Immune effects of resuscitation with HBOC-201, a hemoglobin-based oxygen carrier, in swine with moderately severe hemorrhagic shock from controlled hemorrhage.
HBOC-201, a hemoglobin-based oxygen carrier, improved physiologic parameters and survival in hemorrhagic shock (HS) animal models. However, resuscitation from HS and the properties of different fluids influence immune responses. The aim of this study was to determine if HBOC-201 significantly alters immune function in traumatic HS. Anesthetized pigs underwent soft tissue injury, controlled hemorrhage of 40% of blood volume, and resuscitation with HBOC-201 or Hextend, or no resuscitation. Sequential whole-blood samples were collected for analyses of leukocyte differential (hematology analyzer), T-lymphocyte subsets (CD3, CD4, and CD8) (FACS), lymphocyte adhesion marker CD49d (alpha4-integrin) expression (FACS), plasma cytokines-tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10-(ELISA), and lymphocyte apoptosis (annexin-V/propidium iodide staining) (FACS). Statistical analyses were performed by the mixed procedure. Total WBC counts decreased posthemorrhage in both resuscitation groups. Lymphocyte percentages decreased and PMN percentages increased around 4 h posthemorrhage in all groups. CD3 cells decreased in all groups, but CD4 and CD8 cells decreased only in the resuscitation groups. TNF-alpha levels were not detectable in any groups. IL-6 levels were similar across treatment groups (P > 0.05); however, IL-10 levels were higher in the HBOC group, as early as 1 h posthemorrhage (P = 0.04). Increases in lymphocytic CD49d expression levels and apoptosis occurred only in nonresuscitation and Hextend groups, respectively (P < or = 0.01). In comparison with Hextend, HBOC-201 had no significant adverse or beneficial effects on immune function in this model of moderately severe HS in swine, suggesting that it may be safe as a resuscitation fluid in HS patients.
Dong
Feng
F
Naval Medical Research Center, Silver Spring, MD 20910-7500, USA. hallc@nmrc.navy.mil
Hall
Carrie H
CH
Golech
Suzanne A
SA
Philbin
Nora B
NB
Rice
Jennifer P
JP
Gurney
Jennifer
J
Arnaud
Francoise G
FG
Hammett
Michael
M
Ma
Xia
X
Flournoy
W Shannon
WS
Hong
Jiang
J
Kaplan
Lewis J
LJ
Pearce
L Bruce
LB
McGwin
Gerald
G
Ahlers
Stephen
S
McCarron
Richard
R
Freilich
Daniel
D
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001802:Blood Substitutes / Q000008:administration & dosage* / Q000009:adverse effects; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006454:Hemoglobins / Q000008:administration & dosage* / Q000009:adverse effects; D039441:Integrin alpha4 / Q000276:immunology; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D001802:Blood Substitutes; D016207:Cytokines; D006454:Hemoglobins; D039441:Integrin alpha4; C096798:HBOC 201