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

[L’effet de l’affinité pour l’oxygène et du poids moléculaire des TOBH sur l’oxygénation et la tension artérielle chez les rats]

Gregory M.T. Hare, MD PhD^*,, Alana Harrington, HBSc^*, Elaine Liu, Jian Li Wang^*, Andrew J. Baker, MD^* and C. David Mazer, MD^*,

^* From the Department of Anesthesia, St. Michael’s Hospital, and the
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.

Address correspondence and reprint requests to: Dr. C. David Mazer, Professor, Department of Anesthesia and Physiology, University of Toronto, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada. Phone: 416-864-5825; Fax: 416-864-6014; E-mail: mazerd{at}smh.toronto.on.ca

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 P₅₀ Poly o-raffinose hemoglobin (Poly OR-Hb, P₅₀ = 70 mmHg); 2) High P₅₀ > 128 Poly OR-Hb (MW > 128 kDa, P₅₀ = 70 mmHg) and 3) Low P₅₀ > 128 Poly OR-Hb (MW >128 kDa, P₅₀ = 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 P₅₀ Poly OR-Hb group (152 ± 13 mmHg) when compared to either the Low or High P₅₀ 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.