Effect of oxygen affinity and molecular weight of HBOCs on cerebral oxygenation and blood pressure in rats

Purpose: This study assessed the effect of oxygen affinity and molecular weight (MW) of o-raffinose cross-linked hemoglobin based oxygen carriers (HBOCs) on cerebral oxygen delivery and mean arterial blood pressure (MAP) following hemorrhage and resuscitation in rats. Methods: Isoflurane anesthetized rats (n = 6-7 per group) underwent 30% hemorrhage and resuscitation with an equivalent volume of one of three different HBOCs: 1) High P-50 Poly o-raffinose hemoglobin (Poly OR-Hb, P-50 = 70 mmHg); 2) High P-50 > 128 Poly OR-Hb (MW > 128 kDa, P-50 = 70 mmHg) and 3) Low P-50 > 128 Poly OR-Hb (MW > 128 kDa, P-50 = 11 mmHg). Hippocampal cerebral tissue oxygen tension, regional cerebral blood flow (rCBF), MAP total hemoglobin concentration and arterial blood gases were measured. Data analysis by two-way ANOVA and post hoc Tukey tests determined significance (P < 0.05, mean +/- SD). Results: Hippocampal tissue oxygen tension increased in all HBOC groups following resuscitation. The rCBF remained unchanged after HBOC resuscitation in all groups. Following resuscitation, the peak MAP was higher in the High P 50 Poly OR-Hb group (152 13 mmHg) when compared to either the Low or High P 50 large MW, (> 128 kDa) HBOC group (119 15 mmHg or 127 18 respectively, P < 0.05 for both). Conclusions: O-raffinose polymerized HBOC, with or without lower MW components, maintained cerebral tissue oxygen delivery following hemorrhage and resuscitation in rats. The higher MW HBOCs showed a decrease in peak MAP which did not alter oxygen delivery. No significant effect of oxygen affinity on cerebral tissue oxygen tension or blood flow was observed.