Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model

Abstract

ObjectivesHemoglobin vesicles (HbVs) function as a red blood cell (RBC) substitute and are composed of purified hemoglobin encapsulated in a phospholipid bilayer membrane. The performance of HbVs as a substitute for RBC transfusions was examined in a mouse model of pneumonectomy following acute 40% exchange-transfusion with HbVs.MethodsBefore performing left pneumonectomies, 40% of the blood volume of mice was replaced with a) lactated Ringer’s solution (control), b) 5% recombinant human serum albumin (rHSA), c) mouse RBCs shed in rHSA (mRBCs/rHSA), or d) HbV suspended in rHSA (HbV/rHSA). We compared postoperative a) survival, b) functional recovery, and c) histopathological, immunohistochemical, and inflammatory responses among the study groups.ResultsIn the HbV/rHSA and mRBC/rHSA groups, all mice survived ≥7 days after pneumonectomy, whereas 100% of the control mice died within a few h and 50% of mice in the rHSA group died within 24 h after pneumonectomy. Immunohistochemical staining for hypoxia-inducible factor-1α showed that hepatic and renal hypoxic injuries were prominently mitigated by HbV and mRBCs.ConclusionsThe oxygen-carrying performance of HbV was similar to that of mRBCs, even with impaired lung functions following pneumonectomy. HbV infusion did not interfere with the recovery from surgical injury. In the near future, HbVs could be used clinically as a substitute for the perioperative transfusion of RBCs, when or where donated RBCs are not immediately available.

Immediate effects of systemic administration of normal and high O2-affinity haemoglobin vesicles as a transfusion alternative in a rat pneumonectomy model

“…The short-term to long-term effects of normal HbV infusion have been evaluated in a mouse pneumonectomy model in which 40% of circulating blood was exchanged with an HbV solution 24. All the pneumonectomised mice survived after acute isovolemic haemodilution with HbV suspended in serum albumin, although half of the mice died after albumin transfusion without oxygen carriers, similar to the results obtained in the present study.…”

Oxygen Transport during Ex Situ Machine Perfusion of Donor Livers Using Red Blood Cells or Artificial Oxygen Carriers

“…Although Hb-Vs are small in comparison to RBCs, they are large compared to macromolecules ( Figure 3 ) and accordingly do not generate a colloid osmotic pressure. The half-life of Hb-Vs is two to three days, which limits their use [ 66 , 67 ]. A few studies have reported on the use of Hb-Vs in porcine and rat MP models for livers and limbs [ 63 , 68 , 69 ].…”

Artificial Oxygen Carriers—Past, Present, and Future—a Review of the Most Innovative and Clinically Relevant Concepts

“…HbVesicles do not contribute to the colloid osmotic pressure. HbVesicles have been studied in preclinical animal blood exchange and hemorrhagic shock models and were also tested in different areas such as isolated organ perfusion, extracorporeal membrane oxygenation priming, apnoe and two-dimensional cell cultures (Kohno et al, 2017;Sakai, 2017).…”