled cortical impact (CCI) and 90 min of volume-controlled HS (2 mL/100 g). The mice were randomized to resuscitation with LR, HEX, HTS, or PNA, followed by 30 min of test fluid administration targeting a mean arterial pressure (MAP) of >50 mm Hg. Shed blood was re-infused to target a MAP >70 mm Hg. At 7 days post-insult, hippocampal neuron counts were assessed in hematoxylin and eosin-stained sections to quantify neuronal damage. Prehospital MAP was higher, and prehospital and total fluid requirements were lower in the PNA and HEX groups (p < 0.05 versus HTS or LR). Also, 7-day survival was highest in the PNA group, but was not significantly different than the other groups. Ipsilateral hippocampal CA1 and CA3 neuron loss did not differ between groups. We conclude that the colloids PNA and HEX exhibited more favorable effects on acute resuscitation parameters than HTS or LR, and did not increase hippocampal neuronal death in this model.
authors.affiliation: Safar Center for Resuscitation Research, Pittsburgh, Pennsylvania, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Exo
authors.forename: David K
authors.initials: DK
authors.lastname: Shellington
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayir
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Vagni
authors.forename: Keri
authors.initials: K
authors.lastname: Janesco-Feldman
authors.forename: Lil
authors.initials: L
authors.lastname: Ma
authors.forename: Carleton J
authors.initials: CJ
authors.lastname: Hsia
authors.forename: Robert S B
authors.initials: RS
authors.lastname: Clark
authors.forename: Larry W
authors.initials: LW
authors.lastname: Jenkins
authors.forename: C Edward
authors.initials: CE
authors.lastname: Dixon
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
mesh_terms: D000418:Albumins / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001810:Blood Volume / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D002452:Cell Count; D004195:Disease Models, Animal; D004632:Emergency Medical Services / Q000379:methods; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology / Q000627:therapeutic use; D007022:Hypotension / Q000188:drug therapy / Q000503:physiopathology; D007552:Isotonic Solutions / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D012151:Resuscitation / Q000379:methods; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic / Q000494:pharmacology* / Q000627:therapeutic use; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000418:Albumins; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic; C117059:polynitroxyl-albumin
references.citation: J Cereb Blood Flow Metab. 2001 Jul;21(7):847-56
references.pmid: 11435797
references.citation: N Engl J Med. 2004 May 27;350(22):2247-56
references.pmid: 15163774
references.citation: Stroke. 2000 Apr;31(4):961-7
references.pmid: 10754006
references.citation: Crit Care Med. 1991 Mar;19(3):364-72
references.pmid: 1705491
references.citation: Acta Anaesthesiol Scand. 2007 Oct;51(9):1194-201
references.pmid: 17711565
references.citation: J Trauma. 2008 Feb;64(2):348-57
references.pmid: 18301197
references.citation: J Neurosurg. 1988 Jul;69(1):72-81
references.pmid: 3379478
references.citation: J Am Coll Surg. 2007 Feb;204(2):261-75
references.pmid: 17254930
references.citation: J Neurotrauma. 1996 Jul;13(7):371-83
references.pmid: 8863193
references.citation: J Neurosurg. 1992 Jan;76(1):91-8
references.pmid: 1727174
references.citation: Surg Neurol. 1993 Sep;40(3):196-206
references.pmid: 8346473
references.citation: J Trauma. 2004 Sep;57(3):547-54
references.pmid: 15454801
references.citation: J Cereb Blood Flow Metab. 2008 Jun;28(6):1114-26
references.pmid: 18319733
references.citation: J R Coll Surg Edinb. 1982 Sep;27(5):292-8
references.pmid: 7143298
references.citation: Neuroreport. 2001 Nov 16;12(16):3609-12
references.pmid: 11733721
references.citation: Neurosurg Focus. 2007 May 15;22(5):E5
references.pmid: 17613236
references.citation: Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H167-75
references.pmid: 16443674
references.citation: J Cereb Blood Flow Metab. 1998 Sep;18(9):1022-31
references.pmid: 9740106
references.citation: Surgery. 2004 Aug;136(2):355-63
references.pmid: 15300202
references.citation: J Surg Res. 1991 Mar;50(3):284-92
references.pmid: 1999918
references.citation: Free Radic Biol Med. 1998 Jul 15;25(2):153-9
references.pmid: 9667490
references.citation: J Neurosurg. 1988 Jul;69(1):82-91
references.pmid: 2454305
references.citation: J Trauma. 2002 Nov;53(5):968-77
references.pmid: 12435951
references.citation: J Interferon Cytokine Res. 1999 Jul;19(7):791-5
references.pmid: 10454350
references.citation: Brain Res. 1989 Jan 16;477(1-2):211-24
references.pmid: 2702484
references.citation: Exp Neurol. 2002 Aug;176(2):355-63
references.pmid: 12359177
references.citation: J Neurotrauma. 2009 Jun;26(6):889-99
references.pmid: 18781889
references.citation: J Trauma. 1993 Feb;34(2):216-22
references.pmid: 8459458
references.citation: Free Radic Biol Med. 2002 Apr 15;32(8):712-9
references.pmid: 11937297
references.citation: N Engl J Med. 2007 Aug 30;357(9):874-84
references.pmid: 17761591
references.citation: Prehosp Emerg Care. 2008;12 Suppl 1:S1-52
references.pmid: 18203044
references.citation: J Trauma. 2003 Jul;55(1):94-105
references.pmid: 12855887