Hypertonic HBOC-201 decreases neutrophil activation after hemorrhagic shock.
OBJECTIVE
To evaluate neutrophil activation after exposure to standard HBC-201 (suspended in lactate Ringer's solution) versus HBOC-201 suspended in hypertonic 7.5% saline solution.


METHODS
We use plasma and tissue obtained from pigs subjected to controlled hemorrhagic shock and an ex vivo model of stimulated human whole blood. The pigs were resuscitated with the following (n = 8 per group) standard HBOC-201, or hypertonic HBOC-201. We used HTS 7.5%, Ringer's lactate as control resuscitation. Human blood was stimulated with same fluids. We measured the following neutrophil markers; IL-8, H2O2 in pig plasma, MPO in pig tissue, and H2O2, IL-8, and CD11b/CD18 in human whole blood.


RESULTS
H2O2 and IL-8 as well as tissue MPO were significantly decreased in pigs resuscitated with HT-HBOC-201 and HT 7.5%. Ex vivo experiments blood diluted with HTS and HT-HBOC-201 revealed lower expression of CD11b/CD18, H2O2, and IL-8. Blood diluted with HBOC-201 had a higher CD11b/CD18 expression than blood diluted with LR solution.


CONCLUSIONS
Our in vivo and ex vivo experiments indicate that HBOC-201 suspended in hypertonic 7.5% saline solution is associated with significantly less neutrophil activation when compared to standard HBOC-201 suspended in lactate Ringer's solution.
Division of Burn/Trauma/Critical Care, UT Southwestern Medical Center , Dallas, Texas , USA.
Fernando A
FA
Rivera-Chávez
Amanda
A
Lu
Ming-Mei
MM
Liu
Adil
A
Abdalla
Joseph P
JP
Minei
D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology*; D039481:CD11b Antigen / Q000097:blood; D018821:CD18 Antigens / Q000097:blood; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D018375:Neutrophil Activation / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D012462:Saline Solution, Hypertonic; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000503:physiopathology; D013552:Swine
D001802:Blood Substitutes; D039481:CD11b Antigen; D018821:CD18 Antigens; D006454:Hemoglobins; D016209:Interleukin-8; D012462:Saline Solution, Hypertonic; C096798:HBOC 201; D006861:Hydrogen Peroxide; D009195:Peroxidase