BACKGROUND: Previous research suggested that splanchnic hypoperfusion occurs after resuscitation with certain acellular hemoglobin solutions. We examined the influence of maltose content and oxygen affinity on resuscitation with various hemoglobin polyoxyethylene conjugate solutions after hemorrhage. METHODS: Fifteen swine underwent hemorrhage and equal volume resuscitation with pyridoxalated hemoglobin polyoxyethylene conjugate containing 0% or 8% maltose, or low P50 conjugate, which also contained 8% maltose. Five control animals were monitored but not bled. Regional blood flow was determined by using radioactive microspheres, gastric mucosal perfusion was estimated with tonometry, and gut histopathology was evaluated. RESULTS: All hemoglobin solutions produced vasoconstriction, manifested by elevated mean systemic and pulmonary artery pressures without a significant decrease in cardiac index compared with the sham group. Resuscitation with maltose-containing solutions elevated arterial and regional PCO2 and depressed arterial pH and gastric pHi (p < 0.05 for all). Splanchnic and renal blood flows were reduced in the low P50 + 8% maltose group (p < 0.05 vs. sham and baseline for renal blood flow), possibly indicating greater regional vasoconstriction in this group. Ileal mucosal damage was more severe in the maltose-containing groups and correlated with decreased pHi. CONCLUSION: Vasoconstriction occurred in all groups but was more severe in the low P50 + 8% maltose group. Maltose-containing solutions caused respiratory acidosis, decreased pHi, and histologic evidence of mucosal injury. Pyridoxalated hemoglobin polyoxyethylene conjugate without maltose was a superior resuscitation solution in this swine model.