Abstract
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.
Résumé
Objectif
Évaluer l’effet de l’affinité pour l’oxygène et du poids moléculaire (PM) des transporteurs d’oxygène à base d’hémoglobine (TOBH) avec o-raffinose sur l’apport d’oxygène cérébral et la tension artérielle moyenne (TAM) après une hémorragie et une réanimation chez des rats.
Méthode
Des rats anesthésiés à l’isoflurane (n = 6-7 par groupe) ont subi une hémorragie à 30% et une réanimation avec un volume équivalent de l’un des trois différents TOBH suivants : 1) de l’hémoglobine Poly o-raffinose à P50 élevé (Poly OR-Hb, P50 = 70 mmHg) ; 2) 128 Poly OR-Hb à P50 élevé (PM > 128 kDa, P50 = 70 mmHg) et 3) 128 Poly OR-Hb à faible P50 (PM > 128 kDa, P50 = 1 1 mmHg). La tension en oxygène du tissu cérébral hippocampique, le débit sanguin cérébral régional (DSCr), la TAM, la concentration d’hémoglobine totale et la gazométrie du sang artériel ont été mesurés. L’analyse de données, par double ANOVA et tests de Tukey ultérieur, ont permis de déterminer la valeur significative (P < 0,05, moyenne ± SD).
Résultats
La tension en oxygène du tissu hippocampique s’est accrue dans tous les groupes de TOBH après la réanimation. Le DSCr est resté le même dans tous les groupes après la réanimation avec les TOBH. Après la réanimation, la TAM était plus élevée dans le groupe Poly OR-Hb à P50 élevé (152 ± 13 mmHg) comparé au groupe de TOBH de P50 élevé et de grand PM, (> 128 kDa) (119 ± 15 mmHg ou 127 ± 18 respectivement, P < 0,05 pour les deux).
Conclusion
Les TOBH polymérisés avec o-raffinose, avec ou sans composants de faible PM, ont maintenu l’apport d’oxygène au tissu cérébral après une hémorragie et une réanimation chez des rats. Les TOBH de PM élevé ont montré une baisse de la TAM qui n’a pas nui à l’apport d’oxygène. Aucun effet significatif de l’affinité pour l’oxygène sur la tension en oxygène du tissu cérébral ou sur le débit sanguin n’a été observé.
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Supported by the Anemia Institute for Research and Education, Canadian Anesthesiologists’ Society, Physicians Services Incorporated Foundation, Hemosol LP, St. Michael’s Hospital. Dr. Hare is a recipient of the Bristol-Myers Squibb-CAS Career Scientist Award. Hemoglobin based oxygen carriers (HBOCs) were generously provided by Hemosol LP. Mississauga, ON, Canada.
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Hare, G.M.T., Harrington, A., Liu, E. et al. Effect of oxygen affinity and molecular weight of HBOCs on cerebral oxygenation and blood pressure in rats. Can J Anesth 53, 1030–1038 (2006). https://doi.org/10.1007/BF03022533
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DOI: https://doi.org/10.1007/BF03022533