title: Cerebral perfusion pressure elevation with oxygen-carrying pressor after traumatic brain injury and hypotension in Swine.
abstract: BACKGROUND
  Previously, we had shown that elevation of cerebral perfusion pressure, using pressors, improved short-term outcomes after traumatic brain injury and hemorrhagic shock in swine. The current study evaluates outcomes after resuscitation with diaspirin cross-linked hemoglobin (DCLHb)--a hemoglobin-based oxygen carrier with pressor activity--in the same swine model of traumatic brain injury and hemorrhagic shock.
  
  
  METHODS
  Anesthetized and ventilated swine received traumatic brain injury via cortical fluid percussion (6-8 atm) followed by 45% blood volume hemorrhage. One hour later, animals were randomized to either a control group (SAL) resuscitated with normal saline equal to three times shed blood volume or to one of two experimental groups resuscitated with DCLHb. The two experimental groups consisted of a low-dose group, resuscitated with 250 mL of DCLHb (Hb1), and a high-dose group, resuscitated with 500 mL of DCLHb (Hb2). Animals were observed for 210 minutes postresuscitation. Outcomes evaluated were cerebral oxygenation by measuring partial pressure and saturation of oxygen in cerebrovenous blood; cerebral function by evaluating the preservation and magnitude of cerebrovascular carbon dioxide reactivity; and brain structural damage by semiquantitatively assessing beta amyloid precursor protein positive axons.
  
  
  RESULTS
  Postresuscitation, cerebral perfusion pressure was higher in the DCLHb groups (p < 0.05, Hb1 and Hb2 vs. SAL), and intracranial pressure was lower in the Hb2 group (p < 0.05 vs. SAL). Cerebrovenous oxygen level was similar in all groups (p > 0.05). At baseline, 5% carbon dioxide evoked a 16 +/- 1% increase in cerebrovenous oxygen saturation, indicating vasodilatation. At 210 minutes, this response was nearly absent in SAL (4 +/- 4%) (p < 0.05 vs. baseline) and Hb1 (1 +/- 5%), but was partially preserved in Hb2 (9 +/- 5%). There was no intergroup difference in beta amyloid precursor protein positive axons. Five of 20 SAL and 0 of 13 DCLHb animals developed brain death (flat electroencephalogram) (p = 0.05, SAL vs. DCLHb). Postresuscitation, DCLHb animals maintained higher mean pulmonary arterial pressure (28 +/- 1 mm Hg, SAL; 42 +/- 1 mm Hg, Hb1; 45 +/- 1 mm Hg, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL) and lower cardiac output (3.9 +/- 1.6 L/min, SAL; 2.6 +/- 0.1 L/min, Hb1; 2.7 +/- 0.1 L/min, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL). Three Hb2 animals died as a result of cardiac failure, and one SAL animal died as a result of irreversible shock.
  
  
  CONCLUSIONS
  In this swine model of traumatic brain injury and hemorrhagic shock, resuscitation with DCLHb maintained a higher cerebral perfusion pressure. Low-dose DCLHb (minimal increase in oxygen carriage) failed to significantly improve short-term outcome. With high-dose DCLHb (significant improvement in oxygen carriage), intracranial pressure was lower and cerebrovascular carbon dioxide reactivity was partially preserved; however, this was at the cost of poorer cardiac performance secondary to high afterload.
authors.affiliation: Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA. akmalhot@hsc.vcu.edu
authors.forename: Ajai K
authors.initials: AK
authors.lastname: Malhotra
authors.forename: John B
authors.initials: JB
authors.lastname: Schweitzer
authors.forename: Jeri L
authors.initials: JL
authors.lastname: Fox
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Fabian
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Proctor
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000187:drug effects; D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D001923:Brain Chemistry; D001926:Brain Death; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006454:Hemoglobins / Q000494:pharmacology / Q000627:therapeutic use*; D007427:Intracranial Pressure / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011897:Random Allocation; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000209:etiology*; D012965:Sodium Chloride / Q000494:pharmacology / Q000627:therapeutic use; D013552:Swine
chemical_list: D016564:Amyloid beta-Protein Precursor; D006454:Hemoglobins; D002245:Carbon Dioxide; D012965:Sodium Chloride; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin; D010100:Oxygen