Polymerized human hemoglobin with low and high oxygen affinity in trauma models

• Published in: Translational research : the journal of laboratory and clinical medicine 2023-10, Vol.260, p.83-92
• Main Authors: Muller, Cynthia R., Courelli, Vasiliki, Walser, Cynthia, Cuddington, Clayton T., Wolfe, Savannah R., Palmer, Andre F., Cabrales, Pedro
• Format: Article
• Language: English
• Subjects: Hemorrhagic shock; Oxygen carriers; Oxygen therapeutics; Polymerized hemoglobin; Red blood cell substitute; Traumatic brain injury
• ISSN: 1931-5244; 1878-1810
• DOI: 10.1016/j.trsl.2023.05.006

The present study aimed to compare the ability of tense (T) and relaxed (R) quaternary state polymerized human hemoglobin (PolyhHb) to restore hemodynamics after severe trauma in a rat model, and to assess their relative toxicity in a guinea pigs (GPs). To assess the efficacy of these PolyhHbs in restoring hemodynamics, Wistar rats were subjected to traumatic brain injury (TBI) followed by hemorrhagic shock (HS). Animals were separated into 3 groups based on the resuscitation solution: Whole blood, T-state or R-state PolyhHb, and followed for 2 hours after resuscitation. For toxicity evaluation, GPs were subjected to HS and the hypovolemic state was maintained for 50 minutes. Then, the GPs were divided randomly into 2 groups, and reperfused with T- or R-state PolyhHb. Rats resuscitated with blood and T-state PolyhHb had a higher recovery of MAP at 30 min after resuscitation when compared to R-state PolyhHb, demonstrating the greater ability of T-state PolyhHb to restore hemodynamics compared to R-state PolyhHb. Resuscitation with R-state PolyhHb in GPs increased markers of liver damage and inflammation, kidney injury and systemic inflammation compared to the T-state PolyhHb group. Finally, increased levels of cardiac damage markers, such as troponin were observed, indicating greater cardiac injury in GPs resuscitated with R-state PolyhHb. Therefore, our results showed that T-state PolyhHb exhibited superior efficacy in a model of TBI followed by HS in rats, and presented reduced vital organ toxicity in GPs, when compared to R-state PolyhHb.