Immune effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers (HBOC) in a swine model of severe controlled hemorrhagic shock.

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.

Innate immune responses in Swine resuscitated from severe traumatic hemorrhagic shock with hemoglobin-based oxygen carrier-201.

Hemoglobin-based oxygen carrier-201 transports oxygen and improves survival in swine with hemorrhagic shock, but has potential to be immune activating. Herein, we evaluated HBOC-201's immune effects in swine with more severe hemorrhagic shock due to soft tissue injury and 55% blood volume catheter withdrawal over 15 minutes followed by fluid resuscitation at 20 minutes with HBOC-201, Hextend, or no treatment (NON) before hospital arrival. Survival rates were similar with HBOC-201 and Hextend (p > 0.05), but were higher than in (p = 0.007). There were no significant group differences in blood cell count, percentages of leukocyte sub-populations and immunophenotype (CD4:CD8 ratio), adhesion markers expression (neutrophil CD11b; monocyte or neutrophil CD49d) and apoptosis. There was a trend to higher plasma IL-10 in HBOC-201 and groups vs. Hextend. We conclude that in swine with severe controlled HS and soft tissue injury, immune responses are similar with resuscitation with HBOC-201 and Hextend.