Temporal Effect of Hemoglobin Resuscitation on Sepsis Survival

Hemoglobin (Hb)-based oxygen carriers are promising resuscitation fluids for hemorrhagic shock. However, infusion of large amounts of Hb-based material could interfere with reticuloendothelial function potentiating postresuscitation sepsis mortality. We investigated the temporal relationship between hemorrhage-resuscitation and sepsis survival. Male SD rats were subjected to hemorrhage and resuscitated with shed blood volumes of purified human hemoglobin solution (HS). Sepsis was induced by cecal ligation and puncture (CLP) 24 h before, 0, 24, or 72 h after hemorrhage/resuscitation (H/R) and survival was monitored. In additional animals with or without Hb resuscitation, hepatic heme oxygenase-1 (HO-1) gene expression and HO activity were assessed. Seven-day survival for animals resuscitated with HS prior to sepsis induction was significantly higher than other groups. Animals resuscitated with HS showed hepatic HO-1 gene expression while non-HS resuscitated animals did not. In addition, hepatic HO activity...