Cellular responses to surgical trauma, hemorrhage, and resuscitation with diaspirin cross-linked hemoglobin in rats.
BACKGROUND
Resuscitation with acellular oxygen carrier solutions offers the potential advantage of improved oxygen delivery compared with crystalloid solutions, but the detailed consequences of improved resuscitation have not been fully evaluated. This study evaluated local and systemic cellular effects of trauma, hemorrhage, and resuscitation in a model of hemorrhage and surgical trauma.


METHODS
Rats with a 10 cm full-thickness incisional wound and a 15 mL/kg hemorrhage were either not resuscitated or resuscitated with blood or diaspirin cross-linked hemoglobin (DCLHb). Cellular proliferative responses were evaluated at 1.5, 6, 24, and 48 hours after wounding by labeling in vivo with 5-bromo-2'-deoxyuridine. Plasma levels of interleukin-6, tumor necrosis factor-alpha, and interferon-gamma were measured by bioassay or enzyme-linked immunosorbent assay (ELISA). Bacterial translocation was measured by culturing liver homogenates.


RESULTS
Trauma inhibited keratinocyte and hepatocyte proliferation at 1.5 and 6 hours, and stimulated subsequent proliferation of keratinocytes and liver nonparenchymal cells. DCLHb stimulated wound keratinocyte proliferation, attenuated the inhibition of hepatocyte proliferation, eliminated bacterial translocation to the liver, protected the intestine from ischemic damage, and induced a rapid increase of interleukin-6 during the early phase of injury.


CONCLUSIONS
Surgical trauma alone, or in combination with hemorrhage, modulated cell proliferation both in the wound and in the remote organs of intestine and liver. DCLHb enhanced wound healing and cell proliferation as well as, or better than, freshly drawn blood, which may be beneficial for trauma care.
Xu
L
L
Resuscitative Medicine Program, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA.
Sun
L
L
Rollwagen
F M
FM
Li
Y
Y
Pacheco
N D
ND
Pikoulis
E
E
Leppäniemi
A
A
Soltero
R
R
Burris
D
D
Malcolm
D
D
Nielsen
T B
TB
D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018988:Bacterial Translocation; D001794:Blood Pressure / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006454:Hemoglobins / Q000627:therapeutic use*; D006470:Hemorrhage / Q000628:therapy*; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D013154:Spleen / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing; D014947:Wounds and Injuries / Q000628:therapy*
D006454:Hemoglobins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin