Immune Effects of Resuscitation With Hboc-201, a Hemoglobin-Based Oxygen Carrier, in Swine With Moderately Severe Hemorrhagic Shock From Controlled Hemorrhage

Abstract

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.

Immune Safety Evaluation of Polymerized Porcine Hemoglobin (pPolyHb): A Potential Red Blood Cell Substitute

“…To the contrary, it may help to attenuate the existing inflammatory symptom. Similar results were also seen in a swine model of HBOC-201, which showed that HBOC-201 had no significant adverse or beneficial effects on immune function in a swine model of moderately severe HS and severe controlled HS [14][15][16]. Our in vitro results are consistent with in vivo results in that there is no inflammatory reaction caused by addition or infusion of pPolyHb.…”

“…Ortegon et al observed that HBOC-201 had immune-activating potential, especially enhancement of neutrophilic β 2 integrin (CD11b) expression at high concentration in vitro [13]. However, in vivo in moderate and severe controlled hemorrhagic shock (HS) in swine, with the exception of mildly increased plasma levels of the anti-inflammatory Th-2 cytokine, IL-10, HBOC-201 had minimal effects on innate immune responses [14][15][16]. As well, in trauma patients human polymerized hemoglobin (Polyheme) diminished immune activation in comparison with blood transfusions [17].…”

Repercussões celulares e imunológicas dos isômeros de ringer lactato na ressuscitação volêmica humana

“…Em alguns estudos esse composto demonstrou atividade imunomodulatória, diminuindo a migração e o acúmulo de neutrófilos no tecido pulmonar, além de apresentar baixo potencial imunogênico e inflamatório [Masuno et al 2005, Dong et al 2006. Em modelos animais, demonstrou atividade vasoconstritora e aumento da PAM mais efetivo que a obtida tanto com cristalóides quanto com colóides isotônicos [Boura et al 2003, Knudson et al 2003], porém seu uso ainda carece de estudos em humanos.…”

Importância dos carreadores de oxigênio livre de células

“…Em estudo publicado há pouco, não foi observado efeito no sistema imune decorrente da infusão de carreador de oxigênio livre de células baseado em Hb. 112 …”