Liposome-Encapsulated Hemoglobin Transfusion Rescues Rats Undergoing Progressive Hemodilution From Lethal Organ Hypoxia Without Scavenging Nitric Oxide

In Brief Objective: To investigate the efficacy of liposome-encapsulated hemoglobin (LHb) transfusion in rats undergoing lethal progressive hemodilution. Summary Background Data: Unlike other acellular hemoglobin-based oxygen carriers, LHb has lipid bilayer membranes that are similar to mammalian red blood cells (RBCs), which prevent hemoglobin from having any direct contact with the blood components and the endothelium. Acellular hemoglobin has a high affinity for nitric oxide (NO), and because they are reported to behave as NO scavengers, acellular hemoglobin-based oxygen carriers could have pressor effects on the peripheral vessels. During a massive hemorrhage, acellular hemoglobin caused vasoconstriction could decrease peripheral perfusion, thereby leading to diminished oxygen delivery. Methods: Rats were subjected to blood withdrawal (0.2 mL/min) with a simultaneous resuscitation using an isovolemic fluid transfusion that contained LHb, 5% albumin, or washed rat RBCs for 150 minutes (n = 15 in each group). Results: All rats transfused with LHb or RBCs were rescued from lethal progressive hemodilution, whereas none of the albumin-transfused rats survived. LHb did not affect the plasma NO metabolite levels, suggesting it was not a potent NO scavenger. LHb also improved hemodilution-induced metabolic acidosis, and reduced exaggerated neuroendocrine responses and injuries to the heart, liver, and kidney. It suppressed expression of hypoxia-inducible factor-1alpha in the liver and kidney, suggesting improvement of hypoxia at molecular response levels. However, neither transfused LHb nor RBCs improved the acute lung injury that occurs after progressive hemodilution. Conclusion: LHb transfusion is effective in rescuing rats undergoing progressive hemodilution from lethal organ hypoxia without scavenging NO. Transfusion with liposome-encapsulated hemoglobin (LHb) can rescue rats from fatal progressive hemodilution without any potent nitric oxide scavenging effects that have been seen for other hemoglobin-based oxygen carriers. LHb transfusion improves metabolic acidosis, and reduces exaggerated neuroendocrine response and injuries to the heart, liver, and kidney in rats undergoing hemodilution. LHb transfusion also suppresses the expression of hypoxia-inducible factor-1alpha in the liver and kidney.