ROLE OF HBOC-201 RESUSCITATION IN ISCHEMIC-REPERFUSION INJURY IN MAJOR ORGANS FROM SWINE WITH HEMORRHAGIC SHOCK

Purpose:

Nitrotyrosine is an indirect marker for free radical-mediated tissue injury. The purpose of this study was to determine whether resuscitation with bovine polymerized hemoglobin (HBOC-201) induces free radical-mediated injury in a swine model of moderately severe hemorrhagic shock.

Methods:

Yucatan swine underwent 40% hemorrhage, soft tissue injury, and fluid resuscitation with HBOC-201 or Hextend (6% hetastarch in Lactated Ringer’s solution), or no resuscitation. Tissues were harvested following euthanasia at 72 hours or post-early deaths. Nitrotyrosine in frozen sections on slides were detected by immunohistochemistry. Mean staining intensity (in comparison with normal pig tissue) was analyzed statistically using the Kruskal-Wallis Test.

Results:

No significant difference in staining intensity was detected between the 3 treatment groups in any tissue types (bowel, heart, kidney, liver, and lung). However, different tissues showed varying degrees of staining intensity, regardless of treatment type. The liver displayed the greatest and lung the lowest relative staining intensities, compared to the other tissues analyzed.

Conclusions:

Overall, the amount of nitrotyrosine was similar in HBOC-201 and Hextend-resuscitated and non-resuscitated swine. These data suggest that HBOC-201 does not increase peroxynitrite production and may not cause significant free radical-mediated reperfusion injury in hemorrhagic shock.