Toxicity of human hemoglobin solution infused into rabbits

Area of Science:

• Biomedical research
• Toxicology
• Hematology

Background:

• Aqueous hemoglobin solutions are explored as oxygen-transporting resuscitation agents.
• Concerns exist regarding the potential toxicity of these hemoglobin-based solutions.

Purpose of the Study:

• To investigate the toxicity of aqueous human hemoglobin solutions at clinically relevant doses in a rabbit model.
• To assess whether purification methods impact hemoglobin solution toxicity.

Main Methods:

• Rabbits were infused with clinically significant doses (20%-30% blood volume) of various hemoglobin solutions (10 gm/dl).
• Preparation methods included stroma-free hemolysate, stroma-free hemoglobin, zinc-precipitated hemoglobin, and chromatographically purified hemoglobin.
• Toxicity was evaluated by observing cardiac rhythm, coagulation, tissue necrosis, hypoxia, and mortality.

Main Results:

• Hemoglobin solutions induced toxicity, including cardiac rhythm disturbances (25%), intravascular thrombi, and tissue necrosis (brain 29%, liver 25%).
• Mortality was observed in 22% of rabbits, with significantly lower arterial PO2 in deceased animals, indicating hypoxia as a likely cause of death.
• Toxicity was consistent across different purification levels of hemoglobin solutions; nonhemoglobin proteins alone showed no toxicity.

Conclusions:

• At clinically relevant doses, aqueous hemoglobin solutions exhibit significant toxicity in rabbits.
• The observed toxicity is inherent to hemoglobin itself or closely associated components, not nonhemoglobin proteins.
• These findings raise concerns about the safety of hemoglobin-based oxygen carriers for resuscitation.