Immune Effects of Decreasing Low-Molecular Weight Hemoglobin Components of Hemoglobin-Based Oxygen Carriers (HBOC) in a Swine Model of Severe Controlled Hemorrhagic Shock

Abstract

Hemoglobin-based oxygen carriers (HBOCs) show potential as safe, efficacious, pre-hospital resuscitation fluids. The major criticism of HBOC-201 is its vasoactive property, attributed partially to low-molecular weight (low-MW) tetrameric/dimeric (TD) hemoglobin (Hb) in HBOC solution. Here we sought to determine whether resuscitation with decreasing concentrations of low-MW Hb component of HBOC affects immune responses in hemorrhagic swine. 28 anesthetized swine underwent a soft muscle crush and controlled hemorrhage of 55% blood volume, followed by resuscitation with HBOC containing 31%, 2%, or 0.4% low-MW Hb in four 10 ml/kg infusions at 20, 30, 45 and 60 minutes before hospital arrival at 75 minutes. IL-10, cell activation and adhesion markers and CD4:CD8 ratio remained unchanged in all 3 groups compared to baseline. Leukocyte apoptosis was equally elevated across all groups. Purification from 31% to 0.4% low-MW Hb in HBOC solution did not alter immune effects in a swine model of severe controlled hemorrhagic shock.

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].…”