title: Resuscitation from hemorrhagic shock with HBOC-201 in the setting of traumatic brain injury.
abstract: Outcomes after mild or moderate head trauma are worsened with associated hypotension, and secondary brain injury can be reduced with timely resuscitation. This study was performed to investigate HBOC-201 as a resuscitation therapy in a combined hemorrhagic shock and brain injury model. Anesthetized rats sustained moderate brain injury using a controlled cortical impact device, followed by rapid hemorrhage to a mean arterial pressure of 30 mmHg. After 30 min of hypotension, animals were resuscitated with HBOC-201, autologous shed blood (SB), or lactated Ringer solution (LR). Brain injury was assessed by measurements of cerebral blood flow (CBF) and cerebral vasoreactivity to hypercapnia (CVH) using a laser Doppler flowmeter. Contusion volume was evaluated histologically, and cerebral edema was determined by total water content. The HBOC rats required significantly less resuscitation volume versus LR and SB. The CBF was significantly diminished at 60 min after resuscitation with HBOC (70.1% +/- 3.8% baseline) compared with LR (105.8% +/- 10.1% baseline; P < 0.01) and SB (96.8% +/- 5% baseline; P < 0.05). The CVH was preserved in the HBOC and SB groups. The CVH was significantly diminished compared with baseline in the LR group at 30 min after resuscitation and showed a significant loss compared with HBOC at 60 min after resuscitation. The contusion volume for HBOC (45.1 mm3) and SB (35.1 mm3) was less than LR (63.5 mm3, P < 0.01). Although CBF was diminished after resuscitation in the HBOC group, HBOC-treated animals maintained CVH and experienced significantly smaller contusion volume than those treated with LR. These results suggest that resuscitation with HBOC-201 protects autoregulatory mechanisms and may reduce secondary brain injury in traumatic brain injury.
authors.affiliation: Department of Surgery, Section of Trauma Burns and Surgical Critical Care, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. Jeffrey.Kerby@ccc.uab.edu
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Kerby
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Sainz
authors.forename: Fangyi
authors.initials: F
authors.lastname: Zhang
authors.forename: Anne
authors.initials: A
authors.lastname: Hutchings
authors.forename: Shane
authors.initials: S
authors.lastname: Sprague
authors.forename: Farrokh R
authors.initials: FR
authors.lastname: Farrokhi
authors.forename: Minnette
authors.initials: M
authors.lastname: Son
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000627:therapeutic use*; D001930:Brain Injuries / Q000188:drug therapy*; D002560:Cerebrovascular Circulation; D006454:Hemoglobins / Q000378:metabolism / Q000627:therapeutic use*; D006470:Hemorrhage / Q000517:prevention & control; D008297:Male; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C096798:HBOC 201; D010100:Oxygen