UC San Diego

Hemorrhagic shock (HS) is a life-threating medical emergency that is caused by severe blood loss, leading to an oxygen deprivation and vital organ failures. The gold standard to hemorrhagic shock treatment remains to be the transfusion of whole blood with a balanced ratios of packed red blood cells, fresh frozen plasma and platelets. However, due to its limited availability, strict storage requirements and short shelf-life, its utility in pre-hospital and rural environments continues to be a major issue. This has prompted the development of hemoglobin-based oxygen carriers (HBOCs). Polymerized hemoglobin (PolyhHb) is a particular interest, which increases the stability of acellular hemoglobin without harming the oxygen transport properties of the protein. Early generation HBOCs failed due to effects associated with their infusion, in particular, vasoconstriction. Vasoconstriction is closely tied to being a function of molecular size. With larger PolyhHb, there has been observance of reduced adverse effects. However, it is unknown if there is a limit on the molecular weight of the PolyhHb. The objective of this study is to determine if there is an optimal size range of PolyhHb to balance out the end organ damage and the microcirculatory behavior. The experiments were performed in Golden Syrian hamsters fitted with a dorsal skinfold window chamber model to observe the acute effects of organ damage and microvascular flow post hemorrhagic shock resuscitation with polymerized hemoglobin. The results indicate that across the five formulations that were utilized, including Human Hemoglobin (hHb) and four PolyhHb with sizes ranging from 1078 kDa to 1579 kDa, it has been noticed that PolyhHb-12 achieved optimal results in comparison to lower and higher molecular size alternatives. This further validates the molecular size of HBOCs highlight an important parameter for the safety and efficacy of shock treatments.